Lymphoma, B-Cell
Conditions
Keywords
B-cell Non-Hodgkin's Lymphoma, NHL
Brief summary
To assess the tolerability and the initial safety profile of Inotuzumab Ozogamicin (CMC-544) in combination with Rituximab in patients with B-Cell Non-Hodgkin's lymphoma (NHL).
Interventions
1.8 mg/m2, IV on day 2 of each 28 day cycle; up to 8 cycles unless PD, unacceptable toxicity, or subject's refusal occurs.
375 mg/m2, IV on day 1 of each 28 day cycle; up to 8 cycles unless PD, unacceptable toxicity, or subject's refusal occurs.
Sponsors
Pfizer
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
20 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* CD20 and CD22-positive, B-cell NHL which has progressed after 1 or 2 prior therapies. * Prior therapy must have contained at least one dose of Rituximab therapy. Patients can not be refractory to Rituximab (refractory = PD under treatment or within 6 month * Eastern Cooperative Oncology Group (ECOG) performance status: 0/ 1. * Patients must not have received previous radioimmunotherapy. * Patients tolerant to Rituximab. * Patients must not have received chemotherapy, cancer immunosuppressive therapy, growth factors (except erythropoietin), or investigational agents within 28 days before first dose of test article.
Exclusion criteria
* Candidate for potentially curative therapies * Subjects must not have received previous radioimmunotherapy. * Subjects with autologous hematopoietic stem cell transplant within the last 6 months
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Dose-limiting Toxicities (DLT) | Up to 28 days | A DLT was defined as the following drug-related adverse event which occurred during the first 28 days: 1) Any National Cancer Institute (NCI) Grade 3 or 4 nonhematologic toxicity (except Grade 3 nausea or vomiting without optimal treatment), 2) Febrile neutropenia, 3) Grade 4 absolute neutrophil count lasting \>=7 days, 4) Grade 4 thrombocytopenia lasting \>=3 days, 5) Grade 3 or 4 thrombocytopenia associated with a bleeding episode requiring platelet transfusion, 6)Delayed recovery (to grade \<=1 or baseline, except alopecia) from a drug-related toxicity that delayed the next dose \>2 weeks |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Objective Response: Evaluable Population | Up to 8 cycles (1 cycle = 28 days) | Number of participants with objective response of complete response (CR), complete response unconfirmed (CRu), or partial response (PR). Objective response included subjects with CR, CRu, and PR. Response criteria for Non-Hodgkin's Lymphoma (NHL) were based on the 1999 NCI International Workshop to standardize response criteria for NHL. Per the criteria for Lymph node masses: CR, normal size; CRu, normal or \>75% decrease in the sum of the products of the greatest diameters (SPD); PR, normal or \>=50% decrease in the SPD. |
| Number of Participants With Objective Response: Intent-to-treat (ITT) Population | Up to 8 cycles (1 cycle = 28 days) | Number of participants with objective response of complete response (CR), complete response unconfirmed (CRu), or partial response (PR). Objective response included subjects with CR, CRu, and PR. Response criteria for Non-Hodgkin's Lymphoma (NHL) were based on the 1999 NCI International Workshop to standardize response criteria for NHL. Per the criteria for Lymph node masses: CR, normal size; CRu, normal or \>75% decrease in the sum of the products of the greatest diameters (SPD); PR, normal or \>=50% decrease in the SPD. |
| Progression-Free Survival (PFS) | Up to 591 days | The interval from the date of first administration of the test article until the first date on which relapsed disease, progressive disease (PD), or death was documented, censored at the last tumor evaluation date. Response criteria for Non-Hodgkin's Lymphoma (NHL) were based on the 1999 NCI International Workshop to standardize response criteria for NHL. Per the criteria for Lymph node masses: Relapse/PD, appearance of any new lesion or increased by \>=50% in the size. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Clearance (CL) of CMC-544, Total Calicheamicin, and G544 | Cycle 1, Cycle 2 and Cycle 3 at hour 0 (predose) and at hours 1 (before the end of infusion), 4, 48, 144,192, 312, 480, and 648 relative to the start of infusion of CMC-544 | The rate at which a drug is metabolized or eliminated by normal biological processes. |
| Volume of Distribution (Vss) of CMC-544, Total Calicheamicin, and G544 | Cycle 1, Cycle 2 and Cycle 3 at hour 0 (predose) and at hours 1 (before the end of infusion), 4, 48, 144,192, 312, 480, and 648 relative to the start of infusion of CMC-544 | The theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired blood concentration of a drug. |
| Maximum Observed Serum Concentration (Cmax) of CMC-544, Total Calicheamicin, and Anti-human CD22 Antibody (G544) | Cycle 1, Cycle 2 and Cycle 3 at hour 0 (predose) and at hours 1 (before the end of infusion), 4, 48, 144,192, 312, 480, and 648 relative to the start of infusion of CMC-544 | CMC-544 is composed of G544, an anti-human CD22 antibody, linked to a potent cytotoxic antitumor antibiotic called calicheamicin. CD22 is expressed on the malignant cells of the majority of B-lymphocyte malignancies. |
| Number of Participants With Positive Serum Antibody to Rituximab | Up to 8 Cycles (1 cycle = 28 days) | Antibody responses to rituximab |
| Number of Participants With Positive Serum Antibody to Inotuzumab Ozogamicin (CMC-544) | Up to 8 Cycles (1 cycle = 28 days) | Antibody responses to CMC-544 |
| Serum Decay Half-Life (t1/2) of CMC-544, Total Calicheamicin, and G544 | Cycle 1, Cycle 2 and Cycle 3 at hour 0 (predose) and at hours 1 (before the end of infusion), 4, 48, 144,192, 312, 480, and 648 relative to the start of infusion of CMC-544 | The time measured for the serum concentration to decrease by one half. |
| Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) of CMC-544, Total Calicheamicin, and G544 | Cycle 1, Cycle 2 and Cycle 3 at hour 0 (predose) and at hours 1 (before the end of infusion), 4, 48, 144,192, 312, 480, and 648 relative to the start of infusion of CMC-544 | AUClast= Area under the serum concentration versus time curve from time zero (pre-dose) to time of last measured concentration. |
| Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUC∞) of CMC-544, Total Calicheamicin, and G544 | Cycle 1, Cycle 2 and Cycle 3 at hour 0 (predose) and at hours 1 (before the end of infusion), 4, 48, 144,192, 312, 480, and 648 relative to the start of infusion of CMC-544 | AUC∞ = Area under the serum concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (∞). It is obtained from AUC (0 - t) plus AUC (t - ∞). |
Countries
Japan
Participant flow
Pre-assignment details
Six consecutive patients were enrolled as the first cohort. The dose and administration were considered to be reasonable if \<=2 participants in the first cohort experienced a dose limiting toxicity (DLT), and an additional 4 subjects were to be enrolled as the expanded cohort for a total 10 participants.
Participants by arm
| Arm | Count |
|---|---|
| CMC-544 1.8 mg/m^2 + Rituximab 375 mg/m^2 Participants were treated with intravenous rituximab (375 mg/m\^2) followed by intravenous CMC-544 (1.8 mg/m\^2) every 28 days (±2 days) for 4 cycles (1 cycle = 28 days), and participants with at least stable disease (SD) after the fourth cycle received CMC-544 up to 8 cycles unless they experienced progressive disease (PD) or an unacceptable toxicity, or withdrew consent. | 10 |
| Total | 10 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 5 |
| Overall Study | Withdrawal by Subject | 1 |
Baseline characteristics
| Characteristic | CMC-544 1.8 mg/m^2 + Rituximab 375 mg/m^2 |
|---|---|
| Age, Continuous | 60.20 years STANDARD_DEVIATION 10.96 |
| Sex: Female, Male Female | 5 Participants |
| Sex: Female, Male Male | 5 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 10 / 10 |
| serious Total, serious adverse events | 0 / 10 |
Outcome results
Primary
Number of Participants With Dose-limiting Toxicities (DLT)
A DLT was defined as the following drug-related adverse event which occurred during the first 28 days: 1) Any National Cancer Institute (NCI) Grade 3 or 4 nonhematologic toxicity (except Grade 3 nausea or vomiting without optimal treatment), 2) Febrile neutropenia, 3) Grade 4 absolute neutrophil count lasting \>=7 days, 4) Grade 4 thrombocytopenia lasting \>=3 days, 5) Grade 3 or 4 thrombocytopenia associated with a bleeding episode requiring platelet transfusion, 6)Delayed recovery (to grade \<=1 or baseline, except alopecia) from a drug-related toxicity that delayed the next dose \>2 weeks
Time frame: Up to 28 days
Population: The first cohort was analyzed for DLT.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| CMC-544 1.8 mg/m^2 + Rituximab 375 mg/m^2 | Number of Participants With Dose-limiting Toxicities (DLT) | 2 Participants |
Secondary
Number of Participants With Objective Response: Evaluable Population
Number of participants with objective response of complete response (CR), complete response unconfirmed (CRu), or partial response (PR). Objective response included subjects with CR, CRu, and PR. Response criteria for Non-Hodgkin's Lymphoma (NHL) were based on the 1999 NCI International Workshop to standardize response criteria for NHL. Per the criteria for Lymph node masses: CR, normal size; CRu, normal or \>75% decrease in the sum of the products of the greatest diameters (SPD); PR, normal or \>=50% decrease in the SPD.
Time frame: Up to 8 cycles (1 cycle = 28 days)
Population: The evaluable population included all participants who received at least 2 doses of the test article and who had a baseline tumor CT scan and underwent at least 1 postbaseline tumor assessment for anticancer clinical activity.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| CMC-544 1.8 mg/m^2 + Rituximab 375 mg/m^2 | Number of Participants With Objective Response: Evaluable Population | Complete response (CR) | 6 Participants |
| CMC-544 1.8 mg/m^2 + Rituximab 375 mg/m^2 | Number of Participants With Objective Response: Evaluable Population | Complete response unconfirmed (CRu) | 1 Participants |
| CMC-544 1.8 mg/m^2 + Rituximab 375 mg/m^2 | Number of Participants With Objective Response: Evaluable Population | Partial response (PR) | 0 Participants |
| CMC-544 1.8 mg/m^2 + Rituximab 375 mg/m^2 | Number of Participants With Objective Response: Evaluable Population | Objective Response (CR+CRu+PR) | 7 Participants |
Secondary
Number of Participants With Objective Response: Intent-to-treat (ITT) Population
Number of participants with objective response of complete response (CR), complete response unconfirmed (CRu), or partial response (PR). Objective response included subjects with CR, CRu, and PR. Response criteria for Non-Hodgkin's Lymphoma (NHL) were based on the 1999 NCI International Workshop to standardize response criteria for NHL. Per the criteria for Lymph node masses: CR, normal size; CRu, normal or \>75% decrease in the sum of the products of the greatest diameters (SPD); PR, normal or \>=50% decrease in the SPD.
Time frame: Up to 8 cycles (1 cycle = 28 days)
Population: The ITT population included all participants who were enrolled in the intended dose scheme.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| CMC-544 1.8 mg/m^2 + Rituximab 375 mg/m^2 | Number of Participants With Objective Response: Intent-to-treat (ITT) Population | Complete response (CR) | 6 Participants |
| CMC-544 1.8 mg/m^2 + Rituximab 375 mg/m^2 | Number of Participants With Objective Response: Intent-to-treat (ITT) Population | Complete response unconfirmed (CRu) | 1 Participants |
| CMC-544 1.8 mg/m^2 + Rituximab 375 mg/m^2 | Number of Participants With Objective Response: Intent-to-treat (ITT) Population | Partial response (PR) | 1 Participants |
| CMC-544 1.8 mg/m^2 + Rituximab 375 mg/m^2 | Number of Participants With Objective Response: Intent-to-treat (ITT) Population | Objective Response (CR+CRu+PR) | 8 Participants |
Secondary
Progression-Free Survival (PFS)
The interval from the date of first administration of the test article until the first date on which relapsed disease, progressive disease (PD), or death was documented, censored at the last tumor evaluation date. Response criteria for Non-Hodgkin's Lymphoma (NHL) were based on the 1999 NCI International Workshop to standardize response criteria for NHL. Per the criteria for Lymph node masses: Relapse/PD, appearance of any new lesion or increased by \>=50% in the size.
Time frame: Up to 591 days
Population: The evaluable population included all participants who received at least 2 doses of the test article and who had a baseline tumor computed tomography (CT) scan and underwent at least 1 postbaseline tumor assessment for anticancer clinical activity.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| CMC-544 1.8 mg/m^2 + Rituximab 375 mg/m^2 | Progression-Free Survival (PFS) | NA weeks |
Other Pre-specified
Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUC∞) of CMC-544, Total Calicheamicin, and G544
AUC∞ = Area under the serum concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (∞). It is obtained from AUC (0 - t) plus AUC (t - ∞).
Time frame: Cycle 1, Cycle 2 and Cycle 3 at hour 0 (predose) and at hours 1 (before the end of infusion), 4, 48, 144,192, 312, 480, and 648 relative to the start of infusion of CMC-544
Population: Pharmacokinetic population included participants who received at least 1 dose of the test article and with serum concentrations available. Number Analyzed = number of participants with the pertinent parameters calculated at the visit.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| CMC-544 1.8 mg/m^2 + Rituximab 375 mg/m^2 | Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUC∞) of CMC-544, Total Calicheamicin, and G544 | CMC-544: Cycle 1 | 22300 ng*hour/mL | Standard Deviation 2850 |
| CMC-544 1.8 mg/m^2 + Rituximab 375 mg/m^2 | Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUC∞) of CMC-544, Total Calicheamicin, and G544 | CMC-544: Cycle 2 | 34800 ng*hour/mL | Standard Deviation 12200 |
| CMC-544 1.8 mg/m^2 + Rituximab 375 mg/m^2 | Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUC∞) of CMC-544, Total Calicheamicin, and G544 | CMC-544: Cycle 3 | 54800 ng*hour/mL | Standard Deviation 7070 |
| CMC-544 1.8 mg/m^2 + Rituximab 375 mg/m^2 | Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUC∞) of CMC-544, Total Calicheamicin, and G544 | Total Calicheamicin: Cycle 1 | 4060 ng*hour/mL | Standard Deviation 1100 |
| CMC-544 1.8 mg/m^2 + Rituximab 375 mg/m^2 | Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUC∞) of CMC-544, Total Calicheamicin, and G544 | Total Calicheamicin: Cycle 2 | 7460 ng*hour/mL | Standard Deviation 2540 |
| CMC-544 1.8 mg/m^2 + Rituximab 375 mg/m^2 | Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUC∞) of CMC-544, Total Calicheamicin, and G544 | Total Calicheamicin: Cycle 3 | 12700 ng*hour/mL | Standard Deviation 5400 |
| CMC-544 1.8 mg/m^2 + Rituximab 375 mg/m^2 | Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUC∞) of CMC-544, Total Calicheamicin, and G544 | G544: Cycle 1 | 47700 ng*hour/mL | Standard Deviation 14300 |
| CMC-544 1.8 mg/m^2 + Rituximab 375 mg/m^2 | Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUC∞) of CMC-544, Total Calicheamicin, and G544 | G544: Cycle 2 | 92300 ng*hour/mL | Standard Deviation 26300 |
| CMC-544 1.8 mg/m^2 + Rituximab 375 mg/m^2 | Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUC∞) of CMC-544, Total Calicheamicin, and G544 | G544: Cycle 3 | 138000 ng*hour/mL | Standard Deviation 42600 |
Other Pre-specified
Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) of CMC-544, Total Calicheamicin, and G544
AUClast= Area under the serum concentration versus time curve from time zero (pre-dose) to time of last measured concentration.
Time frame: Cycle 1, Cycle 2 and Cycle 3 at hour 0 (predose) and at hours 1 (before the end of infusion), 4, 48, 144,192, 312, 480, and 648 relative to the start of infusion of CMC-544
Population: Pharmacokinetic population included participants who received at least 1 dose of the test article and with serum concentrations available. Number Analyzed = number of participants with the pertinent parameters calculated at the visit.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| CMC-544 1.8 mg/m^2 + Rituximab 375 mg/m^2 | Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) of CMC-544, Total Calicheamicin, and G544 | CMC-544: Cycle 1 | 12300 ng*hour/mL | Standard Deviation 6200 |
| CMC-544 1.8 mg/m^2 + Rituximab 375 mg/m^2 | Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) of CMC-544, Total Calicheamicin, and G544 | CMC-544: Cycle 2 | 27000 ng*hour/mL | Standard Deviation 7450 |
| CMC-544 1.8 mg/m^2 + Rituximab 375 mg/m^2 | Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) of CMC-544, Total Calicheamicin, and G544 | CMC-544: Cycle 3 | 50100 ng*hour/mL | Standard Deviation 6390 |
| CMC-544 1.8 mg/m^2 + Rituximab 375 mg/m^2 | Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) of CMC-544, Total Calicheamicin, and G544 | Total Calicheamicin: Cycle 1 | 2850 ng*hour/mL | Standard Deviation 1400 |
| CMC-544 1.8 mg/m^2 + Rituximab 375 mg/m^2 | Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) of CMC-544, Total Calicheamicin, and G544 | Total Calicheamicin: Cycle 2 | 6490 ng*hour/mL | Standard Deviation 2250 |
| CMC-544 1.8 mg/m^2 + Rituximab 375 mg/m^2 | Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) of CMC-544, Total Calicheamicin, and G544 | Total Calicheamicin: Cycle 3 | 10700 ng*hour/mL | Standard Deviation 4750 |
| CMC-544 1.8 mg/m^2 + Rituximab 375 mg/m^2 | Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) of CMC-544, Total Calicheamicin, and G544 | G544: Cycle 1 | 38400 ng*hour/mL | Standard Deviation 16300 |
| CMC-544 1.8 mg/m^2 + Rituximab 375 mg/m^2 | Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) of CMC-544, Total Calicheamicin, and G544 | G544: Cycle 2 | 84900 ng*hour/mL | Standard Deviation 23400 |
| CMC-544 1.8 mg/m^2 + Rituximab 375 mg/m^2 | Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) of CMC-544, Total Calicheamicin, and G544 | G544: Cycle 3 | 127000 ng*hour/mL | Standard Deviation 44800 |
Other Pre-specified
Clearance (CL) of CMC-544, Total Calicheamicin, and G544
The rate at which a drug is metabolized or eliminated by normal biological processes.
Time frame: Cycle 1, Cycle 2 and Cycle 3 at hour 0 (predose) and at hours 1 (before the end of infusion), 4, 48, 144,192, 312, 480, and 648 relative to the start of infusion of CMC-544
Population: Pharmacokinetic population included participants who received at least 1 dose of the test article and with serum concentrations available. Number Analyzed = number of participants with the pertinent parameters calculated at the visit.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| CMC-544 1.8 mg/m^2 + Rituximab 375 mg/m^2 | Clearance (CL) of CMC-544, Total Calicheamicin, and G544 | CMC-544: Cycle 1 | 0.120 L/hour | Standard Deviation 0.0185 |
| CMC-544 1.8 mg/m^2 + Rituximab 375 mg/m^2 | Clearance (CL) of CMC-544, Total Calicheamicin, and G544 | CMC-544: Cycle 2 | 0.0782 L/hour | Standard Deviation 0.0192 |
| CMC-544 1.8 mg/m^2 + Rituximab 375 mg/m^2 | Clearance (CL) of CMC-544, Total Calicheamicin, and G544 | CMC-544: Cycle 3 | 0.0499 L/hour | Standard Deviation 0.0012 |
| CMC-544 1.8 mg/m^2 + Rituximab 375 mg/m^2 | Clearance (CL) of CMC-544, Total Calicheamicin, and G544 | Total Calicheamicin: Cycle 1 | 0.746 L/hour | Standard Deviation 0.212 |
| CMC-544 1.8 mg/m^2 + Rituximab 375 mg/m^2 | Clearance (CL) of CMC-544, Total Calicheamicin, and G544 | Total Calicheamicin: Cycle 2 | 0.424 L/hour | Standard Deviation 0.133 |
| CMC-544 1.8 mg/m^2 + Rituximab 375 mg/m^2 | Clearance (CL) of CMC-544, Total Calicheamicin, and G544 | Total Calicheamicin: Cycle 3 | 0.249 L/hour | Standard Deviation 0.0686 |
| CMC-544 1.8 mg/m^2 + Rituximab 375 mg/m^2 | Clearance (CL) of CMC-544, Total Calicheamicin, and G544 | G544: Cycle 1 | 0.0662 L/hour | Standard Deviation 0.0236 |
| CMC-544 1.8 mg/m^2 + Rituximab 375 mg/m^2 | Clearance (CL) of CMC-544, Total Calicheamicin, and G544 | G544: Cycle 2 | 0.0331 L/hour | Standard Deviation 0.0077 |
| CMC-544 1.8 mg/m^2 + Rituximab 375 mg/m^2 | Clearance (CL) of CMC-544, Total Calicheamicin, and G544 | G544: Cycle 3 | 0.0213 L/hour | Standard Deviation 0.0062 |
Other Pre-specified
Maximum Observed Serum Concentration (Cmax) of CMC-544, Total Calicheamicin, and Anti-human CD22 Antibody (G544)
CMC-544 is composed of G544, an anti-human CD22 antibody, linked to a potent cytotoxic antitumor antibiotic called calicheamicin. CD22 is expressed on the malignant cells of the majority of B-lymphocyte malignancies.
Time frame: Cycle 1, Cycle 2 and Cycle 3 at hour 0 (predose) and at hours 1 (before the end of infusion), 4, 48, 144,192, 312, 480, and 648 relative to the start of infusion of CMC-544
Population: Phamacokinetic population included participants who received at least 1 dose of the test article and with serum concentrations available. Number Analyzed = number of participants with the pertinent parameters calculated at the visit.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| CMC-544 1.8 mg/m^2 + Rituximab 375 mg/m^2 | Maximum Observed Serum Concentration (Cmax) of CMC-544, Total Calicheamicin, and Anti-human CD22 Antibody (G544) | CMC-544: Cycle 1 | 559 ng/mL | Standard Deviation 136 |
| CMC-544 1.8 mg/m^2 + Rituximab 375 mg/m^2 | Maximum Observed Serum Concentration (Cmax) of CMC-544, Total Calicheamicin, and Anti-human CD22 Antibody (G544) | CMC-544: Cycle 2 | 822 ng/mL | Standard Deviation 152 |
| CMC-544 1.8 mg/m^2 + Rituximab 375 mg/m^2 | Maximum Observed Serum Concentration (Cmax) of CMC-544, Total Calicheamicin, and Anti-human CD22 Antibody (G544) | CMC-544: Cycle 3 | 958 ng/mL | Standard Deviation 64 |
| CMC-544 1.8 mg/m^2 + Rituximab 375 mg/m^2 | Maximum Observed Serum Concentration (Cmax) of CMC-544, Total Calicheamicin, and Anti-human CD22 Antibody (G544) | Total Calicheamicin: Cycle 1 | 67.7 ng/mL | Standard Deviation 14.9 |
| CMC-544 1.8 mg/m^2 + Rituximab 375 mg/m^2 | Maximum Observed Serum Concentration (Cmax) of CMC-544, Total Calicheamicin, and Anti-human CD22 Antibody (G544) | Total Calicheamicin: Cycle 2 | 80.2 ng/mL | Standard Deviation 11.3 |
| CMC-544 1.8 mg/m^2 + Rituximab 375 mg/m^2 | Maximum Observed Serum Concentration (Cmax) of CMC-544, Total Calicheamicin, and Anti-human CD22 Antibody (G544) | Total Calicheamicin: Cycle 3 | 96.6 ng/mL | Standard Deviation 2.89 |
| CMC-544 1.8 mg/m^2 + Rituximab 375 mg/m^2 | Maximum Observed Serum Concentration (Cmax) of CMC-544, Total Calicheamicin, and Anti-human CD22 Antibody (G544) | G544: Cycle 1 | 839 ng/mL | Standard Deviation 157 |
| CMC-544 1.8 mg/m^2 + Rituximab 375 mg/m^2 | Maximum Observed Serum Concentration (Cmax) of CMC-544, Total Calicheamicin, and Anti-human CD22 Antibody (G544) | G544: Cycle 2 | 1110 ng/mL | Standard Deviation 88.9 |
| CMC-544 1.8 mg/m^2 + Rituximab 375 mg/m^2 | Maximum Observed Serum Concentration (Cmax) of CMC-544, Total Calicheamicin, and Anti-human CD22 Antibody (G544) | G544: Cycle 3 | 1210 ng/mL | Standard Deviation 177 |
Other Pre-specified
Number of Participants With Positive Serum Antibody to Inotuzumab Ozogamicin (CMC-544)
Antibody responses to CMC-544
Time frame: Up to 8 Cycles (1 cycle = 28 days)
Population: The intent-to-treat (ITT) population included all participants in the intended dose scheme.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| CMC-544 1.8 mg/m^2 + Rituximab 375 mg/m^2 | Number of Participants With Positive Serum Antibody to Inotuzumab Ozogamicin (CMC-544) | Screening | 1 Participants |
| CMC-544 1.8 mg/m^2 + Rituximab 375 mg/m^2 | Number of Participants With Positive Serum Antibody to Inotuzumab Ozogamicin (CMC-544) | End of Treatment | 0 Participants |
Other Pre-specified
Number of Participants With Positive Serum Antibody to Rituximab
Antibody responses to rituximab
Time frame: Up to 8 Cycles (1 cycle = 28 days)
Population: The intent-to-treat (ITT) population included all participants in the intended dose scheme.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| CMC-544 1.8 mg/m^2 + Rituximab 375 mg/m^2 | Number of Participants With Positive Serum Antibody to Rituximab | Screening | 0 Participants |
| CMC-544 1.8 mg/m^2 + Rituximab 375 mg/m^2 | Number of Participants With Positive Serum Antibody to Rituximab | End of Treatment | 0 Participants |
Other Pre-specified
Serum Decay Half-Life (t1/2) of CMC-544, Total Calicheamicin, and G544
The time measured for the serum concentration to decrease by one half.
Time frame: Cycle 1, Cycle 2 and Cycle 3 at hour 0 (predose) and at hours 1 (before the end of infusion), 4, 48, 144,192, 312, 480, and 648 relative to the start of infusion of CMC-544
Population: Pharmacokinetic population included participants who received at least 1 dose of the test article and with serum concentrations available. Number Analyzed = number of participants with the pertinent parameters calculated at the visit.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| CMC-544 1.8 mg/m^2 + Rituximab 375 mg/m^2 | Serum Decay Half-Life (t1/2) of CMC-544, Total Calicheamicin, and G544 | CMC-544: Cycle 1 | 18.77 hours | Standard Deviation 1.09 |
| CMC-544 1.8 mg/m^2 + Rituximab 375 mg/m^2 | Serum Decay Half-Life (t1/2) of CMC-544, Total Calicheamicin, and G544 | CMC-544: Cycle 2 | 29.08 hours | Standard Deviation 21.79 |
| CMC-544 1.8 mg/m^2 + Rituximab 375 mg/m^2 | Serum Decay Half-Life (t1/2) of CMC-544, Total Calicheamicin, and G544 | CMC-544: Cycle 3 | 51.70 hours | Standard Deviation 20.59 |
| CMC-544 1.8 mg/m^2 + Rituximab 375 mg/m^2 | Serum Decay Half-Life (t1/2) of CMC-544, Total Calicheamicin, and G544 | Total Calicheamicin: Cycle 1 | 61.23 hours | Standard Deviation 34.84 |
| CMC-544 1.8 mg/m^2 + Rituximab 375 mg/m^2 | Serum Decay Half-Life (t1/2) of CMC-544, Total Calicheamicin, and G544 | Total Calicheamicin: Cycle 2 | 96.44 hours | Standard Deviation 31.31 |
| CMC-544 1.8 mg/m^2 + Rituximab 375 mg/m^2 | Serum Decay Half-Life (t1/2) of CMC-544, Total Calicheamicin, and G544 | Total Calicheamicin: Cycle 3 | 167.87 hours | Standard Deviation 72.85 |
| CMC-544 1.8 mg/m^2 + Rituximab 375 mg/m^2 | Serum Decay Half-Life (t1/2) of CMC-544, Total Calicheamicin, and G544 | G544: Cycle 1 | 67.14 hours | Standard Deviation 31.84 |
| CMC-544 1.8 mg/m^2 + Rituximab 375 mg/m^2 | Serum Decay Half-Life (t1/2) of CMC-544, Total Calicheamicin, and G544 | G544: Cycle 2 | 101.59 hours | Standard Deviation 34.08 |
| CMC-544 1.8 mg/m^2 + Rituximab 375 mg/m^2 | Serum Decay Half-Life (t1/2) of CMC-544, Total Calicheamicin, and G544 | G544: Cycle 3 | 127.57 hours | Standard Deviation 32.76 |
Other Pre-specified
Volume of Distribution (Vss) of CMC-544, Total Calicheamicin, and G544
The theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired blood concentration of a drug.
Time frame: Cycle 1, Cycle 2 and Cycle 3 at hour 0 (predose) and at hours 1 (before the end of infusion), 4, 48, 144,192, 312, 480, and 648 relative to the start of infusion of CMC-544
Population: Pharmacokinetic population included participants who received at least 1 dose of the test article and with serum concentrations available. Number Analyzed = number of participants with the pertinent parameters calculated at the visit.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| CMC-544 1.8 mg/m^2 + Rituximab 375 mg/m^2 | Volume of Distribution (Vss) of CMC-544, Total Calicheamicin, and G544 | CMC-544: Cycle 1 | 2.33 L | Standard Deviation 0.0763 |
| CMC-544 1.8 mg/m^2 + Rituximab 375 mg/m^2 | Volume of Distribution (Vss) of CMC-544, Total Calicheamicin, and G544 | CMC-544: Cycle 2 | 2.26 L | Standard Deviation 1.74 |
| CMC-544 1.8 mg/m^2 + Rituximab 375 mg/m^2 | Volume of Distribution (Vss) of CMC-544, Total Calicheamicin, and G544 | CMC-544: Cycle 3 | 3.02 L | Standard Deviation 1.23 |
| CMC-544 1.8 mg/m^2 + Rituximab 375 mg/m^2 | Volume of Distribution (Vss) of CMC-544, Total Calicheamicin, and G544 | Total Calicheamicin: Cycle 1 | 47.6 L | Standard Deviation 11.3 |
| CMC-544 1.8 mg/m^2 + Rituximab 375 mg/m^2 | Volume of Distribution (Vss) of CMC-544, Total Calicheamicin, and G544 | Total Calicheamicin: Cycle 2 | 45.6 L | Standard Deviation 7.04 |
| CMC-544 1.8 mg/m^2 + Rituximab 375 mg/m^2 | Volume of Distribution (Vss) of CMC-544, Total Calicheamicin, and G544 | Total Calicheamicin: Cycle 3 | 47.8 L | Standard Deviation 6.62 |
| CMC-544 1.8 mg/m^2 + Rituximab 375 mg/m^2 | Volume of Distribution (Vss) of CMC-544, Total Calicheamicin, and G544 | G544: Cycle 1 | 3.95 L | Standard Deviation 0.921 |
| CMC-544 1.8 mg/m^2 + Rituximab 375 mg/m^2 | Volume of Distribution (Vss) of CMC-544, Total Calicheamicin, and G544 | G544: Cycle 2 | 3.39 L | Standard Deviation 0.515 |
| CMC-544 1.8 mg/m^2 + Rituximab 375 mg/m^2 | Volume of Distribution (Vss) of CMC-544, Total Calicheamicin, and G544 | G544: Cycle 3 | 3.02 L | Standard Deviation 0.4 |