B-Cell Lymphoma
Conditions
Keywords
Lymphoma, NHL
Brief summary
The purpose of the study is to determine the tolerability, the initial safety profile and maximum tolerated dose, and to obtain preliminary information on the antitumor activity of inotuzumab ozogamicin \[CMC-544\] in combination with rituximab in subjects with follicular, diffuse large B-Cell, or mantle cell NHL.
Interventions
DRUGinotuzumab ozogamicin
IV, 1.8 mg/m2, q4w
DRUGRituximab
rituximab 375 mg/m\^2 via IV infusion on Day 1
Sponsors
UCB Pharma
Pfizer
Study design
Allocation
NON_RANDOMIZED
Intervention model
FACTORIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Subjects with CD20 and CD22-positive, follicular or diffuse large B-cell NHL who have not responded or progressed after 1 or 2 prior therapies; or subjects with CD20 and CD22-positive intermediate/aggressive NHL (diffuse large B-cell, mantle cell, transformed follicular or follicular grade 3b NHL) who have not responded or progressed after 1 or more prior therapies and are refractory to a previous rituximab containing therapy. * Prior therapy must contain at least one course of rituximab therapy, as single agent or in combination. * Measurable disease.
Exclusion criteria
* Subjects who are candidates for other potentially curative therapies. * Subjects must not have received previous radioimmunotherapy. * Subjects who have undergone a prior bone marrow transplantation within the last 6 months.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Maximum Tolerated Dose (MTD) of Inotuzumab Ozogamicin in Combination With Rituximab (375 mg/m^2 ) | First 28-day cycle | Inotuzumab ozogamicin was dose escalated (3 to 6 evaluable participants enrolled per dose cohort) during the first 28 days after the first administration of inotuzumab ozogamicin + rituximab. Enrollment at the next dose level or enrollment of additional subjects into a cohort proceeded according to the following criteria: 0 dose-limiting toxicity (DLT) by Day 28 of first dose move to higher dose, 1 participant reporting DLT but no others in cohort by Day 28 of first dose move to higher dose, greater than 2 participants reporting DLT by Day 28 of first dose stop and prior dose level considered MTD. The worldwide medical monitor and investigators reviewed all significant study drug-related toxicities to determine if the dose escalation rules were satisfied and whether the dose escalation schedule required modification. |
| Percentage of Participants With a Treatment Emergent Adverse Event (TEAE) (Safety Population) | Protocol reporting period of from informed consent to at least 28 days after the last dose. This outcome measure time frame: From the first dose of study drug to up to 56 days after the last dose of either study drug. | A TEAE is any event that occurred after the first dose of study drug up to 56 days post the last dose of study drug (either rituximab or inotuzumab ozogamicin). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Kaplan-Meier Estimates of the Probability of Being Progression Free at 6 Months | From the first dose to 6 months after first dose | Progression Free Survival is defined as the time interval from the first dose of test article until the first date on which relapsed disease, progression, initiation of new anti-cancer treatment due to persistent/refractory disease, or death was documented, censored at the last tumor evaluation. |
| Kaplan-Meier Estimates of Overall Survival (OS) | From the first dose up to 5 years post last dose | OS was defined as the time from randomization to death due to any cause, censoring at the date of last contact. The Kaplan-Meier method was used to determine OS. 95% 2-sided confidence interval were calculated using stratified Cox proportional hazard regression. |
| Kaplan-Meier Estimates of the Probability of Survival at 6 Months | From the first dose to 6 months after first dose. | Overall Survival (OS) was defined as the time from randomization to death due to any cause, censoring at the date of last contact. The Kaplan-Meier method was used to determine OS. 95% 2-sided confidence interval were calculated using stratified Cox proportional hazard regression. |
| Kaplan-Meier Estimates of Time to Tumor Progression (TTP) | From the date of first dose of test article until the first date on which disease progression or death was documented, any of which could be reported up to 5 years post last dose. | TTP is defined as the interval from the first dose of the test article until the first date on which relapsed disease or progression, or death secondary to progression is documented, censored at the last disease assessment. Relapsed or Progressive Disease (PD) requires the following: a. Appearance of any new lesions, b. Increase by \>= 50% in the size of previously involved sites, c. \>= 50% increase in greatest diameter of any previously identified node greater than 1 cm in its short axis or in the SPD of more than one node, d. \>= 50% increase from nadir in the product diameter of any previously identified abnormal node for PRs or nonresponders, e. Enlarging spleen or liver. The Kaplan-Meier method was used to determine TTP. 95% 2-sided confidence interval were calculated using stratified Cox proportional hazard regression. |
| Kaplan-Meier Estimates of the Probability of Being Event Free at 6 Months | From enrollment to up to 6 months from 1st dose. | Time-to-Tumor Progression (TTP): is defined as the interval from the first dose of the test article until the first date on which relapsed disease or progression, or death secondary to progression is documented, censored at the last disease assessment. Relapsed or Progressive Disease (PD) requires the following: a. Appearance of any new lesions, b. Increase by \>=50% in the size of previously involved sites, c. \>= 50% increase in greatest diameter of any previously identified node greater than 1 cm in its short axis or in the SPD of more than one node, d. \>= 50% increase from nadir in the product diameter of any previously identified abnormal node for PRs or nonresponders, e. Enlarging spleen or liver. The Kaplan-Meier method was used to determineTTP. 95% 2-sided confidence interval were calculated using stratified Cox proportional hazard regression. |
| Duration of Response (CR+CRu+PR) | Time from date measurement criteria are met for CR, CRu, or PR (whichever status is recorded first) until the first date relapsed disease or date of death (whichever occurs first) is objectively documented. | Time from date measurement criteria met for CR, CRu, or PR (whichever occurred first) until first date relapsed disease/date of death. CR: Complete disappearance of all detectable clinical, radiographic evidence of disease, disease-related symptoms, normalization of NHL assignable biochemical abnormalities; lymph nodes, nodal masses regressed to normal size; spleen size regressed, not palpable on physical exam, size of other organs enlarged due to disease. CRu: CR but allows for: residual lymph node mass \>1.5 cm in greatest transverse diameter that regressed \>75% in product diameter. Individual nodes previously confluent, regressed by \>75% in their product diameters; Indeterminate bone marrow. PR: ≥50% decrease in SPD of 6 largest dominant nodes/nodal masses; No increase in size of other nodes, liver, or spleen; Splenic/hepatic nodules regressed by ≥50% in SPD; Except splenic/hepatic nodules, involvement of other organs assessable and no measurable disease present. |
| Area Under the Serum Concentration-time Profile From Time Zero Extrapolated to Infinite Time (AUCinf) of Inotuzumab Ozogamicin in Participants Receiving Inotuzumab Ozogamicin MTD + Rituximab 375 mg/m^2 on Dosing Day 30 and Day 58 | Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57; Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85 | Serum concentration of inotuzumab ozogamicin on Dosing Days 30 and 58 were measured. AUCinf of inotuzumab ozogamicin was reported. AUCinf: AUClast (area under the serum concentration-time profile for inotuzumab ozogamicin from time zero to the time of the last quantifiable concentration) +(Clast \[last quantifiable concentration\]/kel \[elimination rate constant\]) where Clast is the predicted serum concentration of inotuzumab ozogamicin at the last quantifiable timepoint estimated from the log-linear regression analysis. Study Days Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57 and Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85 correspond to Dosing Day 30 for Cycle 2 and Dosing Day 58 for Cycle 3. |
| AUClast of Inotuzumab Ozogamicin in Participants Receiving Inotuzumab Ozogamicin MTD + Rituximab 375 mg/m^2 on Dosing Day 1, Day 30 and Day 58 | Cycle 1, Days 1 (0 hour), 2 (0, 1, 4 hours), 4, 8, 10, 15, and 29; Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57; Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85 | Serum concentration of inotuzumab ozogamicin on Dosing Days 1, 30 and 58 were measured. AUC of inotuzumab ozogamicin was reported. AUClast is area under the serum concentration-time profile from time zero to the time of the Clast, using Linear/Log trapezoidal method. Study Days Cycle 1, Days 1 (0 hour), 2 (0, 1, 4 hours), 4, 8, 10, 15, and 29; Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57; and Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85 correspond to Dosing Day 1 for Cycle 1; Dosing Day 30 for Cycle 2; and Dosing Day 58 for Cycle 3. |
| Time of the Last Quantifiable Serum Concentration in a Dosing Interval (Tlast) of Inotuzumab Ozogamicin in Participants Receving Inotuzumab Ozogamicin MTD + Rituximab 375 mg/m^2 on Dosing Day 1, Day 30 and Day 58 | Cycle 1, Days 1 (0 hour), 2 (0, 1, 4 hours), 4, 8, 10, 15, and 29; Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57; Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85 | Tlast of inotuzumab ozogamicin on Dosing Days 1, 30, and 58 was reported. Tlast: Time of last quantifiable concentration of inotuzumab ozogamicin. Observed directly from data. Study Days Cycle 1, Days 1 (0 hour), 2 (0, 1, 4 hours), 4, 8, 10, 15, and 29; Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57; and Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85 correspond to Dosing Day 1 for Cycle 1; Dosing Day 30 for Cycle 2; and Dosing Day 58 for Cycle 3. |
| Area Under the Steady-state Serum Concentration-time Curve (AUCtau) of Inotuzumab Ozogamicin in Participants Receving Inotuzumab Ozogamicin MTD + Rituximab 375 mg/m^2 on Dosing Day 1, Day 30 and Day 58 | Cycle 1, Days 1 (0 hour), 2 (0, 1, 4 hours), 4, 8, 10, 15, and 29; Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57; Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85 | Steady-state serum concentrations of inotuzumab ozogamicin on Dosing Days 1, 30 and 58 were measured. AUCtau of inotuzumab ozogamicin was reported. AUCtau=AUC over dosage interval tau calculated using Linear/log trapezoidal method. Study Days Cycle 1, Days 1 (0 hour), 2 (0, 1, 4 hours), 4, 8, 10, 15, and 29; Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57; and Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85 correspond to Dosing Day 1 for Cycle 1; Dosing Day 30 for Cycle 2; and Dosing Day 58 for Cycle 3. |
| Peak Serum Concentration (Cmax) of Inotuzumab Ozogamicin in Participants Receving Inotuzumab Ozogamicin MTD + Rituximab 375 mg/m^2 on Dosing Day 1, Day 30 and Day 58 | Cycle 1, Days 1 (0 hour), 2 (0, 1, 4 hours), 4, 8, 10, 15, and 29; Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57; Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85 | Serum concentration of inotuzumab ozogamicin on Dosing Days 1, 30, and 58 were measured. Cmax of inotuzumab ozogamicin was reported. Cmax was observed directly from data. Study Days Cycle 1, Days 1 (0 hour), 2 (0, 1, 4 hours), 4, 8, 10, 15, and 29; Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57; and Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85 correspond to Dosing Day 1 for Cycle 1; Dosing Day 30 for Cycle 2; and Dosing Day 58 for Cycle 3. |
| Time to Reach Maximum Concentration (Tmax) of Inotuzumab Ozogamicin in Participants Receiving Inotuzumab Ozogamicin MTD + Rituximab 375 mg/m^2 on Dosing Day 1, Day 30 and Day 58 | Cycle 1, Days 1 (0 hour), 2 (0, 1, 4 hours), 4, 8, 10, 15, and 29; Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57; Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85 | Tmax: Time at which Cmax occurs. Observed directly from data as time of first occurrence. Study Days Cycle 1, Days 1 (0 hour), 2 (0, 1, 4 hours), 4, 8, 10, 15, and 29; Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57; and Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85 correspond to Dosing Day 1 for Cycle 1; Dosing Day 30 for Cycle 2; and Dosing Day 58 for Cycle 3. |
| Average Serum Concentration at Steady State (Cav) of Inotuzumab Ozogamicin in Participants Receiving Inotuzumab Ozogamicin MTD + Rituximab 375 mg/m^2 on Dosing Day 30 and Day 58 | Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57; Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85 | Cav: AUCtau (Area under the concentration time profile)/tau for Dosing Day 30 Cycle 2 and Dosing Day 58 Cycle 3. Study Days Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57 and Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85 correspond to Dosing Day 30 for Cycle 2 and Dosing Day 58 for Cycle 3. |
| Minimum Observed Serum Trough Concentration (Cmin) of Inotuzumab Ozogamicin in Participants Receiving Inotuzumab+Rituximab on Dosing Day 30 and Day 58 | Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57; Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85 | Cmin: Lowest concentration observed during the dosing interval tau. Observed directly from data from Dosing Day 30 for Cycle 2; and Dosing Day 58 for Cycle 3. Study Days Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57 and Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85 correspond to Dosing Day 30 for Cycle 2 and Dosing Day 58 for Cycle 3. |
| Clearance (CL) of Serum Inotuzumab Ozogamicin in Participants Receiving Inotuzumab+Rituximab on Dosing Day 30 and Day 58 | Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57; Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85 | Clearance is defined as Dose/AUCinf. Study Days Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57 and Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85 correspond to Dosing Day 30 for Cycle 2 and Dosing Day 58 for Cycle 3. |
| Steady-state Volume of Distribution (Vss) of Inotuzumab Ozogamicin in Serum in Participants Receiving Inotuzumab MTD+Rituximab 375 mg/m^2 on Dosing Day 30 and Day 58 | Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57; Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85 | Vss of inotuzumab ozogamicin on Dosing Days 30 and 58 were reported. Vss=CL\*MRT (mean residence time). Study Days Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57 and Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85 correspond to Dosing Day 30 for Cycle 2 and Dosing Day 58 for Cycle 3. |
| MRT of Inotuzumab Ozogamicin in Serum in Participants Receiving Inotuzumab Ozogamicin MTD + Rituximab 375 mg/m^2 on Dosing Day 30 and Day 58 | Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57; Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85 | MRT: AUMCinf/AUCinf - DOF (degrees of freedom)/2, where AUMCinf is the area under the first moment curve derived using the linear/log trapezoidal method, and DOF is the duration of the IV infusion dose. Study Days Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57 and Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85 correspond to Dosing Day 30 for Cycle 2 and Dosing Day 58 for Cycle 3. |
| Serum Decay Half-Life (t1/2) of Inotuzumab Ozogamicin in Participants Receiving Inotuzumab Ozogamicin MTD + Rituximab 375 mg/m^2 on Dosing Day 30 and Day 58 | Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57; Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85 | Termnial half-life (t½): Loge(2)/kel, where kel is the terminal phase rate constant calculated by a linear regression of the log-linear concentration-time curve. Study Days Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57 and Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85 correspond to Dosing Day 30 for Cycle 2 and Dosing Day 58 for Cycle 3. |
| AUCinf of Total Calicheamicin (Conjugated + Unconjugated) in Participants Receiving Inotuzumab Ozogamicin MTD + Rituximab 375 mg/m^2 on Dosing Day 30 and Day 58 | Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57; Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85 | AUCinf: AUClast+(Clast/kel) where Clast is the predicted serum concentration at the last quantifiable timepoint estimated from the log-linear regression analysis. Study Days Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57 and Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85 correspond to Dosing Day 30 for Cycle 2 and Dosing Day 58 for Cycle 3. |
| AUClast of Total Calicheamicin (Conjugated Plus Unconjugated) in Participants Receiving Inotuzumab Ozogamicin MTD + Rituximab 375 mg/m^2 on Dosing Day 1, Day 30 and Day 58 | Cycle 1, Days 1 (0 hour), 2 (0, 1, 4 hours), 4, 8, 10, 15, and 29; Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57; Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85 | AUClast: AUC over dosage interval through last measurable time point, Tlast, using Linear/Log trapezoidal method. Study Days Cycle 1, Days 1 (0 hour), 2 (0, 1, 4 hours), 4, 8, 10, 15, and 29; Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57; and Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85 correspond to Dosing Day 1 for Cycle 1; Dosing Day 30 for Cycle 2; and Dosing Day 58 for Cycle 3. |
| Time of the Last Quantifiable Concentration in a Dosing Interval (Tlast) of Total Calicheamicin (Conjugated Plus Unconjugated) in Participants Receiving Inotuzumab Ozogamicin MTD + Rituximab 375 mg/m^2 on Dosing Day 1, Day 30 and Day 58 | Cycle 1, Days 1 (0 hour), 2 (0, 1, 4 hours), 4, 8, 10, 15, and 29; Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57; Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85 | Tlast: Time of last quantifiable concentration. Observed directly from data. Study Days Cycle 1, Days 1 (0 hour), 2 (0, 1, 4 hours), 4, 8, 10, 15, and 29; Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57; and Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85 correspond to Dosing Day 1 for Cycle 1; Dosing Day 30 for Cycle 2; and Dosing Day 58 for Cycle 3. |
| Area Under the Steady-state Serum Concentration-time Curve (AUCtau) for Total Calicheamicin (Conjugated Plus Unconjugated) in Participants Receiving Inotuzumab Ozogamicin MTD + Rituximab 375 mg/m^2 on Dosing Day 1, Day 30, and Day 58 | Cycle 1, Days 1 (0 hour), 2 (0, 1, 4 hours), 4, 8, 10, 15, and 29; Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57; Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85 | AUCtau=AUC over dosage interval tau calculated using Linear/log trapezoidal method. Study Days Cycle 1, Days 1 (0 hour), 2 (0, 1, 4 hours), 4, 8, 10, 15, and 29; Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57; and Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85 correspond to Dosing Day 1 for Cycle 1; Dosing Day 30 for Cycle 2; and Dosing Day 58 for Cycle 3. |
| Peak Serum Concentration (Cmax) of Total Calicheamicin (Conjugated Plus Unconjugated) in Participants Receiving Inotuzumab Ozogamicin MTD + Rituximab 375 mg/m^2 on Dosing Day 1, Day 30 and Day 58 | Cycle 1, Days 1 (0 hour), 2 (0, 1, 4 hours), 4, 8, 10, 15, and 29; Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57; Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85 | Cmax: Observed directly from data Study Days Cycle 1, Days 1 (0 hour), 2 (0, 1, 4 hours), 4, 8, 10, 15, and 29; Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57; and Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85 correspond to Dosing Day 1 for Cycle 1; Dosing Day 30 for Cycle 2; and Dosing Day 58 for Cycle 3. |
| Time of Observed Maximum Concentration (Tmax) of Total Calicheamicin (Conjugated+Unconjugated) in Participants Receiving Inotuzumab Ozogamicin MTD + Rituximab 375 mg/m^2 on Dosing Day 1, Day 30 and Day 58 | Cycle 1, Days 1 (0 hour), 2 (0, 1, 4 hours), 4, 8, 10, 15, and 29; Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57; Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85 | Tmax: Time at which Cmax occurs. Observed directly from data as time of first occurrence. Study Days Cycle 1, Days 1 (0 hour), 2 (0, 1, 4 hours), 4, 8, 10, 15, and 29; Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57; and Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85 correspond to Dosing Day 1 for Cycle 1; Dosing Day 30 for Cycle 2; and Dosing Day 58 for Cycle 3. |
| Average Serum Concentration (Cav) of Total Calicheamicin (Conjugated Plus Unconjugated) in Participants Receiving Inotuzumab Ozogamicin MTD + Rituximab 375 mg/m^2 on Dosing Day 30 and Day 58 | Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57; Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85 | Cav: AUCtau/tau for Dosing Day 30 Cycle 2 and Dosing Day 58 Cycle 3. Study Days Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57 and Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85 correspond to Dosing Day 30 for Cycle 2 and Dosing Day 58 for Cycle 3. |
| Minimum Observed Serum Trough Concentration (Cmin) of Total Calicheamicin (Conjugated Plus Unconjugated) in Participants Receiving Inotuzumab Ozogamicin MTD + Rituximab 375 mg/m^2 on Dosing Day 30 and Day 58 | Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57; Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85 | Cmin: Lowest concentration observed during the dosing interval tau. Observed directly from data from Day 30 for Cycle 2; and Day 58 for Cycle 3. Study Days Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57 and Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85 correspond to Dosing Day 30 for Cycle 2 and Dosing Day 58 for Cycle 3. |
| Clearance (CL) of Total Calicheamicin (Conjugated Plus Unconjugated) in Participants Receiving Inotuzumab Ozogamicin MTD + Rituximab 375 mg/m^2 on Dosing Day 30 and Day 58 | Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57; Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85 | Clearance defined as Dose/AUCinf. Corresponds to Dosing Day 30 for Cycle 2 and dosing Day 58 for Cycle 3. Study Days Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57 and Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85 correspond to Dosing Day 30 for Cycle 2 and Dosing Day 58 for Cycle 3. |
| Steady-state Volume (Vss) of Total Calicheamicin (Conjugated Plus Unconjugated) Distribution in Participants Receiving Inotuzumab Ozogamicin MTD + Rituximab 375 mg/m^2 on Dosing Day 30 and Day 58 | Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57; Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85 | Vss: Steady-state volume of distribution CL\*MRT of inotuzumab ozogamicin Day 30 for Cycle 2; and Day 58 for Cycle 3. Study Days Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57 and Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85 correspond to Dosing Day 30 for Cycle 2 and Dosing Day 58 for Cycle 3. |
| Mean Residence Time (MRT) of Total Calicheamicin (Conjugated Plus Unconjugated) in Participants Receiving Inotuzumab Ozogamicin MTD + Rituximab 375 mg/m^2 on Dosing Day 30 and Day 58 | Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57; Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85 | MRT: AUMCinf/AUCinf - DOF/2, where AUMCinf is the area under the first moment curve derived using the linear/log trapezoidal method, and DOF is the duration of the IV infusion dose. Study Days Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57 and Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85 correspond to Dosing Day 30 for Cycle 2 and Dosing Day 58 for Cycle 3. |
| Serum Decay Half-Life (t1/2) of Total Calicheamicin (Conjugated Plus Unconjugated) in Participants Receiving Inotuzumab Ozogamicin MTD + Rituximab 375 mg/m^2 on Dosing Day 30 and Day 58 | Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57; Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85 | Termnial half-life (t½): Loge(2)/kel, where kel is the terminal phase rate constant calculated by a linear regression of the log-linear concentration-time curve. Study Days Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57 and Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85 correspond to Dosing Day 30 for Cycle 2 and Dosing Day 58 for Cycle 3. |
| Area Under the Steady-state Serum Concentration-time Curve (AUClast) of Unconjugated Calicheamicin in Participants Receiving Inotuzumab Ozogamicin MTD + Rituximab 375 mg/m^2 on Dosing Day 1, Day 30 and Day 58 | Cycle 1, Days 1 (0 hour), 2 (0, 1, 4 hours), 4, 8, 10, 15, and 29; Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57; Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85 | AUClast: AUC over dosage interval through last measurable time point, Tlast, using Linear/Log trapezoidal method. Study Days Cycle 1, Days 1 (0 hour), 2 (0, 1, 4 hours), 4, 8, 10, 15, and 29; Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57; and Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85 correspond to Dosing Day 1 for Cycle 1; Dosing Day 30 for Cycle 2; and Dosing Day 58 for Cycle 3. |
| Time of the Last Quantifiable Concentration in a Dosing Interval (Tlast) of Unconjugated Calicheamicin in Participants Receiving Inotuzumab Ozogamicin MTD + Rituximab 375 mg/m^2 on Dosing Day 1, Day 30 and Day 58 | Cycle 1, Days 1 (0 hour), 2 (0, 1, 4 hours), 4, 8, 10, 15, and 29; Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57; Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85 | Tlast: Time of last quantifiable concentration. Observed directly from data. Study Days Cycle 1, Days 1 (0 hour), 2 (0, 1, 4 hours), 4, 8, 10, 15, and 29; Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57; and Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85 correspond to Dosing Day 1 for Cycle 1; Dosing Day 30 for Cycle 2; and Dosing Day 58 for Cycle 3. |
| Peak Serum Concentration (Cmax) of Unconjugated Calicheamicin in Participants Receiving Inotuzumab Ozogamicin MTD + Rituximab 375 mg/m^2 on Dosing Day 1, Day 30 and Day 58 | Cycle 1, Days 1 (0 hour), 2 (0, 1, 4 hours), 4, 8, 10, 15, and 29; Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57; Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85 | Cmax: Observed directly from data Study Days Cycle 1, Days 1 (0 hour), 2 (0, 1, 4 hours), 4, 8, 10, 15, and 29; Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57; and Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85 correspond to Dosing Day 1 for Cycle 1; Dosing Day 30 for Cycle 2; and Dosing Day 58 for Cycle 3. |
| Time of Observed Maximum Concentration (Tmax) of Unconjugated Calicheamicin in Participants Receiving Inotuzumab Ozogamicin + Rituximab on Dosing Day 1, Day 30 and Day 58 | Cycle 1, Days 1 (0 hour), 2 (0, 1, 4 hours), 4, 8, 10, 15, and 29; Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57; Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85 | Tmax: Time at which Cmax occurs. Observed directly from data as time of first occurrence. Study Days Cycle 1, Days 1 (0 hour), 2 (0, 1, 4 hours), 4, 8, 10, 15, and 29; Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57; and Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85 correspond to Dosing Day 1 for Cycle 1; Dosing Day 30 for Cycle 2; and Dosing Day 58 for Cycle 3. |
| Average Serum Concentration (Cav) of Inotuzumab Ozogamicin Antibody in Participants Receiving Inotuzumab Ozogamicin MTD + Rituximab 375 mg/m^2 on Dosing Day 30 and Day 58 | Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57; Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85 | Cav: AUCtau/tau for Dosing Day 30 Cycle 2 and Dosing Day 58 Cycle 3. Study Days Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57 and Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85 correspond to Dosing Day 30 for Cycle 2 and Dosing Day 58 for Cycle 3. |
| Minimum Observed Serum Trough Concentration (Cmin) of Unconjugated Calicheamicin in Participants Receiving Inotuzumab Ozogamicin+Rituximab on Dosing Day 30 and Day 58 | Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57; Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85 | Cmin: Lowest concentration observed during the dosing interval tau. Study Days Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57 and Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85 correspond to Dosing Day 30 for Cycle 2 and Dosing Day 58 for Cycle 3. |
| Area Under the Serum Concentration-time Profile From Time Zero Extrapolated to Infinite Time (AUCinf) of Inotuzumab Ozogamicin Antibody in Participants Receiving Inotuzumab Ozogamicin MTD + Rituximab 375 mg/m2 on Dosing Day 30 and Day 58 | Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57; Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85 | AUCinf: AUClast+(Clast/kel) where Clast is the predicted serum concentration at the last quantifiable timepoint estimated from the log-linear regression analysis. Study Days Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57 and Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85 correspond to Dosing Day 30 for Cycle 2 and Dosing Day 58 for Cycle 3. |
| Area Under the Steady-state Concentration-time Curve (AUClast) of Serum Inotuzumab Ozogamicin Antibody in Participants Receiving Inotuzumab Ozogamicin MTD + Rituximab 375 mg/m^2 on Dosing Day 1, Day 30 and Day 58 | Cycle 1, Days 1 (0 hour), 2 (0, 1, 4 hours), 4, 8, 10, 15, and 29; Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57; Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85 | AUClast: AUC over dosage interval through last measurable time point, Tlast, using Linear/Log trapezoidal method. Study Days Cycle 1, Days 1 (0 hour), 2 (0, 1, 4 hours), 4, 8, 10, 15, and 29; Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57; and Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85 correspond to Dosing Day 1 for Cycle 1; Dosing Day 30 for Cycle 2; and Dosing Day 58 for Cycle 3. |
| Time of the Last Quantifiable Concentration in a Dosing Interval (Tlast) of Serum Inotuzumab Ozogamicin Antibody in Participants Receiving Inotuzumab Ozogamicin MTD + Rituximab 375 mg/m^2 on Dosing Day 1, Day 30 and Day 58 | Cycle 1, Days 1 (0 hour), 2 (0, 1, 4 hours), 4, 8, 10, 15, and 29; Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57; Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85 | Tlast: Time of last quantifiable concentration. Observed directly from data. Study Days Cycle 1, Days 1 (0 hour), 2 (0, 1, 4 hours), 4, 8, 10, 15, and 29; Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57; and Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85 correspond to Dosing Day 1 for Cycle 1; Dosing Day 30 for Cycle 2; and Dosing Day 58 for Cycle 3. |
| Serum Decay Half-Life (t1/2) of Inotuzumab Ozogamicin Antibody in Participants Receiving Inotuzumab Ozogamicin MTD + Rituximab on Dosing Day 30 and Day 58 | Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57; Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85 | Termnial half-life (t½): Loge(2)/kel, where kel is the terminal phase rate constant calculated by a linear regression of the log-linear concentration-time curve. Study Days Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57 and Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85 correspond to Dosing Day 30 for Cycle 2 and Dosing Day 58 for Cycle 3. |
| Area Under the Steady-state Serum Concentration-time Curve (AUCtau) of Inotuzumab Ozogamicin Antibody in Participants Receiving Inotuzumab Ozogamicin MTD+ Rituximab 375 mg/m^2 on Dosing Day 1, Day 30, and Day 58 | Cycle 1, Days 1 (0 hour), 2 (0, 1, 4 hours), 4, 8, 10, 15, and 29; Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57; Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85 | AUCtau=AUC over dosage interval tau calculated using Linear/log trapezoidal method. Study Days Cycle 1, Days 1 (0 hour), 2 (0, 1, 4 hours), 4, 8, 10, 15, and 29; Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57; and Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85 correspond to Dosing Day 1 for Cycle 1; Dosing Day 30 for Cycle 2; and Dosing Day 58 for Cycle 3. |
| Percentage of Participants With Complete Response (CR), Unconfirmed CR (CRu), or Partial Response (PR) | Approximately every 2 (during treatment) or 3 (during follow-up) to 6 months for up to 5 years from 1st dose | CR: a. Complete disappearance of all detectable clinical and radiographic evidence of disease, disease-related symptoms, and normalization of NHL assignable biochemical abnormalities ; b. lymph nodes and nodal masses must have regressed to normal size; c. Spleen regressed in size and not palpable on physical exam, size of other organs enlarged due to disease decreased in size; d. Repeat bone marrow infiltrate clear. CRu: CR but allows for a. Residual lymph node mass \>1.5 cm in greatest transverse diameter has regressed by more than 75% in diameter. Individual nodes that were previously confluent regressed more than 75 % in their product diameters; b. Indeterminate bone marrow. PR: a. ≥50 % decrease in product of the diameters (SPD) of the 6 largest dominant nodes or nodal masses; b. No increase in size of other nodes, liver, or spleen, c. Liver or spleen nodules regressed ≥50% in the SPD; d. Other organs usually assessable, no measurable disease present. |
| Time to Reach Maximum Concentration (Tmax) of Serum Inotuzumab Ozogamicin Antibody in Participants Receiving Inotuzumab Ozogamicin MTD + Rituximab 375 mg/m^2 on Dosing Day 1, Day 30 and Day 58 | Cycle 1, Days 1 (0 hour), 2 (0, 1, 4 hours), 4, 8, 10, 15, and 29; Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57; Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85 | Tmax: Time at which Cmax occurs. Observed directly from data as time of first occurrence. Study Days Cycle 1, Days 1 (0 hour), 2 (0, 1, 4 hours), 4, 8, 10, 15, and 29; Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57; and Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85 correspond to Dosing Day 1 for Cycle 1; Dosing Day 30 for Cycle 2; and Dosing Day 58 for Cycle 3. |
| Minimum Observed Serum Trough Concentration (Cmin) of Inotuzumab Ozogamicin Antibody in Participants Receiving Inotuzumab MTD + Rituximab 375 mg/m^2 on Dosing Day 30 and Day 58 | Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57; Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85 | Cmin: Lowest concentration observed during the dosing interval tau. Study Days Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57 and Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85 correspond to Dosing Day 30 for Cycle 2 and Dosing Day 58 for Cycle 3. |
| Clearance (CL) of Serum Inotuzumab Ozogamicin Antibody in Participants Receiving Inotuzumab Ozogamicin MTD + Rituximab 375 mg/m^2 on Dosing Day 30 and Day 58 | Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57; Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85 | Clearance defined as Dose/AUCinf. Study Days Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57 and Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85 correspond to Dosing Day 30 for Cycle 2 and Dosing Day 58 for Cycle 3. |
| Steady-state Volume (Vss) of Inotuzumab Ozogamicin Antibody Distribution in Participants Receiving Inotuzumab Ozogamicin MTD + Rituximab 375 mg/m^2 on Dosing Day 30 and Day 58 | Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57; Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85 | Vss: Steady-state volume of distribution CL\*MRT of inotuzumab ozogamicin Day 30 for Cycle 2; and Day 58 for Cycle 3. Study Days Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57 and Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85 correspond to Dosing Day 30 for Cycle 2 and Dosing Day 58 for Cycle 3. |
| Peak Concentration (Cmax) of Serum Inotuzumab Ozogamicin Antibody in Participants Receiving Inotuzumab Ozogamicin MTD + Rituximab 375 mg/m^2 on Dosing Day 1, Day 30 and Day 58 | Cycle 1, Days 1 (0 hour), 2 (0, 1, 4 hours), 4, 8, 10, 15, and 29; Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57; Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85 | Cmax: Observed directly from data Study Days Cycle 1, Days 1 (0 hour), 2 (0, 1, 4 hours), 4, 8, 10, 15, and 29; Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57; and Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85 correspond to Dosing Day 1 for Cycle 1; Dosing Day 30 for Cycle 2; and Dosing Day 58 for Cycle 3. |
| Kaplan-Meier Estimates of Progression Free Survival (PFS) | From the date of first dose of test article until the first date on which disease progression or death was documented or new anticancer start, any of which could be reported up to 5 years post last dose | The Kaplan-Meier method was used to determine PFS. 95% 2-sided confidence interval were calculated using stratified Cox proportional hazard regression. Relapsed or Progressive Disease (PD) requires the following: a. Appearance of any new lesions, b. Increase by \>= 50% in the size of previously involved sites, c. \>= 50% increase in greatest diameter of any previously identified node greater than 1 cm in its short axis or in the SPD of more than one node, d. \>= 50% increase from nadir in the product diameter of any previously identified abnormal node for PRs or nonresponders, e. Enlarging spleen or liver. |
Countries
Australia, Belgium, France, Germany, Hong Kong, Italy, Netherlands, Poland, South Korea, Spain, Switzerland, United Kingdom, United States
Participant flow
Recruitment details
A Open-Label, Phase 1/2 Study of CMC-544 (Inotuzumab Ozogamicin) in Combination With Rituximab in Subjects
Pre-assignment details
Eligible Subjects were Randomly Assigned to Study Treatments
Participants by arm
| Arm | Count |
|---|---|
| INOTUZUMAB OZOGAMICIN 0.8 MG/M^2 + RITUXIMAB 375 MG/M^2 Participants received rituximab 375 mg/m\^2 via IV infusion on Day 1 and inotuzumab ozogamicin 0.8 mg/m\^2 via IV infusion on Day 2 of each 28-day cycle for up to 8 cycles unless there was evidence of progressive disease, unacceptable toxicity, or the participant refused further treatment. | 5 |
| INOTUZUMAB OZOGAMICIN 1.3 MG/M^2 + RITUXIMAB 375 MG/M^2 Participants received rituximab 375 mg/m\^2 via IV infusion on Day 1 and inotuzumab ozogamicin 1.3 mg/m\^2 via IV infusion on Day 2 of each 28-day cycle for up to 8 cycles unless there was evidence of progressive disease, unacceptable toxicity, or the participant refused further treatment. | 3 |
| INOTUZUMAB OZOGAMICIN 1.8 MG/M^2 + RITUXIMAB 375 MG/M^2 Participants received rituximab 375 mg/m\^2 via IV infusion on Day 1 and inotuzumab ozogamicin 1.8 mg/m\^2 via IV infusion on Day 2 of each 28-day cycle for up to 8 cycles unless there was evidence of progressive disease, unacceptable toxicity, or the participant refused further treatment. | 7 |
| INOTUZUMAB OZOGAMICIN MTD + RITUXIMAB 375 MG/M^2 (FOLLICULAR) Participants received the MTD determined in the dose escalation phase; MTD determination in the dose escalation phase was based on toxicities during the 1st cycle. Participants with follicular lymphoma received rituximab 375 mg/m\^2 via IV infusion on Day 1 and the MTD of inotuzumab ozogamicin (1.8 mg/m\^2) via IV infusion on Day 2 of each 28-day cycle for up to 8 cycles unless there was evidence of progressive disease, unacceptable toxicity, or the participant refused further treatment. | 34 |
| INOTUZUMAB OZOGAMICIN MTD + RITUXIMAB 375 MG/M^2 (DLBCL) Participants received the MTD determined in the dose escalation phase; MTD determination in the dose escalation phase was based on toxicities during the 1st cycle. Participants with DLBCL received rituximab 375 mg/m\^2 via IV infusion on Day 1 and the MTD of inotuzumab ozogamicin (1.8 mg/m\^2) via IV infusion on Day 2 of each 28-day cycle for up to 8 cycles unless there was evidence of progressive disease, unacceptable toxicity, or the participant refused further treatment. | 40 |
| INOTUZUMAB OZOGAMICIN MTD + RITUXIMAB 375 MG/M^2 (REFRACTORY) Participants received the MTD determined in the dose escalation phase; MTD determination in the dose escalation phase was based on toxicities during the 1st cycle. Participants with either refractory aggressive or intermediate B-cell NHL received rituximab 375 mg/m\^2 via IV infusion on Day 1 and the MTD of inotuzumab ozogamicin (1.8 mg/m\^2) via IV infusion on Day 2 of each 28-day cycle for up to 8 cycles unless there was evidence of progressive disease, unacceptable toxicity, or the participant refused further treatment. | 30 |
| Total | 119 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 |
|---|---|---|---|---|---|---|---|
| Overall Study | Death | 3 | 1 | 4 | 6 | 18 | 19 |
| Overall Study | Lost to Follow-up | 0 | 0 | 0 | 0 | 3 | 1 |
| Overall Study | Other - site closure | 0 | 0 | 0 | 1 | 1 | 1 |
| Overall Study | Other - Unspecified | 0 | 0 | 0 | 0 | 3 | 1 |
| Overall Study | Physician Decision | 0 | 0 | 0 | 0 | 1 | 0 |
| Overall Study | Withdrawal by Subject | 0 | 0 | 0 | 3 | 1 | 4 |
Baseline characteristics
| Characteristic | INOTUZUMAB OZOGAMICIN 0.8 MG/M^2 + RITUXIMAB 375 MG/M^2 | INOTUZUMAB OZOGAMICIN 1.3 MG/M^2 + RITUXIMAB 375 MG/M^2 | INOTUZUMAB OZOGAMICIN 1.8 MG/M^2 + RITUXIMAB 375 MG/M^2 | INOTUZUMAB OZOGAMICIN MTD + RITUXIMAB 375 MG/M^2 (FOLLICULAR) | INOTUZUMAB OZOGAMICIN MTD + RITUXIMAB 375 MG/M^2 (DLBCL) | INOTUZUMAB OZOGAMICIN MTD + RITUXIMAB 375 MG/M^2 (REFRACTORY) | Total |
|---|---|---|---|---|---|---|---|
| Age, Continuous | 63.4 Years STANDARD_DEVIATION 10.9 | 65.7 Years STANDARD_DEVIATION 0.6 | 60.7 Years STANDARD_DEVIATION 9.6 | 61.7 Years STANDARD_DEVIATION 12.2 | 67.2 Years STANDARD_DEVIATION 13 | 55.5 Years STANDARD_DEVIATION 15.8 | 62.1 Years STANDARD_DEVIATION 13.7 |
| Sex: Female, Male Female | 2 Participants | 1 Participants | 1 Participants | 18 Participants | 17 Participants | 9 Participants | 48 Participants |
| Sex: Female, Male Male | 3 Participants | 2 Participants | 6 Participants | 16 Participants | 23 Participants | 21 Participants | 71 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 5 / 5 | 3 / 3 | 7 / 7 | 34 / 34 | 39 / 40 | 30 / 30 |
| serious Total, serious adverse events | 1 / 5 | 0 / 3 | 1 / 7 | 9 / 34 | 12 / 40 | 5 / 30 |
Outcome results
Primary
Maximum Tolerated Dose (MTD) of Inotuzumab Ozogamicin in Combination With Rituximab (375 mg/m^2 )
Inotuzumab ozogamicin was dose escalated (3 to 6 evaluable participants enrolled per dose cohort) during the first 28 days after the first administration of inotuzumab ozogamicin + rituximab. Enrollment at the next dose level or enrollment of additional subjects into a cohort proceeded according to the following criteria: 0 dose-limiting toxicity (DLT) by Day 28 of first dose move to higher dose, 1 participant reporting DLT but no others in cohort by Day 28 of first dose move to higher dose, greater than 2 participants reporting DLT by Day 28 of first dose stop and prior dose level considered MTD. The worldwide medical monitor and investigators reviewed all significant study drug-related toxicities to determine if the dose escalation rules were satisfied and whether the dose escalation schedule required modification.
Time frame: First 28-day cycle
Population: Intent-To-Treat (ITT) Population: All participants included in the intended dose scheme. One additional participant was enrolled over the 6 planned participants in 1.8 mg/m\^2 dose cohort because 1 participant was unevaluable for MTD evaluations.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| INOTUZUMAB OZOGAMICIN + RITUXIMAB 375 MG/M^2 | Maximum Tolerated Dose (MTD) of Inotuzumab Ozogamicin in Combination With Rituximab (375 mg/m^2 ) | 1.8 mg/m^2 |
Primary
Percentage of Participants With a Treatment Emergent Adverse Event (TEAE) (Safety Population)
A TEAE is any event that occurred after the first dose of study drug up to 56 days post the last dose of study drug (either rituximab or inotuzumab ozogamicin).
Time frame: Protocol reporting period of from informed consent to at least 28 days after the last dose. This outcome measure time frame: From the first dose of study drug to up to 56 days after the last dose of either study drug.
Population: Safety population: All participants receiving at least 1 dose of inotuzumab ozogamicin or rituximab.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| INOTUZUMAB OZOGAMICIN + RITUXIMAB 375 MG/M^2 | Percentage of Participants With a Treatment Emergent Adverse Event (TEAE) (Safety Population) | % participants with dose reduction due to TEAE | 0 Percentage of participants |
| INOTUZUMAB OZOGAMICIN + RITUXIMAB 375 MG/M^2 | Percentage of Participants With a Treatment Emergent Adverse Event (TEAE) (Safety Population) | % participants for study drug stopped temporarily | 20.0 Percentage of participants |
| INOTUZUMAB OZOGAMICIN + RITUXIMAB 375 MG/M^2 | Percentage of Participants With a Treatment Emergent Adverse Event (TEAE) (Safety Population) | % participants with Grade 3 or 4 TEAE | 80.0 Percentage of participants |
| INOTUZUMAB OZOGAMICIN + RITUXIMAB 375 MG/M^2 | Percentage of Participants With a Treatment Emergent Adverse Event (TEAE) (Safety Population) | % participants with serious TEAE | 20.0 Percentage of participants |
| INOTUZUMAB OZOGAMICIN + RITUXIMAB 375 MG/M^2 | Percentage of Participants With a Treatment Emergent Adverse Event (TEAE) (Safety Population) | % participants for study drug discontinuation | 0 Percentage of participants |
| INOTUZUMAB OZOGAMICIN + RITUXIMAB 375 MG/M^2 | Percentage of Participants With a Treatment Emergent Adverse Event (TEAE) (Safety Population) | % participants with Grade 5 TEAE | 20.0 Percentage of participants |
| INOTUZUMAB OZOGAMICIN + RITUXIMAB 375 MG/M^2 | Percentage of Participants With a Treatment Emergent Adverse Event (TEAE) (Safety Population) | % participants with a TEAE | 100 Percentage of participants |
| INOTUZUMAB OZOGAMICIN 1.3 MG/M^2 + RITUXIMAB 375 MG/M^2 | Percentage of Participants With a Treatment Emergent Adverse Event (TEAE) (Safety Population) | % participants for study drug stopped temporarily | 0 Percentage of participants |
| INOTUZUMAB OZOGAMICIN 1.3 MG/M^2 + RITUXIMAB 375 MG/M^2 | Percentage of Participants With a Treatment Emergent Adverse Event (TEAE) (Safety Population) | % participants with dose reduction due to TEAE | 0 Percentage of participants |
| INOTUZUMAB OZOGAMICIN 1.3 MG/M^2 + RITUXIMAB 375 MG/M^2 | Percentage of Participants With a Treatment Emergent Adverse Event (TEAE) (Safety Population) | % participants with Grade 3 or 4 TEAE | 66.7 Percentage of participants |
| INOTUZUMAB OZOGAMICIN 1.3 MG/M^2 + RITUXIMAB 375 MG/M^2 | Percentage of Participants With a Treatment Emergent Adverse Event (TEAE) (Safety Population) | % participants with a TEAE | 100 Percentage of participants |
| INOTUZUMAB OZOGAMICIN 1.3 MG/M^2 + RITUXIMAB 375 MG/M^2 | Percentage of Participants With a Treatment Emergent Adverse Event (TEAE) (Safety Population) | % participants with Grade 5 TEAE | 0 Percentage of participants |
| INOTUZUMAB OZOGAMICIN 1.3 MG/M^2 + RITUXIMAB 375 MG/M^2 | Percentage of Participants With a Treatment Emergent Adverse Event (TEAE) (Safety Population) | % participants for study drug discontinuation | 33.3 Percentage of participants |
| INOTUZUMAB OZOGAMICIN 1.3 MG/M^2 + RITUXIMAB 375 MG/M^2 | Percentage of Participants With a Treatment Emergent Adverse Event (TEAE) (Safety Population) | % participants with serious TEAE | 0 Percentage of participants |
| INOTUZUMAB OZOGAMICIN 1.8 MG/M^2 + RITUXIMAB 375 MG/M^2 | Percentage of Participants With a Treatment Emergent Adverse Event (TEAE) (Safety Population) | % participants with serious TEAE | 14.3 Percentage of participants |
| INOTUZUMAB OZOGAMICIN 1.8 MG/M^2 + RITUXIMAB 375 MG/M^2 | Percentage of Participants With a Treatment Emergent Adverse Event (TEAE) (Safety Population) | % participants with Grade 3 or 4 TEAE | 71.4 Percentage of participants |
| INOTUZUMAB OZOGAMICIN 1.8 MG/M^2 + RITUXIMAB 375 MG/M^2 | Percentage of Participants With a Treatment Emergent Adverse Event (TEAE) (Safety Population) | % participants for study drug discontinuation | 28.6 Percentage of participants |
| INOTUZUMAB OZOGAMICIN 1.8 MG/M^2 + RITUXIMAB 375 MG/M^2 | Percentage of Participants With a Treatment Emergent Adverse Event (TEAE) (Safety Population) | % participants with dose reduction due to TEAE | 14.3 Percentage of participants |
| INOTUZUMAB OZOGAMICIN 1.8 MG/M^2 + RITUXIMAB 375 MG/M^2 | Percentage of Participants With a Treatment Emergent Adverse Event (TEAE) (Safety Population) | % participants for study drug stopped temporarily | 42.9 Percentage of participants |
| INOTUZUMAB OZOGAMICIN 1.8 MG/M^2 + RITUXIMAB 375 MG/M^2 | Percentage of Participants With a Treatment Emergent Adverse Event (TEAE) (Safety Population) | % participants with a TEAE | 100 Percentage of participants |
| INOTUZUMAB OZOGAMICIN 1.8 MG/M^2 + RITUXIMAB 375 MG/M^2 | Percentage of Participants With a Treatment Emergent Adverse Event (TEAE) (Safety Population) | % participants with Grade 5 TEAE | 0 Percentage of participants |
| INOTUZUMAB OZOGAMICIN MTD + RITUXIMAB 375 MG/M^2 (FOLLICULAR) | Percentage of Participants With a Treatment Emergent Adverse Event (TEAE) (Safety Population) | % participants for study drug stopped temporarily | 44.1 Percentage of participants |
| INOTUZUMAB OZOGAMICIN MTD + RITUXIMAB 375 MG/M^2 (FOLLICULAR) | Percentage of Participants With a Treatment Emergent Adverse Event (TEAE) (Safety Population) | % participants with Grade 3 or 4 TEAE | 67.6 Percentage of participants |
| INOTUZUMAB OZOGAMICIN MTD + RITUXIMAB 375 MG/M^2 (FOLLICULAR) | Percentage of Participants With a Treatment Emergent Adverse Event (TEAE) (Safety Population) | % participants for study drug discontinuation | 61.8 Percentage of participants |
| INOTUZUMAB OZOGAMICIN MTD + RITUXIMAB 375 MG/M^2 (FOLLICULAR) | Percentage of Participants With a Treatment Emergent Adverse Event (TEAE) (Safety Population) | % participants with dose reduction due to TEAE | 14.7 Percentage of participants |
| INOTUZUMAB OZOGAMICIN MTD + RITUXIMAB 375 MG/M^2 (FOLLICULAR) | Percentage of Participants With a Treatment Emergent Adverse Event (TEAE) (Safety Population) | % participants with a TEAE | 100 Percentage of participants |
| INOTUZUMAB OZOGAMICIN MTD + RITUXIMAB 375 MG/M^2 (FOLLICULAR) | Percentage of Participants With a Treatment Emergent Adverse Event (TEAE) (Safety Population) | % participants with Grade 5 TEAE | 0 Percentage of participants |
| INOTUZUMAB OZOGAMICIN MTD + RITUXIMAB 375 MG/M^2 (FOLLICULAR) | Percentage of Participants With a Treatment Emergent Adverse Event (TEAE) (Safety Population) | % participants with serious TEAE | 26.5 Percentage of participants |
| INOTUZUMAB OZOGAMICIN MTD + RITUXIMAB 375 MG/M^2 (DLBCL) | Percentage of Participants With a Treatment Emergent Adverse Event (TEAE) (Safety Population) | % participants with serious TEAE | 30.0 Percentage of participants |
| INOTUZUMAB OZOGAMICIN MTD + RITUXIMAB 375 MG/M^2 (DLBCL) | Percentage of Participants With a Treatment Emergent Adverse Event (TEAE) (Safety Population) | % participants with Grade 5 TEAE | 2.5 Percentage of participants |
| INOTUZUMAB OZOGAMICIN MTD + RITUXIMAB 375 MG/M^2 (DLBCL) | Percentage of Participants With a Treatment Emergent Adverse Event (TEAE) (Safety Population) | % participants with Grade 3 or 4 TEAE | 75.0 Percentage of participants |
| INOTUZUMAB OZOGAMICIN MTD + RITUXIMAB 375 MG/M^2 (DLBCL) | Percentage of Participants With a Treatment Emergent Adverse Event (TEAE) (Safety Population) | % participants for study drug discontinuation | 50.0 Percentage of participants |
| INOTUZUMAB OZOGAMICIN MTD + RITUXIMAB 375 MG/M^2 (DLBCL) | Percentage of Participants With a Treatment Emergent Adverse Event (TEAE) (Safety Population) | % participants with dose reduction due to TEAE | 10.0 Percentage of participants |
| INOTUZUMAB OZOGAMICIN MTD + RITUXIMAB 375 MG/M^2 (DLBCL) | Percentage of Participants With a Treatment Emergent Adverse Event (TEAE) (Safety Population) | % participants with a TEAE | 100 Percentage of participants |
| INOTUZUMAB OZOGAMICIN MTD + RITUXIMAB 375 MG/M^2 (DLBCL) | Percentage of Participants With a Treatment Emergent Adverse Event (TEAE) (Safety Population) | % participants for study drug stopped temporarily | 40.0 Percentage of participants |
| INOTUZUMAB OZOGAMICIN MTD + RITUXIMAB 375 MG/M^2 (REFRACTORY) | Percentage of Participants With a Treatment Emergent Adverse Event (TEAE) (Safety Population) | % participants with a TEAE | 100 Percentage of participants |
| INOTUZUMAB OZOGAMICIN MTD + RITUXIMAB 375 MG/M^2 (REFRACTORY) | Percentage of Participants With a Treatment Emergent Adverse Event (TEAE) (Safety Population) | % participants with serious TEAE | 16.7 Percentage of participants |
| INOTUZUMAB OZOGAMICIN MTD + RITUXIMAB 375 MG/M^2 (REFRACTORY) | Percentage of Participants With a Treatment Emergent Adverse Event (TEAE) (Safety Population) | % participants for study drug stopped temporarily | 10.0 Percentage of participants |
| INOTUZUMAB OZOGAMICIN MTD + RITUXIMAB 375 MG/M^2 (REFRACTORY) | Percentage of Participants With a Treatment Emergent Adverse Event (TEAE) (Safety Population) | % participants for study drug discontinuation | 33.3 Percentage of participants |
| INOTUZUMAB OZOGAMICIN MTD + RITUXIMAB 375 MG/M^2 (REFRACTORY) | Percentage of Participants With a Treatment Emergent Adverse Event (TEAE) (Safety Population) | % participants with Grade 5 TEAE | 6.7 Percentage of participants |
| INOTUZUMAB OZOGAMICIN MTD + RITUXIMAB 375 MG/M^2 (REFRACTORY) | Percentage of Participants With a Treatment Emergent Adverse Event (TEAE) (Safety Population) | % participants with Grade 3 or 4 TEAE | 63.3 Percentage of participants |
| INOTUZUMAB OZOGAMICIN MTD + RITUXIMAB 375 MG/M^2 (REFRACTORY) | Percentage of Participants With a Treatment Emergent Adverse Event (TEAE) (Safety Population) | % participants with dose reduction due to TEAE | 0 Percentage of participants |
Secondary
Area Under the Serum Concentration-time Profile From Time Zero Extrapolated to Infinite Time (AUCinf) of Inotuzumab Ozogamicin Antibody in Participants Receiving Inotuzumab Ozogamicin MTD + Rituximab 375 mg/m2 on Dosing Day 30 and Day 58
AUCinf: AUClast+(Clast/kel) where Clast is the predicted serum concentration at the last quantifiable timepoint estimated from the log-linear regression analysis. Study Days Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57 and Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85 correspond to Dosing Day 30 for Cycle 2 and Dosing Day 58 for Cycle 3.
Time frame: Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57; Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85
Population: PK population
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| INOTUZUMAB OZOGAMICIN + RITUXIMAB 375 MG/M^2 | Area Under the Serum Concentration-time Profile From Time Zero Extrapolated to Infinite Time (AUCinf) of Inotuzumab Ozogamicin Antibody in Participants Receiving Inotuzumab Ozogamicin MTD + Rituximab 375 mg/m2 on Dosing Day 30 and Day 58 | Dosing Day 30 | 83270 ng·hr/mL | Geometric Coefficient of Variation 36 |
| INOTUZUMAB OZOGAMICIN + RITUXIMAB 375 MG/M^2 | Area Under the Serum Concentration-time Profile From Time Zero Extrapolated to Infinite Time (AUCinf) of Inotuzumab Ozogamicin Antibody in Participants Receiving Inotuzumab Ozogamicin MTD + Rituximab 375 mg/m2 on Dosing Day 30 and Day 58 | Dosing Day 58 | 93760 ng·hr/mL | Geometric Coefficient of Variation 30 |
Secondary
Area Under the Serum Concentration-time Profile From Time Zero Extrapolated to Infinite Time (AUCinf) of Inotuzumab Ozogamicin in Participants Receiving Inotuzumab Ozogamicin MTD + Rituximab 375 mg/m^2 on Dosing Day 30 and Day 58
Serum concentration of inotuzumab ozogamicin on Dosing Days 30 and 58 were measured. AUCinf of inotuzumab ozogamicin was reported. AUCinf: AUClast (area under the serum concentration-time profile for inotuzumab ozogamicin from time zero to the time of the last quantifiable concentration) +(Clast \[last quantifiable concentration\]/kel \[elimination rate constant\]) where Clast is the predicted serum concentration of inotuzumab ozogamicin at the last quantifiable timepoint estimated from the log-linear regression analysis. Study Days Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57 and Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85 correspond to Dosing Day 30 for Cycle 2 and Dosing Day 58 for Cycle 3.
Time frame: Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57; Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85
Population: PK population
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| INOTUZUMAB OZOGAMICIN + RITUXIMAB 375 MG/M^2 | Area Under the Serum Concentration-time Profile From Time Zero Extrapolated to Infinite Time (AUCinf) of Inotuzumab Ozogamicin in Participants Receiving Inotuzumab Ozogamicin MTD + Rituximab 375 mg/m^2 on Dosing Day 30 and Day 58 | Dosing Day 30 | 36030 ng.hr/mL | Geometric Coefficient of Variation 34 |
| INOTUZUMAB OZOGAMICIN + RITUXIMAB 375 MG/M^2 | Area Under the Serum Concentration-time Profile From Time Zero Extrapolated to Infinite Time (AUCinf) of Inotuzumab Ozogamicin in Participants Receiving Inotuzumab Ozogamicin MTD + Rituximab 375 mg/m^2 on Dosing Day 30 and Day 58 | Dosing Day 58 | 40550 ng.hr/mL | Geometric Coefficient of Variation 28 |
Secondary
Area Under the Steady-state Concentration-time Curve (AUClast) of Serum Inotuzumab Ozogamicin Antibody in Participants Receiving Inotuzumab Ozogamicin MTD + Rituximab 375 mg/m^2 on Dosing Day 1, Day 30 and Day 58
AUClast: AUC over dosage interval through last measurable time point, Tlast, using Linear/Log trapezoidal method. Study Days Cycle 1, Days 1 (0 hour), 2 (0, 1, 4 hours), 4, 8, 10, 15, and 29; Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57; and Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85 correspond to Dosing Day 1 for Cycle 1; Dosing Day 30 for Cycle 2; and Dosing Day 58 for Cycle 3.
Time frame: Cycle 1, Days 1 (0 hour), 2 (0, 1, 4 hours), 4, 8, 10, 15, and 29; Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57; Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85
Population: PK population
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| INOTUZUMAB OZOGAMICIN + RITUXIMAB 375 MG/M^2 | Area Under the Steady-state Concentration-time Curve (AUClast) of Serum Inotuzumab Ozogamicin Antibody in Participants Receiving Inotuzumab Ozogamicin MTD + Rituximab 375 mg/m^2 on Dosing Day 1, Day 30 and Day 58 | Dosing Day 1 | 25740 ng·hr/mL | Geometric Coefficient of Variation 139 |
| INOTUZUMAB OZOGAMICIN + RITUXIMAB 375 MG/M^2 | Area Under the Steady-state Concentration-time Curve (AUClast) of Serum Inotuzumab Ozogamicin Antibody in Participants Receiving Inotuzumab Ozogamicin MTD + Rituximab 375 mg/m^2 on Dosing Day 1, Day 30 and Day 58 | Dosing Day 30 | 61770 ng·hr/mL | Geometric Coefficient of Variation 88 |
| INOTUZUMAB OZOGAMICIN + RITUXIMAB 375 MG/M^2 | Area Under the Steady-state Concentration-time Curve (AUClast) of Serum Inotuzumab Ozogamicin Antibody in Participants Receiving Inotuzumab Ozogamicin MTD + Rituximab 375 mg/m^2 on Dosing Day 1, Day 30 and Day 58 | Dosing Day 58 | 72430 ng·hr/mL | Geometric Coefficient of Variation 95 |
Secondary
Area Under the Steady-state Serum Concentration-time Curve (AUClast) of Unconjugated Calicheamicin in Participants Receiving Inotuzumab Ozogamicin MTD + Rituximab 375 mg/m^2 on Dosing Day 1, Day 30 and Day 58
AUClast: AUC over dosage interval through last measurable time point, Tlast, using Linear/Log trapezoidal method. Study Days Cycle 1, Days 1 (0 hour), 2 (0, 1, 4 hours), 4, 8, 10, 15, and 29; Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57; and Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85 correspond to Dosing Day 1 for Cycle 1; Dosing Day 30 for Cycle 2; and Dosing Day 58 for Cycle 3.
Time frame: Cycle 1, Days 1 (0 hour), 2 (0, 1, 4 hours), 4, 8, 10, 15, and 29; Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57; Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85
Population: PK population
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| INOTUZUMAB OZOGAMICIN + RITUXIMAB 375 MG/M^2 | Area Under the Steady-state Serum Concentration-time Curve (AUClast) of Unconjugated Calicheamicin in Participants Receiving Inotuzumab Ozogamicin MTD + Rituximab 375 mg/m^2 on Dosing Day 1, Day 30 and Day 58 | Dosing Day 1 | 0.0009904 ng·hr/mL | Geometric Coefficient of Variation 22500000 |
| INOTUZUMAB OZOGAMICIN + RITUXIMAB 375 MG/M^2 | Area Under the Steady-state Serum Concentration-time Curve (AUClast) of Unconjugated Calicheamicin in Participants Receiving Inotuzumab Ozogamicin MTD + Rituximab 375 mg/m^2 on Dosing Day 1, Day 30 and Day 58 | Dosing Day 30 | 0.002008 ng·hr/mL | Geometric Coefficient of Variation 64300000 |
| INOTUZUMAB OZOGAMICIN + RITUXIMAB 375 MG/M^2 | Area Under the Steady-state Serum Concentration-time Curve (AUClast) of Unconjugated Calicheamicin in Participants Receiving Inotuzumab Ozogamicin MTD + Rituximab 375 mg/m^2 on Dosing Day 1, Day 30 and Day 58 | Dosing Day 58 | 0.005896 ng·hr/mL | Geometric Coefficient of Variation 1370000000 |
Secondary
Area Under the Steady-state Serum Concentration-time Curve (AUCtau) for Total Calicheamicin (Conjugated Plus Unconjugated) in Participants Receiving Inotuzumab Ozogamicin MTD + Rituximab 375 mg/m^2 on Dosing Day 1, Day 30, and Day 58
AUCtau=AUC over dosage interval tau calculated using Linear/log trapezoidal method. Study Days Cycle 1, Days 1 (0 hour), 2 (0, 1, 4 hours), 4, 8, 10, 15, and 29; Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57; and Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85 correspond to Dosing Day 1 for Cycle 1; Dosing Day 30 for Cycle 2; and Dosing Day 58 for Cycle 3.
Time frame: Cycle 1, Days 1 (0 hour), 2 (0, 1, 4 hours), 4, 8, 10, 15, and 29; Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57; Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85
Population: PK population
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| INOTUZUMAB OZOGAMICIN + RITUXIMAB 375 MG/M^2 | Area Under the Steady-state Serum Concentration-time Curve (AUCtau) for Total Calicheamicin (Conjugated Plus Unconjugated) in Participants Receiving Inotuzumab Ozogamicin MTD + Rituximab 375 mg/m^2 on Dosing Day 1, Day 30, and Day 58 | Dosing Day 1 | 3201 ng·hr/mL | Geometric Coefficient of Variation 78 |
| INOTUZUMAB OZOGAMICIN + RITUXIMAB 375 MG/M^2 | Area Under the Steady-state Serum Concentration-time Curve (AUCtau) for Total Calicheamicin (Conjugated Plus Unconjugated) in Participants Receiving Inotuzumab Ozogamicin MTD + Rituximab 375 mg/m^2 on Dosing Day 1, Day 30, and Day 58 | Dosing Day 30 | 7794 ng·hr/mL | Geometric Coefficient of Variation 38 |
| INOTUZUMAB OZOGAMICIN + RITUXIMAB 375 MG/M^2 | Area Under the Steady-state Serum Concentration-time Curve (AUCtau) for Total Calicheamicin (Conjugated Plus Unconjugated) in Participants Receiving Inotuzumab Ozogamicin MTD + Rituximab 375 mg/m^2 on Dosing Day 1, Day 30, and Day 58 | Dosing Day 58 | 9197 ng·hr/mL | Geometric Coefficient of Variation 54 |
Secondary
Area Under the Steady-state Serum Concentration-time Curve (AUCtau) of Inotuzumab Ozogamicin Antibody in Participants Receiving Inotuzumab Ozogamicin MTD+ Rituximab 375 mg/m^2 on Dosing Day 1, Day 30, and Day 58
AUCtau=AUC over dosage interval tau calculated using Linear/log trapezoidal method. Study Days Cycle 1, Days 1 (0 hour), 2 (0, 1, 4 hours), 4, 8, 10, 15, and 29; Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57; and Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85 correspond to Dosing Day 1 for Cycle 1; Dosing Day 30 for Cycle 2; and Dosing Day 58 for Cycle 3.
Time frame: Cycle 1, Days 1 (0 hour), 2 (0, 1, 4 hours), 4, 8, 10, 15, and 29; Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57; Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85
Population: PK population
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| INOTUZUMAB OZOGAMICIN + RITUXIMAB 375 MG/M^2 | Area Under the Steady-state Serum Concentration-time Curve (AUCtau) of Inotuzumab Ozogamicin Antibody in Participants Receiving Inotuzumab Ozogamicin MTD+ Rituximab 375 mg/m^2 on Dosing Day 1, Day 30, and Day 58 | Dosing Day 1 | 40180 ng·hr/mL | Geometric Coefficient of Variation 51 |
| INOTUZUMAB OZOGAMICIN + RITUXIMAB 375 MG/M^2 | Area Under the Steady-state Serum Concentration-time Curve (AUCtau) of Inotuzumab Ozogamicin Antibody in Participants Receiving Inotuzumab Ozogamicin MTD+ Rituximab 375 mg/m^2 on Dosing Day 1, Day 30, and Day 58 | Dosing Day 30 | 80060 ng·hr/mL | Geometric Coefficient of Variation 37 |
| INOTUZUMAB OZOGAMICIN + RITUXIMAB 375 MG/M^2 | Area Under the Steady-state Serum Concentration-time Curve (AUCtau) of Inotuzumab Ozogamicin Antibody in Participants Receiving Inotuzumab Ozogamicin MTD+ Rituximab 375 mg/m^2 on Dosing Day 1, Day 30, and Day 58 | Dosing Day 58 | 91370 ng·hr/mL | Geometric Coefficient of Variation 32 |
Secondary
Area Under the Steady-state Serum Concentration-time Curve (AUCtau) of Inotuzumab Ozogamicin in Participants Receving Inotuzumab Ozogamicin MTD + Rituximab 375 mg/m^2 on Dosing Day 1, Day 30 and Day 58
Steady-state serum concentrations of inotuzumab ozogamicin on Dosing Days 1, 30 and 58 were measured. AUCtau of inotuzumab ozogamicin was reported. AUCtau=AUC over dosage interval tau calculated using Linear/log trapezoidal method. Study Days Cycle 1, Days 1 (0 hour), 2 (0, 1, 4 hours), 4, 8, 10, 15, and 29; Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57; and Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85 correspond to Dosing Day 1 for Cycle 1; Dosing Day 30 for Cycle 2; and Dosing Day 58 for Cycle 3.
Time frame: Cycle 1, Days 1 (0 hour), 2 (0, 1, 4 hours), 4, 8, 10, 15, and 29; Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57; Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85
Population: PK population
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| INOTUZUMAB OZOGAMICIN + RITUXIMAB 375 MG/M^2 | Area Under the Steady-state Serum Concentration-time Curve (AUCtau) of Inotuzumab Ozogamicin in Participants Receving Inotuzumab Ozogamicin MTD + Rituximab 375 mg/m^2 on Dosing Day 1, Day 30 and Day 58 | Dosing Day 1 | 18660 ng.hr/mL | Geometric Coefficient of Variation 36 |
| INOTUZUMAB OZOGAMICIN + RITUXIMAB 375 MG/M^2 | Area Under the Steady-state Serum Concentration-time Curve (AUCtau) of Inotuzumab Ozogamicin in Participants Receving Inotuzumab Ozogamicin MTD + Rituximab 375 mg/m^2 on Dosing Day 1, Day 30 and Day 58 | Dosing Day 30 | 35900 ng.hr/mL | Geometric Coefficient of Variation 28 |
| INOTUZUMAB OZOGAMICIN + RITUXIMAB 375 MG/M^2 | Area Under the Steady-state Serum Concentration-time Curve (AUCtau) of Inotuzumab Ozogamicin in Participants Receving Inotuzumab Ozogamicin MTD + Rituximab 375 mg/m^2 on Dosing Day 1, Day 30 and Day 58 | Dosing Day 58 | 38820 ng.hr/mL | Geometric Coefficient of Variation 30 |
Secondary
AUCinf of Total Calicheamicin (Conjugated + Unconjugated) in Participants Receiving Inotuzumab Ozogamicin MTD + Rituximab 375 mg/m^2 on Dosing Day 30 and Day 58
AUCinf: AUClast+(Clast/kel) where Clast is the predicted serum concentration at the last quantifiable timepoint estimated from the log-linear regression analysis. Study Days Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57 and Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85 correspond to Dosing Day 30 for Cycle 2 and Dosing Day 58 for Cycle 3.
Time frame: Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57; Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85
Population: PK population
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| INOTUZUMAB OZOGAMICIN + RITUXIMAB 375 MG/M^2 | AUCinf of Total Calicheamicin (Conjugated + Unconjugated) in Participants Receiving Inotuzumab Ozogamicin MTD + Rituximab 375 mg/m^2 on Dosing Day 30 and Day 58 | Dosing Day 30 | 8437 ng·hr/mL | Geometric Coefficient of Variation 39 |
| INOTUZUMAB OZOGAMICIN + RITUXIMAB 375 MG/M^2 | AUCinf of Total Calicheamicin (Conjugated + Unconjugated) in Participants Receiving Inotuzumab Ozogamicin MTD + Rituximab 375 mg/m^2 on Dosing Day 30 and Day 58 | Dosing Day 58 | 10060 ng·hr/mL | Geometric Coefficient of Variation 58 |
Secondary
AUClast of Inotuzumab Ozogamicin in Participants Receiving Inotuzumab Ozogamicin MTD + Rituximab 375 mg/m^2 on Dosing Day 1, Day 30 and Day 58
Serum concentration of inotuzumab ozogamicin on Dosing Days 1, 30 and 58 were measured. AUC of inotuzumab ozogamicin was reported. AUClast is area under the serum concentration-time profile from time zero to the time of the Clast, using Linear/Log trapezoidal method. Study Days Cycle 1, Days 1 (0 hour), 2 (0, 1, 4 hours), 4, 8, 10, 15, and 29; Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57; and Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85 correspond to Dosing Day 1 for Cycle 1; Dosing Day 30 for Cycle 2; and Dosing Day 58 for Cycle 3.
Time frame: Cycle 1, Days 1 (0 hour), 2 (0, 1, 4 hours), 4, 8, 10, 15, and 29; Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57; Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85
Population: PK population: all participants dosed with inotuzumab ozogamicin.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| INOTUZUMAB OZOGAMICIN + RITUXIMAB 375 MG/M^2 | AUClast of Inotuzumab Ozogamicin in Participants Receiving Inotuzumab Ozogamicin MTD + Rituximab 375 mg/m^2 on Dosing Day 1, Day 30 and Day 58 | Dosing Day 1 | 6157 ng*h/mL | Geometric Coefficient of Variation 190 |
| INOTUZUMAB OZOGAMICIN + RITUXIMAB 375 MG/M^2 | AUClast of Inotuzumab Ozogamicin in Participants Receiving Inotuzumab Ozogamicin MTD + Rituximab 375 mg/m^2 on Dosing Day 1, Day 30 and Day 58 | Dosing Day 30 | 9664 ng*h/mL | Geometric Coefficient of Variation 76191 |
| INOTUZUMAB OZOGAMICIN + RITUXIMAB 375 MG/M^2 | AUClast of Inotuzumab Ozogamicin in Participants Receiving Inotuzumab Ozogamicin MTD + Rituximab 375 mg/m^2 on Dosing Day 1, Day 30 and Day 58 | Dosing Day 58 | 17320 ng*h/mL | Geometric Coefficient of Variation 225 |
Secondary
AUClast of Total Calicheamicin (Conjugated Plus Unconjugated) in Participants Receiving Inotuzumab Ozogamicin MTD + Rituximab 375 mg/m^2 on Dosing Day 1, Day 30 and Day 58
AUClast: AUC over dosage interval through last measurable time point, Tlast, using Linear/Log trapezoidal method. Study Days Cycle 1, Days 1 (0 hour), 2 (0, 1, 4 hours), 4, 8, 10, 15, and 29; Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57; and Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85 correspond to Dosing Day 1 for Cycle 1; Dosing Day 30 for Cycle 2; and Dosing Day 58 for Cycle 3.
Time frame: Cycle 1, Days 1 (0 hour), 2 (0, 1, 4 hours), 4, 8, 10, 15, and 29; Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57; Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85
Population: PK population
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| INOTUZUMAB OZOGAMICIN + RITUXIMAB 375 MG/M^2 | AUClast of Total Calicheamicin (Conjugated Plus Unconjugated) in Participants Receiving Inotuzumab Ozogamicin MTD + Rituximab 375 mg/m^2 on Dosing Day 1, Day 30 and Day 58 | Dosing Day 1 | 1901 n*hr/mL | Geometric Coefficient of Variation 192 |
| INOTUZUMAB OZOGAMICIN + RITUXIMAB 375 MG/M^2 | AUClast of Total Calicheamicin (Conjugated Plus Unconjugated) in Participants Receiving Inotuzumab Ozogamicin MTD + Rituximab 375 mg/m^2 on Dosing Day 1, Day 30 and Day 58 | Dosing Day 30 | 6129 n*hr/mL | Geometric Coefficient of Variation 85 |
| INOTUZUMAB OZOGAMICIN + RITUXIMAB 375 MG/M^2 | AUClast of Total Calicheamicin (Conjugated Plus Unconjugated) in Participants Receiving Inotuzumab Ozogamicin MTD + Rituximab 375 mg/m^2 on Dosing Day 1, Day 30 and Day 58 | Dosing Day 58 | 6755 n*hr/mL | Geometric Coefficient of Variation 145 |
Secondary
Average Serum Concentration at Steady State (Cav) of Inotuzumab Ozogamicin in Participants Receiving Inotuzumab Ozogamicin MTD + Rituximab 375 mg/m^2 on Dosing Day 30 and Day 58
Cav: AUCtau (Area under the concentration time profile)/tau for Dosing Day 30 Cycle 2 and Dosing Day 58 Cycle 3. Study Days Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57 and Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85 correspond to Dosing Day 30 for Cycle 2 and Dosing Day 58 for Cycle 3.
Time frame: Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57; Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85
Population: PK population
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| INOTUZUMAB OZOGAMICIN + RITUXIMAB 375 MG/M^2 | Average Serum Concentration at Steady State (Cav) of Inotuzumab Ozogamicin in Participants Receiving Inotuzumab Ozogamicin MTD + Rituximab 375 mg/m^2 on Dosing Day 30 and Day 58 | Dosing Day 30 | 53.43 ng/mL | Geometric Coefficient of Variation 28 |
| INOTUZUMAB OZOGAMICIN + RITUXIMAB 375 MG/M^2 | Average Serum Concentration at Steady State (Cav) of Inotuzumab Ozogamicin in Participants Receiving Inotuzumab Ozogamicin MTD + Rituximab 375 mg/m^2 on Dosing Day 30 and Day 58 | Dosing Day 58 | 57.77 ng/mL | Geometric Coefficient of Variation 30 |
Secondary
Average Serum Concentration (Cav) of Inotuzumab Ozogamicin Antibody in Participants Receiving Inotuzumab Ozogamicin MTD + Rituximab 375 mg/m^2 on Dosing Day 30 and Day 58
Cav: AUCtau/tau for Dosing Day 30 Cycle 2 and Dosing Day 58 Cycle 3. Study Days Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57 and Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85 correspond to Dosing Day 30 for Cycle 2 and Dosing Day 58 for Cycle 3.
Time frame: Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57; Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85
Population: PK population
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| INOTUZUMAB OZOGAMICIN + RITUXIMAB 375 MG/M^2 | Average Serum Concentration (Cav) of Inotuzumab Ozogamicin Antibody in Participants Receiving Inotuzumab Ozogamicin MTD + Rituximab 375 mg/m^2 on Dosing Day 30 and Day 58 | Dosing Day 30 | 119.2 ng/mL | Geometric Coefficient of Variation 37 |
| INOTUZUMAB OZOGAMICIN + RITUXIMAB 375 MG/M^2 | Average Serum Concentration (Cav) of Inotuzumab Ozogamicin Antibody in Participants Receiving Inotuzumab Ozogamicin MTD + Rituximab 375 mg/m^2 on Dosing Day 30 and Day 58 | Dosing Day 58 | 136 ng/mL | Geometric Coefficient of Variation 32 |
Secondary
Average Serum Concentration (Cav) of Total Calicheamicin (Conjugated Plus Unconjugated) in Participants Receiving Inotuzumab Ozogamicin MTD + Rituximab 375 mg/m^2 on Dosing Day 30 and Day 58
Cav: AUCtau/tau for Dosing Day 30 Cycle 2 and Dosing Day 58 Cycle 3. Study Days Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57 and Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85 correspond to Dosing Day 30 for Cycle 2 and Dosing Day 58 for Cycle 3.
Time frame: Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57; Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85
Population: PK population
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| INOTUZUMAB OZOGAMICIN + RITUXIMAB 375 MG/M^2 | Average Serum Concentration (Cav) of Total Calicheamicin (Conjugated Plus Unconjugated) in Participants Receiving Inotuzumab Ozogamicin MTD + Rituximab 375 mg/m^2 on Dosing Day 30 and Day 58 | Dosing Day 30 | 11.60 ng/mL | Geometric Coefficient of Variation 38 |
| INOTUZUMAB OZOGAMICIN + RITUXIMAB 375 MG/M^2 | Average Serum Concentration (Cav) of Total Calicheamicin (Conjugated Plus Unconjugated) in Participants Receiving Inotuzumab Ozogamicin MTD + Rituximab 375 mg/m^2 on Dosing Day 30 and Day 58 | Dosing Day 58 | 13.69 ng/mL | Geometric Coefficient of Variation 54 |
Secondary
Clearance (CL) of Serum Inotuzumab Ozogamicin Antibody in Participants Receiving Inotuzumab Ozogamicin MTD + Rituximab 375 mg/m^2 on Dosing Day 30 and Day 58
Clearance defined as Dose/AUCinf. Study Days Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57 and Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85 correspond to Dosing Day 30 for Cycle 2 and Dosing Day 58 for Cycle 3.
Time frame: Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57; Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85
Population: PK populatoin
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| INOTUZUMAB OZOGAMICIN + RITUXIMAB 375 MG/M^2 | Clearance (CL) of Serum Inotuzumab Ozogamicin Antibody in Participants Receiving Inotuzumab Ozogamicin MTD + Rituximab 375 mg/m^2 on Dosing Day 30 and Day 58 | Dosing Day 30 | 0.04240 L/hr | Geometric Coefficient of Variation 41 |
| INOTUZUMAB OZOGAMICIN + RITUXIMAB 375 MG/M^2 | Clearance (CL) of Serum Inotuzumab Ozogamicin Antibody in Participants Receiving Inotuzumab Ozogamicin MTD + Rituximab 375 mg/m^2 on Dosing Day 30 and Day 58 | Dosing Day 58 | 0.03699 L/hr | Geometric Coefficient of Variation 36 |
Secondary
Clearance (CL) of Serum Inotuzumab Ozogamicin in Participants Receiving Inotuzumab+Rituximab on Dosing Day 30 and Day 58
Clearance is defined as Dose/AUCinf. Study Days Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57 and Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85 correspond to Dosing Day 30 for Cycle 2 and Dosing Day 58 for Cycle 3.
Time frame: Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57; Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85
Population: PK population
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| INOTUZUMAB OZOGAMICIN + RITUXIMAB 375 MG/M^2 | Clearance (CL) of Serum Inotuzumab Ozogamicin in Participants Receiving Inotuzumab+Rituximab on Dosing Day 30 and Day 58 | Cycle 2 Day 30 | 0.09855 L/hr | Geometric Coefficient of Variation 33 |
| INOTUZUMAB OZOGAMICIN + RITUXIMAB 375 MG/M^2 | Clearance (CL) of Serum Inotuzumab Ozogamicin in Participants Receiving Inotuzumab+Rituximab on Dosing Day 30 and Day 58 | Cycle 3 Day 58 | 0.08743 L/hr | Geometric Coefficient of Variation 37 |
Secondary
Clearance (CL) of Total Calicheamicin (Conjugated Plus Unconjugated) in Participants Receiving Inotuzumab Ozogamicin MTD + Rituximab 375 mg/m^2 on Dosing Day 30 and Day 58
Clearance defined as Dose/AUCinf. Corresponds to Dosing Day 30 for Cycle 2 and dosing Day 58 for Cycle 3. Study Days Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57 and Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85 correspond to Dosing Day 30 for Cycle 2 and Dosing Day 58 for Cycle 3.
Time frame: Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57; Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85
Population: PK population
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| INOTUZUMAB OZOGAMICIN + RITUXIMAB 375 MG/M^2 | Clearance (CL) of Total Calicheamicin (Conjugated Plus Unconjugated) in Participants Receiving Inotuzumab Ozogamicin MTD + Rituximab 375 mg/m^2 on Dosing Day 30 and Day 58 | Dosing Day 30 | 0.4353 L/hr | Geometric Coefficient of Variation 40 |
| INOTUZUMAB OZOGAMICIN + RITUXIMAB 375 MG/M^2 | Clearance (CL) of Total Calicheamicin (Conjugated Plus Unconjugated) in Participants Receiving Inotuzumab Ozogamicin MTD + Rituximab 375 mg/m^2 on Dosing Day 30 and Day 58 | Dosing Day 58 | 0.3799 L/hr | Geometric Coefficient of Variation 57 |
Secondary
Duration of Response (CR+CRu+PR)
Time from date measurement criteria met for CR, CRu, or PR (whichever occurred first) until first date relapsed disease/date of death. CR: Complete disappearance of all detectable clinical, radiographic evidence of disease, disease-related symptoms, normalization of NHL assignable biochemical abnormalities; lymph nodes, nodal masses regressed to normal size; spleen size regressed, not palpable on physical exam, size of other organs enlarged due to disease. CRu: CR but allows for: residual lymph node mass \>1.5 cm in greatest transverse diameter that regressed \>75% in product diameter. Individual nodes previously confluent, regressed by \>75% in their product diameters; Indeterminate bone marrow. PR: ≥50% decrease in SPD of 6 largest dominant nodes/nodal masses; No increase in size of other nodes, liver, or spleen; Splenic/hepatic nodules regressed by ≥50% in SPD; Except splenic/hepatic nodules, involvement of other organs assessable and no measurable disease present.
Time frame: Time from date measurement criteria are met for CR, CRu, or PR (whichever status is recorded first) until the first date relapsed disease or date of death (whichever occurs first) is objectively documented.
Population: ITT population. Calculated using Kaplan-Meier method using the number of participants that responded.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| INOTUZUMAB OZOGAMICIN + RITUXIMAB 375 MG/M^2 | Duration of Response (CR+CRu+PR) | NA Month |
| INOTUZUMAB OZOGAMICIN 1.3 MG/M^2 + RITUXIMAB 375 MG/M^2 | Duration of Response (CR+CRu+PR) | NA Month |
| INOTUZUMAB OZOGAMICIN 1.8 MG/M^2 + RITUXIMAB 375 MG/M^2 | Duration of Response (CR+CRu+PR) | NA Month |
| INOTUZUMAB OZOGAMICIN MTD + RITUXIMAB 375 MG/M^2 (FOLLICULAR) | Duration of Response (CR+CRu+PR) | NA Month |
| INOTUZUMAB OZOGAMICIN MTD + RITUXIMAB 375 MG/M^2 (DLBCL) | Duration of Response (CR+CRu+PR) | 43.2 Month |
| INOTUZUMAB OZOGAMICIN MTD + RITUXIMAB 375 MG/M^2 (REFRACTORY) | Duration of Response (CR+CRu+PR) | 3.9 Month |
Secondary
Kaplan-Meier Estimates of Overall Survival (OS)
OS was defined as the time from randomization to death due to any cause, censoring at the date of last contact. The Kaplan-Meier method was used to determine OS. 95% 2-sided confidence interval were calculated using stratified Cox proportional hazard regression.
Time frame: From the first dose up to 5 years post last dose
Population: ITT population. Calculated using Kaplan-Meier method.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| INOTUZUMAB OZOGAMICIN + RITUXIMAB 375 MG/M^2 | Kaplan-Meier Estimates of Overall Survival (OS) | 7.4 Months |
| INOTUZUMAB OZOGAMICIN 1.3 MG/M^2 + RITUXIMAB 375 MG/M^2 | Kaplan-Meier Estimates of Overall Survival (OS) | NA Months |
| INOTUZUMAB OZOGAMICIN 1.8 MG/M^2 + RITUXIMAB 375 MG/M^2 | Kaplan-Meier Estimates of Overall Survival (OS) | 16.9 Months |
| INOTUZUMAB OZOGAMICIN MTD + RITUXIMAB 375 MG/M^2 (FOLLICULAR) | Kaplan-Meier Estimates of Overall Survival (OS) | NA Months |
| INOTUZUMAB OZOGAMICIN MTD + RITUXIMAB 375 MG/M^2 (DLBCL) | Kaplan-Meier Estimates of Overall Survival (OS) | 58.3 Months |
| INOTUZUMAB OZOGAMICIN MTD + RITUXIMAB 375 MG/M^2 (REFRACTORY) | Kaplan-Meier Estimates of Overall Survival (OS) | 8.4 Months |
Secondary
Kaplan-Meier Estimates of Progression Free Survival (PFS)
The Kaplan-Meier method was used to determine PFS. 95% 2-sided confidence interval were calculated using stratified Cox proportional hazard regression. Relapsed or Progressive Disease (PD) requires the following: a. Appearance of any new lesions, b. Increase by \>= 50% in the size of previously involved sites, c. \>= 50% increase in greatest diameter of any previously identified node greater than 1 cm in its short axis or in the SPD of more than one node, d. \>= 50% increase from nadir in the product diameter of any previously identified abnormal node for PRs or nonresponders, e. Enlarging spleen or liver.
Time frame: From the date of first dose of test article until the first date on which disease progression or death was documented or new anticancer start, any of which could be reported up to 5 years post last dose
Population: ITT population. Calculated using Kaplan-Meier method.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| INOTUZUMAB OZOGAMICIN + RITUXIMAB 375 MG/M^2 | Kaplan-Meier Estimates of Progression Free Survival (PFS) | 1.7 Months |
| INOTUZUMAB OZOGAMICIN 1.3 MG/M^2 + RITUXIMAB 375 MG/M^2 | Kaplan-Meier Estimates of Progression Free Survival (PFS) | NA Months |
| INOTUZUMAB OZOGAMICIN 1.8 MG/M^2 + RITUXIMAB 375 MG/M^2 | Kaplan-Meier Estimates of Progression Free Survival (PFS) | NA Months |
| INOTUZUMAB OZOGAMICIN MTD + RITUXIMAB 375 MG/M^2 (FOLLICULAR) | Kaplan-Meier Estimates of Progression Free Survival (PFS) | NA Months |
| INOTUZUMAB OZOGAMICIN MTD + RITUXIMAB 375 MG/M^2 (DLBCL) | Kaplan-Meier Estimates of Progression Free Survival (PFS) | 17.1 Months |
| INOTUZUMAB OZOGAMICIN MTD + RITUXIMAB 375 MG/M^2 (REFRACTORY) | Kaplan-Meier Estimates of Progression Free Survival (PFS) | 1.8 Months |
Secondary
Kaplan-Meier Estimates of the Probability of Being Event Free at 6 Months
Time-to-Tumor Progression (TTP): is defined as the interval from the first dose of the test article until the first date on which relapsed disease or progression, or death secondary to progression is documented, censored at the last disease assessment. Relapsed or Progressive Disease (PD) requires the following: a. Appearance of any new lesions, b. Increase by \>=50% in the size of previously involved sites, c. \>= 50% increase in greatest diameter of any previously identified node greater than 1 cm in its short axis or in the SPD of more than one node, d. \>= 50% increase from nadir in the product diameter of any previously identified abnormal node for PRs or nonresponders, e. Enlarging spleen or liver. The Kaplan-Meier method was used to determineTTP. 95% 2-sided confidence interval were calculated using stratified Cox proportional hazard regression.
Time frame: From enrollment to up to 6 months from 1st dose.
Population: ITT population. Calculated using Kaplan-Meier method.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| INOTUZUMAB OZOGAMICIN + RITUXIMAB 375 MG/M^2 | Kaplan-Meier Estimates of the Probability of Being Event Free at 6 Months | 0.4 Probability |
| INOTUZUMAB OZOGAMICIN 1.3 MG/M^2 + RITUXIMAB 375 MG/M^2 | Kaplan-Meier Estimates of the Probability of Being Event Free at 6 Months | 1.0 Probability |
| INOTUZUMAB OZOGAMICIN 1.8 MG/M^2 + RITUXIMAB 375 MG/M^2 | Kaplan-Meier Estimates of the Probability of Being Event Free at 6 Months | 0.7 Probability |
| INOTUZUMAB OZOGAMICIN MTD + RITUXIMAB 375 MG/M^2 (FOLLICULAR) | Kaplan-Meier Estimates of the Probability of Being Event Free at 6 Months | 1.0 Probability |
| INOTUZUMAB OZOGAMICIN MTD + RITUXIMAB 375 MG/M^2 (DLBCL) | Kaplan-Meier Estimates of the Probability of Being Event Free at 6 Months | 0.7 Probability |
| INOTUZUMAB OZOGAMICIN MTD + RITUXIMAB 375 MG/M^2 (REFRACTORY) | Kaplan-Meier Estimates of the Probability of Being Event Free at 6 Months | 0.3 Probability |
Secondary
Kaplan-Meier Estimates of the Probability of Being Progression Free at 6 Months
Progression Free Survival is defined as the time interval from the first dose of test article until the first date on which relapsed disease, progression, initiation of new anti-cancer treatment due to persistent/refractory disease, or death was documented, censored at the last tumor evaluation.
Time frame: From the first dose to 6 months after first dose
Population: ITT population; Calculated using Kaplan-Meier method.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| INOTUZUMAB OZOGAMICIN + RITUXIMAB 375 MG/M^2 | Kaplan-Meier Estimates of the Probability of Being Progression Free at 6 Months | 0.4 Probability |
| INOTUZUMAB OZOGAMICIN 1.3 MG/M^2 + RITUXIMAB 375 MG/M^2 | Kaplan-Meier Estimates of the Probability of Being Progression Free at 6 Months | 1.0 Probability |
| INOTUZUMAB OZOGAMICIN 1.8 MG/M^2 + RITUXIMAB 375 MG/M^2 | Kaplan-Meier Estimates of the Probability of Being Progression Free at 6 Months | 0.6 Probability |
| INOTUZUMAB OZOGAMICIN MTD + RITUXIMAB 375 MG/M^2 (FOLLICULAR) | Kaplan-Meier Estimates of the Probability of Being Progression Free at 6 Months | 1.0 Probability |
| INOTUZUMAB OZOGAMICIN MTD + RITUXIMAB 375 MG/M^2 (DLBCL) | Kaplan-Meier Estimates of the Probability of Being Progression Free at 6 Months | 0.7 Probability |
| INOTUZUMAB OZOGAMICIN MTD + RITUXIMAB 375 MG/M^2 (REFRACTORY) | Kaplan-Meier Estimates of the Probability of Being Progression Free at 6 Months | 0.2 Probability |
Secondary
Kaplan-Meier Estimates of the Probability of Survival at 6 Months
Overall Survival (OS) was defined as the time from randomization to death due to any cause, censoring at the date of last contact. The Kaplan-Meier method was used to determine OS. 95% 2-sided confidence interval were calculated using stratified Cox proportional hazard regression.
Time frame: From the first dose to 6 months after first dose.
Population: ITT population. Calculated using Kaplan-Meier method.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| INOTUZUMAB OZOGAMICIN + RITUXIMAB 375 MG/M^2 | Kaplan-Meier Estimates of the Probability of Survival at 6 Months | 0.6 Probability |
| INOTUZUMAB OZOGAMICIN 1.3 MG/M^2 + RITUXIMAB 375 MG/M^2 | Kaplan-Meier Estimates of the Probability of Survival at 6 Months | 1.0 Probability |
| INOTUZUMAB OZOGAMICIN 1.8 MG/M^2 + RITUXIMAB 375 MG/M^2 | Kaplan-Meier Estimates of the Probability of Survival at 6 Months | 0.7 Probability |
| INOTUZUMAB OZOGAMICIN MTD + RITUXIMAB 375 MG/M^2 (FOLLICULAR) | Kaplan-Meier Estimates of the Probability of Survival at 6 Months | 1.0 Probability |
| INOTUZUMAB OZOGAMICIN MTD + RITUXIMAB 375 MG/M^2 (DLBCL) | Kaplan-Meier Estimates of the Probability of Survival at 6 Months | 0.9 Probability |
| INOTUZUMAB OZOGAMICIN MTD + RITUXIMAB 375 MG/M^2 (REFRACTORY) | Kaplan-Meier Estimates of the Probability of Survival at 6 Months | 0.6 Probability |
Secondary
Kaplan-Meier Estimates of Time to Tumor Progression (TTP)
TTP is defined as the interval from the first dose of the test article until the first date on which relapsed disease or progression, or death secondary to progression is documented, censored at the last disease assessment. Relapsed or Progressive Disease (PD) requires the following: a. Appearance of any new lesions, b. Increase by \>= 50% in the size of previously involved sites, c. \>= 50% increase in greatest diameter of any previously identified node greater than 1 cm in its short axis or in the SPD of more than one node, d. \>= 50% increase from nadir in the product diameter of any previously identified abnormal node for PRs or nonresponders, e. Enlarging spleen or liver. The Kaplan-Meier method was used to determine TTP. 95% 2-sided confidence interval were calculated using stratified Cox proportional hazard regression.
Time frame: From the date of first dose of test article until the first date on which disease progression or death was documented, any of which could be reported up to 5 years post last dose.
Population: ITT population. Calculated using Kaplan-Meier method.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| INOTUZUMAB OZOGAMICIN + RITUXIMAB 375 MG/M^2 | Kaplan-Meier Estimates of Time to Tumor Progression (TTP) | 1.7 Months |
| INOTUZUMAB OZOGAMICIN 1.3 MG/M^2 + RITUXIMAB 375 MG/M^2 | Kaplan-Meier Estimates of Time to Tumor Progression (TTP) | NA Months |
| INOTUZUMAB OZOGAMICIN 1.8 MG/M^2 + RITUXIMAB 375 MG/M^2 | Kaplan-Meier Estimates of Time to Tumor Progression (TTP) | NA Months |
| INOTUZUMAB OZOGAMICIN MTD + RITUXIMAB 375 MG/M^2 (FOLLICULAR) | Kaplan-Meier Estimates of Time to Tumor Progression (TTP) | NA Months |
| INOTUZUMAB OZOGAMICIN MTD + RITUXIMAB 375 MG/M^2 (DLBCL) | Kaplan-Meier Estimates of Time to Tumor Progression (TTP) | 45.1 Months |
| INOTUZUMAB OZOGAMICIN MTD + RITUXIMAB 375 MG/M^2 (REFRACTORY) | Kaplan-Meier Estimates of Time to Tumor Progression (TTP) | 1.7 Months |
Secondary
Mean Residence Time (MRT) of Total Calicheamicin (Conjugated Plus Unconjugated) in Participants Receiving Inotuzumab Ozogamicin MTD + Rituximab 375 mg/m^2 on Dosing Day 30 and Day 58
MRT: AUMCinf/AUCinf - DOF/2, where AUMCinf is the area under the first moment curve derived using the linear/log trapezoidal method, and DOF is the duration of the IV infusion dose. Study Days Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57 and Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85 correspond to Dosing Day 30 for Cycle 2 and Dosing Day 58 for Cycle 3.
Time frame: Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57; Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85
Population: PK population
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| INOTUZUMAB OZOGAMICIN + RITUXIMAB 375 MG/M^2 | Mean Residence Time (MRT) of Total Calicheamicin (Conjugated Plus Unconjugated) in Participants Receiving Inotuzumab Ozogamicin MTD + Rituximab 375 mg/m^2 on Dosing Day 30 and Day 58 | Dosing Day 30 | 167.5 hr | Geometric Coefficient of Variation 41 |
| INOTUZUMAB OZOGAMICIN + RITUXIMAB 375 MG/M^2 | Mean Residence Time (MRT) of Total Calicheamicin (Conjugated Plus Unconjugated) in Participants Receiving Inotuzumab Ozogamicin MTD + Rituximab 375 mg/m^2 on Dosing Day 30 and Day 58 | Dosing Day 58 | 199.5 hr | Geometric Coefficient of Variation 49 |
Secondary
Minimum Observed Serum Trough Concentration (Cmin) of Inotuzumab Ozogamicin Antibody in Participants Receiving Inotuzumab MTD + Rituximab 375 mg/m^2 on Dosing Day 30 and Day 58
Cmin: Lowest concentration observed during the dosing interval tau. Study Days Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57 and Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85 correspond to Dosing Day 30 for Cycle 2 and Dosing Day 58 for Cycle 3.
Time frame: Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57; Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85
Population: PK population
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| INOTUZUMAB OZOGAMICIN + RITUXIMAB 375 MG/M^2 | Minimum Observed Serum Trough Concentration (Cmin) of Inotuzumab Ozogamicin Antibody in Participants Receiving Inotuzumab MTD + Rituximab 375 mg/m^2 on Dosing Day 30 and Day 58 | Dosing Day 30 | 0.0001190 ng/mL | Geometric Coefficient of Variation 366 |
| INOTUZUMAB OZOGAMICIN + RITUXIMAB 375 MG/M^2 | Minimum Observed Serum Trough Concentration (Cmin) of Inotuzumab Ozogamicin Antibody in Participants Receiving Inotuzumab MTD + Rituximab 375 mg/m^2 on Dosing Day 30 and Day 58 | Dosing Day 58 | 0 ng/mL | Geometric Coefficient of Variation 0 |
Secondary
Minimum Observed Serum Trough Concentration (Cmin) of Inotuzumab Ozogamicin in Participants Receiving Inotuzumab+Rituximab on Dosing Day 30 and Day 58
Cmin: Lowest concentration observed during the dosing interval tau. Observed directly from data from Dosing Day 30 for Cycle 2; and Dosing Day 58 for Cycle 3. Study Days Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57 and Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85 correspond to Dosing Day 30 for Cycle 2 and Dosing Day 58 for Cycle 3.
Time frame: Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57; Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85
Population: PK population
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| INOTUZUMAB OZOGAMICIN + RITUXIMAB 375 MG/M^2 | Minimum Observed Serum Trough Concentration (Cmin) of Inotuzumab Ozogamicin in Participants Receiving Inotuzumab+Rituximab on Dosing Day 30 and Day 58 | Dosing Day 30 | 0.0001196 ng/mL | Geometric Coefficient of Variation 384 |
| INOTUZUMAB OZOGAMICIN + RITUXIMAB 375 MG/M^2 | Minimum Observed Serum Trough Concentration (Cmin) of Inotuzumab Ozogamicin in Participants Receiving Inotuzumab+Rituximab on Dosing Day 30 and Day 58 | Dosing Day 58 | 0 ng/mL | Geometric Coefficient of Variation 0 |
Secondary
Minimum Observed Serum Trough Concentration (Cmin) of Total Calicheamicin (Conjugated Plus Unconjugated) in Participants Receiving Inotuzumab Ozogamicin MTD + Rituximab 375 mg/m^2 on Dosing Day 30 and Day 58
Cmin: Lowest concentration observed during the dosing interval tau. Observed directly from data from Day 30 for Cycle 2; and Day 58 for Cycle 3. Study Days Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57 and Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85 correspond to Dosing Day 30 for Cycle 2 and Dosing Day 58 for Cycle 3.
Time frame: Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57; Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85
Population: PK population
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| INOTUZUMAB OZOGAMICIN + RITUXIMAB 375 MG/M^2 | Minimum Observed Serum Trough Concentration (Cmin) of Total Calicheamicin (Conjugated Plus Unconjugated) in Participants Receiving Inotuzumab Ozogamicin MTD + Rituximab 375 mg/m^2 on Dosing Day 30 and Day 58 | Dosing Day 30 | 0.0001326 ng/mL | Geometric Coefficient of Variation 564 |
| INOTUZUMAB OZOGAMICIN + RITUXIMAB 375 MG/M^2 | Minimum Observed Serum Trough Concentration (Cmin) of Total Calicheamicin (Conjugated Plus Unconjugated) in Participants Receiving Inotuzumab Ozogamicin MTD + Rituximab 375 mg/m^2 on Dosing Day 30 and Day 58 | Dosing Day 58 | 0.0001350 ng/mL | Geometric Coefficient of Variation 497 |
Secondary
Minimum Observed Serum Trough Concentration (Cmin) of Unconjugated Calicheamicin in Participants Receiving Inotuzumab Ozogamicin+Rituximab on Dosing Day 30 and Day 58
Cmin: Lowest concentration observed during the dosing interval tau. Study Days Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57 and Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85 correspond to Dosing Day 30 for Cycle 2 and Dosing Day 58 for Cycle 3.
Time frame: Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57; Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85
Population: PK population
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| INOTUZUMAB OZOGAMICIN + RITUXIMAB 375 MG/M^2 | Minimum Observed Serum Trough Concentration (Cmin) of Unconjugated Calicheamicin in Participants Receiving Inotuzumab Ozogamicin+Rituximab on Dosing Day 30 and Day 58 | Dosing Day 30 | 0.0001588 ng/mL | Geometric Coefficient of Variation 1044 |
| INOTUZUMAB OZOGAMICIN + RITUXIMAB 375 MG/M^2 | Minimum Observed Serum Trough Concentration (Cmin) of Unconjugated Calicheamicin in Participants Receiving Inotuzumab Ozogamicin+Rituximab on Dosing Day 30 and Day 58 | Dosing Day 58 | 0.0001495 ng/mL | Geometric Coefficient of Variation 811 |
Secondary
MRT of Inotuzumab Ozogamicin in Serum in Participants Receiving Inotuzumab Ozogamicin MTD + Rituximab 375 mg/m^2 on Dosing Day 30 and Day 58
MRT: AUMCinf/AUCinf - DOF (degrees of freedom)/2, where AUMCinf is the area under the first moment curve derived using the linear/log trapezoidal method, and DOF is the duration of the IV infusion dose. Study Days Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57 and Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85 correspond to Dosing Day 30 for Cycle 2 and Dosing Day 58 for Cycle 3.
Time frame: Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57; Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85
Population: PK population
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| INOTUZUMAB OZOGAMICIN + RITUXIMAB 375 MG/M^2 | MRT of Inotuzumab Ozogamicin in Serum in Participants Receiving Inotuzumab Ozogamicin MTD + Rituximab 375 mg/m^2 on Dosing Day 30 and Day 58 | Dosing Day 30 | 49.31 hr | Geometric Coefficient of Variation 39 |
| INOTUZUMAB OZOGAMICIN + RITUXIMAB 375 MG/M^2 | MRT of Inotuzumab Ozogamicin in Serum in Participants Receiving Inotuzumab Ozogamicin MTD + Rituximab 375 mg/m^2 on Dosing Day 30 and Day 58 | Dosing Day 58 | 59.24 hr | Geometric Coefficient of Variation 27 |
Secondary
Peak Concentration (Cmax) of Serum Inotuzumab Ozogamicin Antibody in Participants Receiving Inotuzumab Ozogamicin MTD + Rituximab 375 mg/m^2 on Dosing Day 1, Day 30 and Day 58
Cmax: Observed directly from data Study Days Cycle 1, Days 1 (0 hour), 2 (0, 1, 4 hours), 4, 8, 10, 15, and 29; Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57; and Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85 correspond to Dosing Day 1 for Cycle 1; Dosing Day 30 for Cycle 2; and Dosing Day 58 for Cycle 3.
Time frame: Cycle 1, Days 1 (0 hour), 2 (0, 1, 4 hours), 4, 8, 10, 15, and 29; Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57; Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85
Population: PK population
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| INOTUZUMAB OZOGAMICIN + RITUXIMAB 375 MG/M^2 | Peak Concentration (Cmax) of Serum Inotuzumab Ozogamicin Antibody in Participants Receiving Inotuzumab Ozogamicin MTD + Rituximab 375 mg/m^2 on Dosing Day 1, Day 30 and Day 58 | Dosing Day 1 | 776.6 ng/mL | Geometric Coefficient of Variation 36 |
| INOTUZUMAB OZOGAMICIN + RITUXIMAB 375 MG/M^2 | Peak Concentration (Cmax) of Serum Inotuzumab Ozogamicin Antibody in Participants Receiving Inotuzumab Ozogamicin MTD + Rituximab 375 mg/m^2 on Dosing Day 1, Day 30 and Day 58 | Dosing Day 30 | 700.4 ng/mL | Geometric Coefficient of Variation 448 |
| INOTUZUMAB OZOGAMICIN + RITUXIMAB 375 MG/M^2 | Peak Concentration (Cmax) of Serum Inotuzumab Ozogamicin Antibody in Participants Receiving Inotuzumab Ozogamicin MTD + Rituximab 375 mg/m^2 on Dosing Day 1, Day 30 and Day 58 | Dosing Day 58 | 653.0 ng/mL | Geometric Coefficient of Variation 625 |
Secondary
Peak Serum Concentration (Cmax) of Inotuzumab Ozogamicin in Participants Receving Inotuzumab Ozogamicin MTD + Rituximab 375 mg/m^2 on Dosing Day 1, Day 30 and Day 58
Serum concentration of inotuzumab ozogamicin on Dosing Days 1, 30, and 58 were measured. Cmax of inotuzumab ozogamicin was reported. Cmax was observed directly from data. Study Days Cycle 1, Days 1 (0 hour), 2 (0, 1, 4 hours), 4, 8, 10, 15, and 29; Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57; and Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85 correspond to Dosing Day 1 for Cycle 1; Dosing Day 30 for Cycle 2; and Dosing Day 58 for Cycle 3.
Time frame: Cycle 1, Days 1 (0 hour), 2 (0, 1, 4 hours), 4, 8, 10, 15, and 29; Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57; Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85
Population: PK population
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| INOTUZUMAB OZOGAMICIN + RITUXIMAB 375 MG/M^2 | Peak Serum Concentration (Cmax) of Inotuzumab Ozogamicin in Participants Receving Inotuzumab Ozogamicin MTD + Rituximab 375 mg/m^2 on Dosing Day 1, Day 30 and Day 58 | Dosing Day 1 | 600.2 ng/mL | Geometric Coefficient of Variation 42 |
| INOTUZUMAB OZOGAMICIN + RITUXIMAB 375 MG/M^2 | Peak Serum Concentration (Cmax) of Inotuzumab Ozogamicin in Participants Receving Inotuzumab Ozogamicin MTD + Rituximab 375 mg/m^2 on Dosing Day 1, Day 30 and Day 58 | Dosing Day 30 | 378.3 ng/mL | Geometric Coefficient of Variation 6435 |
| INOTUZUMAB OZOGAMICIN + RITUXIMAB 375 MG/M^2 | Peak Serum Concentration (Cmax) of Inotuzumab Ozogamicin in Participants Receving Inotuzumab Ozogamicin MTD + Rituximab 375 mg/m^2 on Dosing Day 1, Day 30 and Day 58 | Dosing Day 58 | 519.2 ng/mL | Geometric Coefficient of Variation 586 |
Secondary
Peak Serum Concentration (Cmax) of Total Calicheamicin (Conjugated Plus Unconjugated) in Participants Receiving Inotuzumab Ozogamicin MTD + Rituximab 375 mg/m^2 on Dosing Day 1, Day 30 and Day 58
Cmax: Observed directly from data Study Days Cycle 1, Days 1 (0 hour), 2 (0, 1, 4 hours), 4, 8, 10, 15, and 29; Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57; and Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85 correspond to Dosing Day 1 for Cycle 1; Dosing Day 30 for Cycle 2; and Dosing Day 58 for Cycle 3.
Time frame: Cycle 1, Days 1 (0 hour), 2 (0, 1, 4 hours), 4, 8, 10, 15, and 29; Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57; Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85
Population: PK population
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| INOTUZUMAB OZOGAMICIN + RITUXIMAB 375 MG/M^2 | Peak Serum Concentration (Cmax) of Total Calicheamicin (Conjugated Plus Unconjugated) in Participants Receiving Inotuzumab Ozogamicin MTD + Rituximab 375 mg/m^2 on Dosing Day 1, Day 30 and Day 58 | Dosing Day 1 | 54.36 ng/mL | Geometric Coefficient of Variation 226 |
| INOTUZUMAB OZOGAMICIN + RITUXIMAB 375 MG/M^2 | Peak Serum Concentration (Cmax) of Total Calicheamicin (Conjugated Plus Unconjugated) in Participants Receiving Inotuzumab Ozogamicin MTD + Rituximab 375 mg/m^2 on Dosing Day 1, Day 30 and Day 58 | Dosing Day 30 | 58.67 ng/mL | Geometric Coefficient of Variation 283 |
| INOTUZUMAB OZOGAMICIN + RITUXIMAB 375 MG/M^2 | Peak Serum Concentration (Cmax) of Total Calicheamicin (Conjugated Plus Unconjugated) in Participants Receiving Inotuzumab Ozogamicin MTD + Rituximab 375 mg/m^2 on Dosing Day 1, Day 30 and Day 58 | Dosing Day 58 | 64.43 ng/mL | Geometric Coefficient of Variation 47 |
Secondary
Peak Serum Concentration (Cmax) of Unconjugated Calicheamicin in Participants Receiving Inotuzumab Ozogamicin MTD + Rituximab 375 mg/m^2 on Dosing Day 1, Day 30 and Day 58
Cmax: Observed directly from data Study Days Cycle 1, Days 1 (0 hour), 2 (0, 1, 4 hours), 4, 8, 10, 15, and 29; Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57; and Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85 correspond to Dosing Day 1 for Cycle 1; Dosing Day 30 for Cycle 2; and Dosing Day 58 for Cycle 3.
Time frame: Cycle 1, Days 1 (0 hour), 2 (0, 1, 4 hours), 4, 8, 10, 15, and 29; Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57; Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85
Population: PK population
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| INOTUZUMAB OZOGAMICIN + RITUXIMAB 375 MG/M^2 | Peak Serum Concentration (Cmax) of Unconjugated Calicheamicin in Participants Receiving Inotuzumab Ozogamicin MTD + Rituximab 375 mg/m^2 on Dosing Day 1, Day 30 and Day 58 | Dosing Day 58 | 0.003250 ng/mL | Geometric Coefficient of Variation 6780000 |
| INOTUZUMAB OZOGAMICIN + RITUXIMAB 375 MG/M^2 | Peak Serum Concentration (Cmax) of Unconjugated Calicheamicin in Participants Receiving Inotuzumab Ozogamicin MTD + Rituximab 375 mg/m^2 on Dosing Day 1, Day 30 and Day 58 | Dosing Day 1 | 0.0005608 ng/mL | Geometric Coefficient of Variation 121496 |
| INOTUZUMAB OZOGAMICIN + RITUXIMAB 375 MG/M^2 | Peak Serum Concentration (Cmax) of Unconjugated Calicheamicin in Participants Receiving Inotuzumab Ozogamicin MTD + Rituximab 375 mg/m^2 on Dosing Day 1, Day 30 and Day 58 | Dosing Day 30 | 0.001153 ng/mL | Geometric Coefficient of Variation 1020000 |
Secondary
Percentage of Participants With Complete Response (CR), Unconfirmed CR (CRu), or Partial Response (PR)
CR: a. Complete disappearance of all detectable clinical and radiographic evidence of disease, disease-related symptoms, and normalization of NHL assignable biochemical abnormalities ; b. lymph nodes and nodal masses must have regressed to normal size; c. Spleen regressed in size and not palpable on physical exam, size of other organs enlarged due to disease decreased in size; d. Repeat bone marrow infiltrate clear. CRu: CR but allows for a. Residual lymph node mass \>1.5 cm in greatest transverse diameter has regressed by more than 75% in diameter. Individual nodes that were previously confluent regressed more than 75 % in their product diameters; b. Indeterminate bone marrow. PR: a. ≥50 % decrease in product of the diameters (SPD) of the 6 largest dominant nodes or nodal masses; b. No increase in size of other nodes, liver, or spleen, c. Liver or spleen nodules regressed ≥50% in the SPD; d. Other organs usually assessable, no measurable disease present.
Time frame: Approximately every 2 (during treatment) or 3 (during follow-up) to 6 months for up to 5 years from 1st dose
Population: ITT population: all participants enrolled into the intended dose scheme. Using exact method based on binomial distribution.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| INOTUZUMAB OZOGAMICIN + RITUXIMAB 375 MG/M^2 | Percentage of Participants With Complete Response (CR), Unconfirmed CR (CRu), or Partial Response (PR) | 40 Percentage of participants |
| INOTUZUMAB OZOGAMICIN 1.3 MG/M^2 + RITUXIMAB 375 MG/M^2 | Percentage of Participants With Complete Response (CR), Unconfirmed CR (CRu), or Partial Response (PR) | 100 Percentage of participants |
| INOTUZUMAB OZOGAMICIN 1.8 MG/M^2 + RITUXIMAB 375 MG/M^2 | Percentage of Participants With Complete Response (CR), Unconfirmed CR (CRu), or Partial Response (PR) | 57.1 Percentage of participants |
| INOTUZUMAB OZOGAMICIN MTD + RITUXIMAB 375 MG/M^2 (FOLLICULAR) | Percentage of Participants With Complete Response (CR), Unconfirmed CR (CRu), or Partial Response (PR) | 94.1 Percentage of participants |
| INOTUZUMAB OZOGAMICIN MTD + RITUXIMAB 375 MG/M^2 (DLBCL) | Percentage of Participants With Complete Response (CR), Unconfirmed CR (CRu), or Partial Response (PR) | 72.5 Percentage of participants |
| INOTUZUMAB OZOGAMICIN MTD + RITUXIMAB 375 MG/M^2 (REFRACTORY) | Percentage of Participants With Complete Response (CR), Unconfirmed CR (CRu), or Partial Response (PR) | 20 Percentage of participants |
Secondary
Serum Decay Half-Life (t1/2) of Inotuzumab Ozogamicin Antibody in Participants Receiving Inotuzumab Ozogamicin MTD + Rituximab on Dosing Day 30 and Day 58
Termnial half-life (t½): Loge(2)/kel, where kel is the terminal phase rate constant calculated by a linear regression of the log-linear concentration-time curve. Study Days Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57 and Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85 correspond to Dosing Day 30 for Cycle 2 and Dosing Day 58 for Cycle 3.
Time frame: Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57; Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85
Population: PK population
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| INOTUZUMAB OZOGAMICIN + RITUXIMAB 375 MG/M^2 | Serum Decay Half-Life (t1/2) of Inotuzumab Ozogamicin Antibody in Participants Receiving Inotuzumab Ozogamicin MTD + Rituximab on Dosing Day 30 and Day 58 | Dosing Day 30 | 99.35 hr |
| INOTUZUMAB OZOGAMICIN + RITUXIMAB 375 MG/M^2 | Serum Decay Half-Life (t1/2) of Inotuzumab Ozogamicin Antibody in Participants Receiving Inotuzumab Ozogamicin MTD + Rituximab on Dosing Day 30 and Day 58 | Dosing Day 58 | 103.5 hr |
Secondary
Serum Decay Half-Life (t1/2) of Inotuzumab Ozogamicin in Participants Receiving Inotuzumab Ozogamicin MTD + Rituximab 375 mg/m^2 on Dosing Day 30 and Day 58
Termnial half-life (t½): Loge(2)/kel, where kel is the terminal phase rate constant calculated by a linear regression of the log-linear concentration-time curve. Study Days Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57 and Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85 correspond to Dosing Day 30 for Cycle 2 and Dosing Day 58 for Cycle 3.
Time frame: Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57; Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85
Population: PK population
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| INOTUZUMAB OZOGAMICIN + RITUXIMAB 375 MG/M^2 | Serum Decay Half-Life (t1/2) of Inotuzumab Ozogamicin in Participants Receiving Inotuzumab Ozogamicin MTD + Rituximab 375 mg/m^2 on Dosing Day 30 and Day 58 | Dosing Day 30 | 40.15 hr |
| INOTUZUMAB OZOGAMICIN + RITUXIMAB 375 MG/M^2 | Serum Decay Half-Life (t1/2) of Inotuzumab Ozogamicin in Participants Receiving Inotuzumab Ozogamicin MTD + Rituximab 375 mg/m^2 on Dosing Day 30 and Day 58 | Dosing Day 58 | 43.00 hr |
Secondary
Serum Decay Half-Life (t1/2) of Total Calicheamicin (Conjugated Plus Unconjugated) in Participants Receiving Inotuzumab Ozogamicin MTD + Rituximab 375 mg/m^2 on Dosing Day 30 and Day 58
Termnial half-life (t½): Loge(2)/kel, where kel is the terminal phase rate constant calculated by a linear regression of the log-linear concentration-time curve. Study Days Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57 and Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85 correspond to Dosing Day 30 for Cycle 2 and Dosing Day 58 for Cycle 3.
Time frame: Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57; Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85
Population: Pk population
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| INOTUZUMAB OZOGAMICIN + RITUXIMAB 375 MG/M^2 | Serum Decay Half-Life (t1/2) of Total Calicheamicin (Conjugated Plus Unconjugated) in Participants Receiving Inotuzumab Ozogamicin MTD + Rituximab 375 mg/m^2 on Dosing Day 30 and Day 58 | Dosing Day 30 | 126.5 hr |
| INOTUZUMAB OZOGAMICIN + RITUXIMAB 375 MG/M^2 | Serum Decay Half-Life (t1/2) of Total Calicheamicin (Conjugated Plus Unconjugated) in Participants Receiving Inotuzumab Ozogamicin MTD + Rituximab 375 mg/m^2 on Dosing Day 30 and Day 58 | Dosing Day 58 | 176.0 hr |
Secondary
Steady-state Volume of Distribution (Vss) of Inotuzumab Ozogamicin in Serum in Participants Receiving Inotuzumab MTD+Rituximab 375 mg/m^2 on Dosing Day 30 and Day 58
Vss of inotuzumab ozogamicin on Dosing Days 30 and 58 were reported. Vss=CL\*MRT (mean residence time). Study Days Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57 and Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85 correspond to Dosing Day 30 for Cycle 2 and Dosing Day 58 for Cycle 3.
Time frame: Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57; Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85
Population: PK population
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| INOTUZUMAB OZOGAMICIN + RITUXIMAB 375 MG/M^2 | Steady-state Volume of Distribution (Vss) of Inotuzumab Ozogamicin in Serum in Participants Receiving Inotuzumab MTD+Rituximab 375 mg/m^2 on Dosing Day 30 and Day 58 | Dosing Day 30 | 4.860 L | Geometric Coefficient of Variation 37 |
| INOTUZUMAB OZOGAMICIN + RITUXIMAB 375 MG/M^2 | Steady-state Volume of Distribution (Vss) of Inotuzumab Ozogamicin in Serum in Participants Receiving Inotuzumab MTD+Rituximab 375 mg/m^2 on Dosing Day 30 and Day 58 | Dosing Day 58 | 5.183 L | Geometric Coefficient of Variation 38 |
Secondary
Steady-state Volume (Vss) of Inotuzumab Ozogamicin Antibody Distribution in Participants Receiving Inotuzumab Ozogamicin MTD + Rituximab 375 mg/m^2 on Dosing Day 30 and Day 58
Vss: Steady-state volume of distribution CL\*MRT of inotuzumab ozogamicin Day 30 for Cycle 2; and Day 58 for Cycle 3. Study Days Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57 and Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85 correspond to Dosing Day 30 for Cycle 2 and Dosing Day 58 for Cycle 3.
Time frame: Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57; Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85
Population: PK population
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| INOTUZUMAB OZOGAMICIN + RITUXIMAB 375 MG/M^2 | Steady-state Volume (Vss) of Inotuzumab Ozogamicin Antibody Distribution in Participants Receiving Inotuzumab Ozogamicin MTD + Rituximab 375 mg/m^2 on Dosing Day 30 and Day 58 | Dosing Day 30 | 5.283 L | Geometric Coefficient of Variation 29 |
| INOTUZUMAB OZOGAMICIN + RITUXIMAB 375 MG/M^2 | Steady-state Volume (Vss) of Inotuzumab Ozogamicin Antibody Distribution in Participants Receiving Inotuzumab Ozogamicin MTD + Rituximab 375 mg/m^2 on Dosing Day 30 and Day 58 | Dosing Day 58 | 4.952 L | Geometric Coefficient of Variation 34 |
Secondary
Steady-state Volume (Vss) of Total Calicheamicin (Conjugated Plus Unconjugated) Distribution in Participants Receiving Inotuzumab Ozogamicin MTD + Rituximab 375 mg/m^2 on Dosing Day 30 and Day 58
Vss: Steady-state volume of distribution CL\*MRT of inotuzumab ozogamicin Day 30 for Cycle 2; and Day 58 for Cycle 3. Study Days Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57 and Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85 correspond to Dosing Day 30 for Cycle 2 and Dosing Day 58 for Cycle 3.
Time frame: Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57; Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85
Population: PK population
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| INOTUZUMAB OZOGAMICIN + RITUXIMAB 375 MG/M^2 | Steady-state Volume (Vss) of Total Calicheamicin (Conjugated Plus Unconjugated) Distribution in Participants Receiving Inotuzumab Ozogamicin MTD + Rituximab 375 mg/m^2 on Dosing Day 30 and Day 58 | Dosing Day 30 | 72.95 L | Geometric Coefficient of Variation 35 |
| INOTUZUMAB OZOGAMICIN + RITUXIMAB 375 MG/M^2 | Steady-state Volume (Vss) of Total Calicheamicin (Conjugated Plus Unconjugated) Distribution in Participants Receiving Inotuzumab Ozogamicin MTD + Rituximab 375 mg/m^2 on Dosing Day 30 and Day 58 | Dosing Day 58 | 75.81 L | Geometric Coefficient of Variation 26 |
Secondary
Time of Observed Maximum Concentration (Tmax) of Total Calicheamicin (Conjugated+Unconjugated) in Participants Receiving Inotuzumab Ozogamicin MTD + Rituximab 375 mg/m^2 on Dosing Day 1, Day 30 and Day 58
Tmax: Time at which Cmax occurs. Observed directly from data as time of first occurrence. Study Days Cycle 1, Days 1 (0 hour), 2 (0, 1, 4 hours), 4, 8, 10, 15, and 29; Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57; and Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85 correspond to Dosing Day 1 for Cycle 1; Dosing Day 30 for Cycle 2; and Dosing Day 58 for Cycle 3.
Time frame: Cycle 1, Days 1 (0 hour), 2 (0, 1, 4 hours), 4, 8, 10, 15, and 29; Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57; Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85
Population: PK population
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| INOTUZUMAB OZOGAMICIN + RITUXIMAB 375 MG/M^2 | Time of Observed Maximum Concentration (Tmax) of Total Calicheamicin (Conjugated+Unconjugated) in Participants Receiving Inotuzumab Ozogamicin MTD + Rituximab 375 mg/m^2 on Dosing Day 1, Day 30 and Day 58 | Dosing Day 1 | 1.05 hr |
| INOTUZUMAB OZOGAMICIN + RITUXIMAB 375 MG/M^2 | Time of Observed Maximum Concentration (Tmax) of Total Calicheamicin (Conjugated+Unconjugated) in Participants Receiving Inotuzumab Ozogamicin MTD + Rituximab 375 mg/m^2 on Dosing Day 1, Day 30 and Day 58 | Dosing Day 30 | 1.26 hr |
| INOTUZUMAB OZOGAMICIN + RITUXIMAB 375 MG/M^2 | Time of Observed Maximum Concentration (Tmax) of Total Calicheamicin (Conjugated+Unconjugated) in Participants Receiving Inotuzumab Ozogamicin MTD + Rituximab 375 mg/m^2 on Dosing Day 1, Day 30 and Day 58 | Dosing Day 58 | 1.38 hr |
Secondary
Time of Observed Maximum Concentration (Tmax) of Unconjugated Calicheamicin in Participants Receiving Inotuzumab Ozogamicin + Rituximab on Dosing Day 1, Day 30 and Day 58
Tmax: Time at which Cmax occurs. Observed directly from data as time of first occurrence. Study Days Cycle 1, Days 1 (0 hour), 2 (0, 1, 4 hours), 4, 8, 10, 15, and 29; Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57; and Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85 correspond to Dosing Day 1 for Cycle 1; Dosing Day 30 for Cycle 2; and Dosing Day 58 for Cycle 3.
Time frame: Cycle 1, Days 1 (0 hour), 2 (0, 1, 4 hours), 4, 8, 10, 15, and 29; Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57; Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85
Population: PK population
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| INOTUZUMAB OZOGAMICIN + RITUXIMAB 375 MG/M^2 | Time of Observed Maximum Concentration (Tmax) of Unconjugated Calicheamicin in Participants Receiving Inotuzumab Ozogamicin + Rituximab on Dosing Day 1, Day 30 and Day 58 | Dosing Day 1 | 1.38 hr |
| INOTUZUMAB OZOGAMICIN + RITUXIMAB 375 MG/M^2 | Time of Observed Maximum Concentration (Tmax) of Unconjugated Calicheamicin in Participants Receiving Inotuzumab Ozogamicin + Rituximab on Dosing Day 1, Day 30 and Day 58 | Dosing Day 30 | 4.00 hr |
| INOTUZUMAB OZOGAMICIN + RITUXIMAB 375 MG/M^2 | Time of Observed Maximum Concentration (Tmax) of Unconjugated Calicheamicin in Participants Receiving Inotuzumab Ozogamicin + Rituximab on Dosing Day 1, Day 30 and Day 58 | Dosing Day 58 | 3.42 hr |
Secondary
Time of the Last Quantifiable Concentration in a Dosing Interval (Tlast) of Serum Inotuzumab Ozogamicin Antibody in Participants Receiving Inotuzumab Ozogamicin MTD + Rituximab 375 mg/m^2 on Dosing Day 1, Day 30 and Day 58
Tlast: Time of last quantifiable concentration. Observed directly from data. Study Days Cycle 1, Days 1 (0 hour), 2 (0, 1, 4 hours), 4, 8, 10, 15, and 29; Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57; and Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85 correspond to Dosing Day 1 for Cycle 1; Dosing Day 30 for Cycle 2; and Dosing Day 58 for Cycle 3.
Time frame: Cycle 1, Days 1 (0 hour), 2 (0, 1, 4 hours), 4, 8, 10, 15, and 29; Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57; Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85
Population: PK population
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| INOTUZUMAB OZOGAMICIN + RITUXIMAB 375 MG/M^2 | Time of the Last Quantifiable Concentration in a Dosing Interval (Tlast) of Serum Inotuzumab Ozogamicin Antibody in Participants Receiving Inotuzumab Ozogamicin MTD + Rituximab 375 mg/m^2 on Dosing Day 1, Day 30 and Day 58 | Dosing Day 1 | 190 hr |
| INOTUZUMAB OZOGAMICIN + RITUXIMAB 375 MG/M^2 | Time of the Last Quantifiable Concentration in a Dosing Interval (Tlast) of Serum Inotuzumab Ozogamicin Antibody in Participants Receiving Inotuzumab Ozogamicin MTD + Rituximab 375 mg/m^2 on Dosing Day 1, Day 30 and Day 58 | Dosing Day 30 | 310 hr |
| INOTUZUMAB OZOGAMICIN + RITUXIMAB 375 MG/M^2 | Time of the Last Quantifiable Concentration in a Dosing Interval (Tlast) of Serum Inotuzumab Ozogamicin Antibody in Participants Receiving Inotuzumab Ozogamicin MTD + Rituximab 375 mg/m^2 on Dosing Day 1, Day 30 and Day 58 | Dosing Day 58 | 312 hr |
Secondary
Time of the Last Quantifiable Concentration in a Dosing Interval (Tlast) of Total Calicheamicin (Conjugated Plus Unconjugated) in Participants Receiving Inotuzumab Ozogamicin MTD + Rituximab 375 mg/m^2 on Dosing Day 1, Day 30 and Day 58
Tlast: Time of last quantifiable concentration. Observed directly from data. Study Days Cycle 1, Days 1 (0 hour), 2 (0, 1, 4 hours), 4, 8, 10, 15, and 29; Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57; and Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85 correspond to Dosing Day 1 for Cycle 1; Dosing Day 30 for Cycle 2; and Dosing Day 58 for Cycle 3.
Time frame: Cycle 1, Days 1 (0 hour), 2 (0, 1, 4 hours), 4, 8, 10, 15, and 29; Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57; Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85
Population: PK population
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| INOTUZUMAB OZOGAMICIN + RITUXIMAB 375 MG/M^2 | Time of the Last Quantifiable Concentration in a Dosing Interval (Tlast) of Total Calicheamicin (Conjugated Plus Unconjugated) in Participants Receiving Inotuzumab Ozogamicin MTD + Rituximab 375 mg/m^2 on Dosing Day 1, Day 30 and Day 58 | Dosing Day 1 | 149 hr |
| INOTUZUMAB OZOGAMICIN + RITUXIMAB 375 MG/M^2 | Time of the Last Quantifiable Concentration in a Dosing Interval (Tlast) of Total Calicheamicin (Conjugated Plus Unconjugated) in Participants Receiving Inotuzumab Ozogamicin MTD + Rituximab 375 mg/m^2 on Dosing Day 1, Day 30 and Day 58 | Dosing Day 30 | 312 hr |
| INOTUZUMAB OZOGAMICIN + RITUXIMAB 375 MG/M^2 | Time of the Last Quantifiable Concentration in a Dosing Interval (Tlast) of Total Calicheamicin (Conjugated Plus Unconjugated) in Participants Receiving Inotuzumab Ozogamicin MTD + Rituximab 375 mg/m^2 on Dosing Day 1, Day 30 and Day 58 | Dosing Day 58 | 458 hr |
Secondary
Time of the Last Quantifiable Concentration in a Dosing Interval (Tlast) of Unconjugated Calicheamicin in Participants Receiving Inotuzumab Ozogamicin MTD + Rituximab 375 mg/m^2 on Dosing Day 1, Day 30 and Day 58
Tlast: Time of last quantifiable concentration. Observed directly from data. Study Days Cycle 1, Days 1 (0 hour), 2 (0, 1, 4 hours), 4, 8, 10, 15, and 29; Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57; and Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85 correspond to Dosing Day 1 for Cycle 1; Dosing Day 30 for Cycle 2; and Dosing Day 58 for Cycle 3.
Time frame: Cycle 1, Days 1 (0 hour), 2 (0, 1, 4 hours), 4, 8, 10, 15, and 29; Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57; Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85
Population: PK population
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| INOTUZUMAB OZOGAMICIN + RITUXIMAB 375 MG/M^2 | Time of the Last Quantifiable Concentration in a Dosing Interval (Tlast) of Unconjugated Calicheamicin in Participants Receiving Inotuzumab Ozogamicin MTD + Rituximab 375 mg/m^2 on Dosing Day 1, Day 30 and Day 58 | Dosing Day 30 | 4.00 hr |
| INOTUZUMAB OZOGAMICIN + RITUXIMAB 375 MG/M^2 | Time of the Last Quantifiable Concentration in a Dosing Interval (Tlast) of Unconjugated Calicheamicin in Participants Receiving Inotuzumab Ozogamicin MTD + Rituximab 375 mg/m^2 on Dosing Day 1, Day 30 and Day 58 | Dosing Day 1 | 48.5 hr |
| INOTUZUMAB OZOGAMICIN + RITUXIMAB 375 MG/M^2 | Time of the Last Quantifiable Concentration in a Dosing Interval (Tlast) of Unconjugated Calicheamicin in Participants Receiving Inotuzumab Ozogamicin MTD + Rituximab 375 mg/m^2 on Dosing Day 1, Day 30 and Day 58 | Dosing Day 58 | 4.00 hr |
Secondary
Time of the Last Quantifiable Serum Concentration in a Dosing Interval (Tlast) of Inotuzumab Ozogamicin in Participants Receving Inotuzumab Ozogamicin MTD + Rituximab 375 mg/m^2 on Dosing Day 1, Day 30 and Day 58
Tlast of inotuzumab ozogamicin on Dosing Days 1, 30, and 58 was reported. Tlast: Time of last quantifiable concentration of inotuzumab ozogamicin. Observed directly from data. Study Days Cycle 1, Days 1 (0 hour), 2 (0, 1, 4 hours), 4, 8, 10, 15, and 29; Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57; and Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85 correspond to Dosing Day 1 for Cycle 1; Dosing Day 30 for Cycle 2; and Dosing Day 58 for Cycle 3.
Time frame: Cycle 1, Days 1 (0 hour), 2 (0, 1, 4 hours), 4, 8, 10, 15, and 29; Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57; Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85
Population: PK population
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| INOTUZUMAB OZOGAMICIN + RITUXIMAB 375 MG/M^2 | Time of the Last Quantifiable Serum Concentration in a Dosing Interval (Tlast) of Inotuzumab Ozogamicin in Participants Receving Inotuzumab Ozogamicin MTD + Rituximab 375 mg/m^2 on Dosing Day 1, Day 30 and Day 58 | Dosing Day 1 | 44.2 hr |
| INOTUZUMAB OZOGAMICIN + RITUXIMAB 375 MG/M^2 | Time of the Last Quantifiable Serum Concentration in a Dosing Interval (Tlast) of Inotuzumab Ozogamicin in Participants Receving Inotuzumab Ozogamicin MTD + Rituximab 375 mg/m^2 on Dosing Day 1, Day 30 and Day 58 | Dosing Day 30 | 53.9 hr |
| INOTUZUMAB OZOGAMICIN + RITUXIMAB 375 MG/M^2 | Time of the Last Quantifiable Serum Concentration in a Dosing Interval (Tlast) of Inotuzumab Ozogamicin in Participants Receving Inotuzumab Ozogamicin MTD + Rituximab 375 mg/m^2 on Dosing Day 1, Day 30 and Day 58 | Dosing Day 58 | 137 hr |
Secondary
Time to Reach Maximum Concentration (Tmax) of Inotuzumab Ozogamicin in Participants Receiving Inotuzumab Ozogamicin MTD + Rituximab 375 mg/m^2 on Dosing Day 1, Day 30 and Day 58
Tmax: Time at which Cmax occurs. Observed directly from data as time of first occurrence. Study Days Cycle 1, Days 1 (0 hour), 2 (0, 1, 4 hours), 4, 8, 10, 15, and 29; Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57; and Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85 correspond to Dosing Day 1 for Cycle 1; Dosing Day 30 for Cycle 2; and Dosing Day 58 for Cycle 3.
Time frame: Cycle 1, Days 1 (0 hour), 2 (0, 1, 4 hours), 4, 8, 10, 15, and 29; Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57; Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85
Population: PK population
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| INOTUZUMAB OZOGAMICIN + RITUXIMAB 375 MG/M^2 | Time to Reach Maximum Concentration (Tmax) of Inotuzumab Ozogamicin in Participants Receiving Inotuzumab Ozogamicin MTD + Rituximab 375 mg/m^2 on Dosing Day 1, Day 30 and Day 58 | Dosing Day 1 | 1.00 hr |
| INOTUZUMAB OZOGAMICIN + RITUXIMAB 375 MG/M^2 | Time to Reach Maximum Concentration (Tmax) of Inotuzumab Ozogamicin in Participants Receiving Inotuzumab Ozogamicin MTD + Rituximab 375 mg/m^2 on Dosing Day 1, Day 30 and Day 58 | Dosing Day 30 | 1.08 hr |
| INOTUZUMAB OZOGAMICIN + RITUXIMAB 375 MG/M^2 | Time to Reach Maximum Concentration (Tmax) of Inotuzumab Ozogamicin in Participants Receiving Inotuzumab Ozogamicin MTD + Rituximab 375 mg/m^2 on Dosing Day 1, Day 30 and Day 58 | Dosing Day 58 | 1.08 hr |
Secondary
Time to Reach Maximum Concentration (Tmax) of Serum Inotuzumab Ozogamicin Antibody in Participants Receiving Inotuzumab Ozogamicin MTD + Rituximab 375 mg/m^2 on Dosing Day 1, Day 30 and Day 58
Tmax: Time at which Cmax occurs. Observed directly from data as time of first occurrence. Study Days Cycle 1, Days 1 (0 hour), 2 (0, 1, 4 hours), 4, 8, 10, 15, and 29; Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57; and Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85 correspond to Dosing Day 1 for Cycle 1; Dosing Day 30 for Cycle 2; and Dosing Day 58 for Cycle 3.
Time frame: Cycle 1, Days 1 (0 hour), 2 (0, 1, 4 hours), 4, 8, 10, 15, and 29; Cycle 2, Days 30 (0, 1, 4 hours), 32, 36, 38, 43, 50, and 57; Cycle 3, Days 58 (0, 1, 4 hours), 60, 64, 66, 71, 78, and 85
Population: PK population
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| INOTUZUMAB OZOGAMICIN + RITUXIMAB 375 MG/M^2 | Time to Reach Maximum Concentration (Tmax) of Serum Inotuzumab Ozogamicin Antibody in Participants Receiving Inotuzumab Ozogamicin MTD + Rituximab 375 mg/m^2 on Dosing Day 1, Day 30 and Day 58 | Dosing Day 1 | 1.05 hr |
| INOTUZUMAB OZOGAMICIN + RITUXIMAB 375 MG/M^2 | Time to Reach Maximum Concentration (Tmax) of Serum Inotuzumab Ozogamicin Antibody in Participants Receiving Inotuzumab Ozogamicin MTD + Rituximab 375 mg/m^2 on Dosing Day 1, Day 30 and Day 58 | Dosing Day 30 | 1.17 hr |
| INOTUZUMAB OZOGAMICIN + RITUXIMAB 375 MG/M^2 | Time to Reach Maximum Concentration (Tmax) of Serum Inotuzumab Ozogamicin Antibody in Participants Receiving Inotuzumab Ozogamicin MTD + Rituximab 375 mg/m^2 on Dosing Day 1, Day 30 and Day 58 | Dosing Day 58 | 3.79 hr |