Acute Lymphoblastic Leukemia
Conditions
Brief summary
This is an open-label, single-arm, multicenter study in Chinese patients with relapsed or refractory CD22-positive B-cell ALL. The objective of the study is to confirm the efficacy, safety, and PK of inotuzumab ozogamicin in patients with relapsed or refractory B-cell ALL from mainland China.
Interventions
DRUGinotuzumab ozogamicin
Given IV
Sponsors
Pfizer
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Male or female participants, age 18 years or older at screening. * Relapsed or refractory CD22-positive ALL. * Subjects with Philadelphia chromosome-positive (Ph+) ALL must have failed standard treatment with at least one tyrosine kinase inhibitor. * Patients in Salvage 1 with late relapse should be deemed poor candidates for reinduction with initial therapy. * Patients with lymphoblastic lymphoma and bone marrow involvement ≥5% lymphoblasts by morphologic assessment. * ECOG performance status 0-2. * Adequate renal and hepatic function, and negative pregnancy test for women of childbearing potential.
Exclusion criteria
* Subjects with isolated extramedullary relapse or active central nervous system (CNS) leukemia. * Prior allogeneic hematopoietic stem cell transplant (HSCT) or other anti-CD22 immunotherapy within 4 months, or active graft versus host disease (GvHD) at study entry. * Evidence or history of veno-occlusive disease (VOD) or sinusoidal obstruction syndrome (SOS).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Complete Remission (CR) or Complete Remission With Incomplete Hematological Recovery (CRi) as Per Investigator's Assessment According to a Modified Cheson Criteria | From InO treatment initiation on Day 1 to CR or CRi (maximum up to 30.1 weeks of treatment exposure) | CR: disappearance of leukemia as indicated by \<5% marrow blasts and the absence of peripheral blood leukemic blasts, with recovery of hematopoiesis defined by absolute neutrophil count (ANC) \>=1000 per microliter (/mcL) and platelets \>=100,000/mcL. C1 extramedullary disease (EMD) status was required (disappearance of all measurable and non-measurable EMD with the exception of lesions for which following must be true: participants with at least 1 measurable lesion, all nodal masses \>1.5 centimeter (cm) in greatest transverse diameter (GTD) at baseline regressed to \<=1.5 cm in GTD and nodal masses \>=1 cm and \<=1.5 cm in GTD at baseline must have regressed to \<1 cm GTD or reduced by 75% in sum of products of greatest diameters (SPD). No new lesions. Spleen and other previously enlarged organs must have regressed in size and must not be palpable. All diseases were assessed using the same technique as at baseline. CRi: CR except with ANC \<1000/mcL and/or platelets \<100,000/mcL. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Minimal Residual Disease (MRD) Negativity Among Who Achieved CR/CRi | From CR/CRi till MRD negativity achieved (maximum up to 30.1 weeks of treatment exposure) | MRD negativity was defined as malignant B lymphocytes occurring at frequency \<10\^4. CR: disappearance of leukemia as indicated by \<5% marrow blasts and absence of peripheral blood leukemic blasts, with recovery of hematopoiesis defined by ANC \>=1000 per microliter (/mcL) and platelets \>=10\^5/mcL. C1 EMD status was required (disappearance of all measurable and non-measurable EMD with the exception of lesions for which following must be true: participants with at least 1 measurable lesion, all nodal masses \>1.5 cm in GTD at baseline regressed to \<=1.5 cm in GTD and nodal masses \>=1 cm and \<=1.5 cm in GTD at baseline must have regressed to \<1 cm GTD or reduced by 75% in SPD. No new lesions. Spleen and other previously enlarged organs must have regressed in size and must not be palpable. All diseases must be assessed using same technique as at baseline. CRi: CR except with ANC \<1000/mcL and/or platelets \<10\^5/mcL. |
| Progression-free Survival (PFS) | From date of first dose to the date of disease progression (objective progression, relapse from CR/CRi), or death due to any cause, whichever occurred first | PFS: from date of first dose to date of disease progression (objective progression, relapse from CR/CRi), or death due to any cause, whichever occurred first. CR: disappearance of leukemia as indicated by \<5% marrow blasts and absence of peripheral blood leukemic blasts, with recovery of hematopoiesis defined by ANC \>=1000 per microliter (/mcL) and platelets \>=10\^5/mcL. C1 EMD status was required (disappearance of all measurable and non-measurable EMD with the exception of lesions for which following must be true: participants with at least 1 measurable lesion, all nodal masses \>1.5 cm in GTD at baseline regressed to \<=1.5 cm in GTD and nodal masses \>=1 cm and \<=1.5 cm in GTD at baseline must have regressed to \<1 cm GTD or reduced by 75% in SPD. No new lesions. Spleen and other previously enlarged organs must have regressed in size and must not be palpable. All diseases must be assessed using same technique as at baseline. CRi: CR except with ANC \<1000/mcL and/or platelets \<10\^5/mcL. |
| Overall Survival (OS) | From date of first dose to the date of death due to any cause or censoring, whichever occurred first | OS was defined as the time from date of first dose to the date of death due to any cause. Participants without confirmation of death were to be censored on date of last contact. |
| Number of Participants Who Proceeded to Hematopoietic Stem Cell Transplantation (HSCT) | From InO treatment initiation till study completion | Participants who proceeded to HSCT was reported. HSCT is a procedure where multipotent hematopoietic stem cells are transplanted from sources such as bone marrow, peripheral blood, or umbilical cord blood. These stem cells can replicate inside a participant and produce additional normal blood cells. |
| Number of Participants With Treatment Emergent Adverse Events (TEAEs) Based on National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 5 | From InO treatment initiation till study completion | An AE was defined as any untoward medical occurrence in a participant temporally associated with the use of study intervention, whether or not considered related to the study intervention. AEs included both serious and all non-serious adverse events. SAE was defined as any untoward medical occurrence that, at any dose resulted in any of the following outcomes: death; life-threatening; required inpatient hospitalization or prolongation of existing hospitalization; persistent or significant disability/incapacity; congenital anomaly/birth defect; or that was considered as an important medical event. According to NCI CTCAE version 5: Grade 1= mild AE; Grade 2= moderate AE; Grade 3=severe AE; Grade 4= life-threatening consequences and urgent intervention indicated; Grade 5= death related to AE. An AE was considered treatment-emergent relative to a given treatment if the event start date is during the on-treatment period (including on the date of first dose). |
| Number of Participants With Treatment Emergent Serious Adverse Events (TESAEs) Based on NCI CTCAE Version 5 | From InO treatment initiation till study completion | An AE was defined as any untoward medical occurrence in a participant temporally associated with the use of study intervention, whether or not considered related to the study intervention. An SAE was defined as any untoward medical occurrence that, at any dose resulted in any of the following outcomes: death; life-threatening; required inpatient hospitalization or prolongation of existing hospitalization; persistent or significant disability/incapacity; congenital anomaly/birth defect; or that was considered as an important medical event. According to NCI CTCAE version 5: Grade 1= mild AE; Grade 2= moderate AE; Grade 3=severe AE; Grade 4= life-threatening consequences and urgent intervention indicated, Grade 5= death related to AE. An AE was considered treatment-emergent relative to a given treatment if the event start date is during the on-treatment period (including on the date of first dose). |
| Number of Participants With TEAEs - Treatment Related Based on NCI CTCAE Version 5 | From InO treatment initiation till study completion | An AE was defined as any untoward medical occurrence in a participant temporally associated with use of study intervention, whether or not considered related to study intervention. AEs included both serious and all non-serious adverse events. SAE was defined as any untoward medical occurrence that, at any dose resulted in any of following outcomes: death; life-threatening; required inpatient hospitalization or prolongation of existing hospitalization; persistent or significant disability/incapacity; congenital anomaly/birth defect; or that was considered as an important medical event. According to NCI CTCAE version 5: Grade 1= mild AE; Grade 2= moderate AE; Grade 3=severe AE; Grade 4= life-threatening consequences and urgent intervention indicated, Grade 5= death related to AE. An AE was considered treatment-emergent relative to a given treatment if event start date is during on-treatment period (including on date of first dose). Relatedness to study drug was assessed by investigator. |
| Duration of Remission (DoR) | From date of first response in responders (CR/CRi) to the date of disease progression (objective progression, relapse from CR/CRi), death due to any cause, whichever occurred first (including post-study treatment follow-up disease assessment) | DoR: from date of first CR/CRi to date of disease progression (objective progression, relapse from CR/CRi), death due to any cause, whichever occurred first. CR: disappearance of leukemia as indicated by \<5% marrow blasts and absence of peripheral blood leukemic blasts, with recovery of hematopoiesis defined by ANC \>=1000 per microliter (/mcL) and platelets \>=10\^5/mcL. C1 EMD status was required (disappearance of all measurable and non-measurable EMD with the exception of lesions for which following must be true: participants with at least 1 measurable lesion, all nodal masses \>1.5 cm in GTD at baseline regressed to \<=1.5 cm in GTD and nodal masses \>=1 cm and \<=1.5 cm in GTD at baseline must have regressed to \<1 cm GTD or reduced by 75% in SPD. No new lesions. Spleen and other previously enlarged organs must have regressed in size and must not be palpable. All diseases must be assessed using same technique as at baseline. CRi: CR except with ANC \<1000/mcL and/or platelets \<10\^5/mcL. |
| Number of Participants With Hematology Laboratory Parameters of Grade <=2 at Baseline to Grade 3 or 4 Post-Baseline | From InO treatment initiation till study completion | Hematology parameters included white blood cell count (with differential including blast count1), hemoglobin and platelet count. Grade 2: moderate; minimal, local or noninvasive intervention indicated; Grade 3: severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self-care; Grade 4: life-threatening consequences. |
| Number of Participants With Hematology Chemistry Parameters of Grade <=2 at Baseline to Grade 3 or 4 Post-Baseline | From InO treatment initiation till study completion | Chemistry parameters included sodium, potassium, magnesium, calcium, creatinine, albumin, alanine aminotransferase, aspartate aminotransferase, glucose, phosphorus, total bilirubin, direct bilirubin only if total is elevated, blood urea nitrogen or urea, uric acid or urate, alkaline phosphatase, lactate dehydrogenase, gamma glutamyl transpeptidase, total protein, amylase and/or lipase. Grade 2: moderate; minimal, local or noninvasive intervention indicated; Grade 3: severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self-care; Grade 4: life-threatening consequences. |
| Number of Participants With Veno-occlusive Disease (VOD) | From InO treatment initiation till study completion | Criteria for VOD were defined as (i) classical VOD (first 21 days after HSCT): bilirubin greater than or equal to 2 mg/dL and two (or more) of the following criteria must also be present; painful hepatomegaly, weight gain \>5%, ascites. (ii) late onset VOD (\>21 days after HSCT): classical VOD beyond day 21 or histologically proven VOD; or two or more of the following criteria must be present: bilirubin \>2 mg/dL; painful hepatomegaly; weight gain \>5%; ascites. |
| Maximum Plasma Concentration (Cmax) of InO on Day 1 of Cycle 1 and Cycle 4 | Cycle 1: Pre-dose (0 hour), 1, 2 and 4 hours post-dose on Day 1; Cycle 4: Pre-dose (0 hour), and 1 hour post-dose on Day 1 | Cmax was defined as maximum observed plasma concentration. Cmax was observed directly from data. |
| Pre-dose Concentration (Ctrough) of InO on Day 1 of Cycle 4 | Pre-dose (0 hour) on Day 1 of Cycle 4 | Ctrough was observed directly from data. |
| Number of Participants With Positive Anti-drug Antibodies (ADA) and Neutralizing Antibodies (NAb) to InO | From InO treatment initiation till study completion | A participant was ADA or NAb positive if (i) baseline titer was missing or negative and participant had \>=1 post treatment positive titer (treatment-induced), or (ii) positive titer at baseline and had a \>=0.602 unit increase in titer (log10) from baseline in \>=1 post-treatment sample (treatment-boosted). |
| Number of Participants With AEs According to Severity Based on NCI CTCAE Version 5 | From InO treatment initiation till study completion | An AE was defined as any untoward medical occurrence in a participant temporally associated with the use of study intervention, whether or not considered related to the study intervention. According to NCI CTCAE version 5: Grade 1= mild AE; Grade 2= moderate AE; Grade 3=severe AE; Grade 4= life-threatening consequences and urgent intervention indicated, Grade 5= death related to AE. |
Countries
China
Participant flow
Recruitment details
A total of 44 participants were assigned to and received study treatment.
Pre-assignment details
Results are reported at Primary Completion Date, and data is disclosed for only those outcome measures whose analysis were final. Remaining outcome measures' data would be reported upon their complete analyses at study completion.
Participants by arm
| Arm | Count |
|---|---|
| Inotuzumab Ozogamicin (InO) Participants received IV infusion of InO as 0.8 mg/m\^2 on Week 1, 0.5 mg/m\^2 on Week2 and 3 every 21-28 days cycle. After Cycle 1: a) participants who achieved desired response, received IV infusion of InO as 0.5 mg/m\^2 on Week 1, Week2 and 3 of subsequent cycles (1 cycle = 28 days); b) participants who did not achieve desired response, received IV infusion of InO as 0.8 mg/m\^2 on Week 1 and 0.5 mg/m\^2 on Week2 and 3 of subsequent cycles (1 cycle = 28 days). Participants who did not achieve desired response within 3 cycles discontinued treatment. Desired response was complete remission or complete remission with incomplete hematologic recovery. | 44 |
| Total | 44 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Follow-Up Phase | Death | 16 |
| Follow-Up Phase | Ongoing | 26 |
| Treatment Phase | Adverse Event | 13 |
| Treatment Phase | Death | 1 |
| Treatment Phase | Physician Decision | 3 |
| Treatment Phase | Progressive disease | 9 |
| Treatment Phase | Withdrawal by Subject | 5 |
Baseline characteristics
| Characteristic | Inotuzumab Ozogamicin (InO) |
|---|---|
| Age, Customized Age 18 to less than 45 years | 22 Participants |
| Age, Customized Age 45 to less than 65 years | 14 Participants |
| Age, Customized Age Greater than or equal to 65 years | 8 Participants |
| Cytogenetics Characteristics Abnormal: DEL(9P) | 2 Participants |
| Cytogenetics Characteristics Abnormal: Other | 16 Participants |
| Cytogenetics Characteristics Abnormal: Ph-positive | 11 Participants |
| Cytogenetics Characteristics Abnormal: T(4;11)-positive | 2 Participants |
| Cytogenetics Characteristics Normal | 20 Participants |
| Cytogenetics Characteristics Unknown | 1 Participants |
| Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) Grade 0 | 10 Participants |
| Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) Grade 1 | 29 Participants |
| Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) Grade 2 | 5 Participants |
| Number of Participants According to Salvage Therapy Salvage Therapy 1 | 23 Participants |
| Number of Participants According to Salvage Therapy Salvage Therapy 2 | 21 Participants |
| Number of Participants With Prior Transplant | 5 Participants |
| Race/Ethnicity, Customized Race - Asian | 44 Participants |
| Racial Designation Han Chinese | 43 Participants |
| Racial Designation Not disclosed | 1 Participants |
| Sex: Female, Male Female | 22 Participants |
| Sex: Female, Male Male | 22 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 17 / 44 |
| other Total, other adverse events | 44 / 44 |
| serious Total, serious adverse events | 20 / 44 |
Outcome results
Primary
Percentage of Participants With Complete Remission (CR) or Complete Remission With Incomplete Hematological Recovery (CRi) as Per Investigator's Assessment According to a Modified Cheson Criteria
CR: disappearance of leukemia as indicated by \<5% marrow blasts and the absence of peripheral blood leukemic blasts, with recovery of hematopoiesis defined by absolute neutrophil count (ANC) \>=1000 per microliter (/mcL) and platelets \>=100,000/mcL. C1 extramedullary disease (EMD) status was required (disappearance of all measurable and non-measurable EMD with the exception of lesions for which following must be true: participants with at least 1 measurable lesion, all nodal masses \>1.5 centimeter (cm) in greatest transverse diameter (GTD) at baseline regressed to \<=1.5 cm in GTD and nodal masses \>=1 cm and \<=1.5 cm in GTD at baseline must have regressed to \<1 cm GTD or reduced by 75% in sum of products of greatest diameters (SPD). No new lesions. Spleen and other previously enlarged organs must have regressed in size and must not be palpable. All diseases were assessed using the same technique as at baseline. CRi: CR except with ANC \<1000/mcL and/or platelets \<100,000/mcL.
Time frame: From InO treatment initiation on Day 1 to CR or CRi (maximum up to 30.1 weeks of treatment exposure)
Population: Safety population included all enrolled participants who received at least 1 dose of study intervention. Data collected after the end of treatment or after new anti-cancer therapy was excluded.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Inotuzumab Ozogamicin (InO) | Percentage of Participants With Complete Remission (CR) or Complete Remission With Incomplete Hematological Recovery (CRi) as Per Investigator's Assessment According to a Modified Cheson Criteria | CR/CRi | 81.8 Percentage of participants |
| Inotuzumab Ozogamicin (InO) | Percentage of Participants With Complete Remission (CR) or Complete Remission With Incomplete Hematological Recovery (CRi) as Per Investigator's Assessment According to a Modified Cheson Criteria | CR | 47.7 Percentage of participants |
| Inotuzumab Ozogamicin (InO) | Percentage of Participants With Complete Remission (CR) or Complete Remission With Incomplete Hematological Recovery (CRi) as Per Investigator's Assessment According to a Modified Cheson Criteria | CRi | 34.1 Percentage of participants |
Secondary
Duration of Remission (DoR)
DoR: from date of first CR/CRi to date of disease progression (objective progression, relapse from CR/CRi), death due to any cause, whichever occurred first. CR: disappearance of leukemia as indicated by \<5% marrow blasts and absence of peripheral blood leukemic blasts, with recovery of hematopoiesis defined by ANC \>=1000 per microliter (/mcL) and platelets \>=10\^5/mcL. C1 EMD status was required (disappearance of all measurable and non-measurable EMD with the exception of lesions for which following must be true: participants with at least 1 measurable lesion, all nodal masses \>1.5 cm in GTD at baseline regressed to \<=1.5 cm in GTD and nodal masses \>=1 cm and \<=1.5 cm in GTD at baseline must have regressed to \<1 cm GTD or reduced by 75% in SPD. No new lesions. Spleen and other previously enlarged organs must have regressed in size and must not be palpable. All diseases must be assessed using same technique as at baseline. CRi: CR except with ANC \<1000/mcL and/or platelets \<10\^5/mcL.
Time frame: From date of first response in responders (CR/CRi) to the date of disease progression (objective progression, relapse from CR/CRi), death due to any cause, whichever occurred first (including post-study treatment follow-up disease assessment)
Population: Safety population included all enrolled participants who received at least 1 dose of study intervention.
Secondary
Maximum Plasma Concentration (Cmax) of InO on Day 1 of Cycle 1 and Cycle 4
Cmax was defined as maximum observed plasma concentration. Cmax was observed directly from data.
Time frame: Cycle 1: Pre-dose (0 hour), 1, 2 and 4 hours post-dose on Day 1; Cycle 4: Pre-dose (0 hour), and 1 hour post-dose on Day 1
Population: Pharmacokinetic (PK) concentration population included subset of the safety analysis set and included participants who had at least one post-dose concentration measurement above the lower limit of quantitation (LLQ) for inotuzumab ozogamicin. Here, 'Number Analyzed' signifies participants evaluable at specific timepoints.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Inotuzumab Ozogamicin (InO) | Maximum Plasma Concentration (Cmax) of InO on Day 1 of Cycle 1 and Cycle 4 | Day 1_Cycle 1 | 273.3 Nanogram per milliliter | Standard Deviation 105.53 |
| Inotuzumab Ozogamicin (InO) | Maximum Plasma Concentration (Cmax) of InO on Day 1 of Cycle 1 and Cycle 4 | Day 1_Cycle 4 | 342.6 Nanogram per milliliter | Standard Deviation 409.97 |
Secondary
Number of Participants Who Proceeded to Hematopoietic Stem Cell Transplantation (HSCT)
Participants who proceeded to HSCT was reported. HSCT is a procedure where multipotent hematopoietic stem cells are transplanted from sources such as bone marrow, peripheral blood, or umbilical cord blood. These stem cells can replicate inside a participant and produce additional normal blood cells.
Time frame: From InO treatment initiation till study completion
Population: Safety population included all enrolled participants who received at least 1 dose of study intervention.
Secondary
Number of Participants With AEs According to Severity Based on NCI CTCAE Version 5
An AE was defined as any untoward medical occurrence in a participant temporally associated with the use of study intervention, whether or not considered related to the study intervention. According to NCI CTCAE version 5: Grade 1= mild AE; Grade 2= moderate AE; Grade 3=severe AE; Grade 4= life-threatening consequences and urgent intervention indicated, Grade 5= death related to AE.
Time frame: From InO treatment initiation till study completion
Population: Safety population included all enrolled participants who received at least 1 dose of study intervention.
Secondary
Number of Participants With Hematology Chemistry Parameters of Grade <=2 at Baseline to Grade 3 or 4 Post-Baseline
Chemistry parameters included sodium, potassium, magnesium, calcium, creatinine, albumin, alanine aminotransferase, aspartate aminotransferase, glucose, phosphorus, total bilirubin, direct bilirubin only if total is elevated, blood urea nitrogen or urea, uric acid or urate, alkaline phosphatase, lactate dehydrogenase, gamma glutamyl transpeptidase, total protein, amylase and/or lipase. Grade 2: moderate; minimal, local or noninvasive intervention indicated; Grade 3: severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self-care; Grade 4: life-threatening consequences.
Time frame: From InO treatment initiation till study completion
Population: Safety population included all enrolled participants who received at least 1 dose of study intervention.
Secondary
Number of Participants With Hematology Laboratory Parameters of Grade <=2 at Baseline to Grade 3 or 4 Post-Baseline
Hematology parameters included white blood cell count (with differential including blast count1), hemoglobin and platelet count. Grade 2: moderate; minimal, local or noninvasive intervention indicated; Grade 3: severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self-care; Grade 4: life-threatening consequences.
Time frame: From InO treatment initiation till study completion
Population: Safety population included all enrolled participants who received at least 1 dose of study intervention.
Secondary
Number of Participants With Positive Anti-drug Antibodies (ADA) and Neutralizing Antibodies (NAb) to InO
A participant was ADA or NAb positive if (i) baseline titer was missing or negative and participant had \>=1 post treatment positive titer (treatment-induced), or (ii) positive titer at baseline and had a \>=0.602 unit increase in titer (log10) from baseline in \>=1 post-treatment sample (treatment-boosted).
Time frame: From InO treatment initiation till study completion
Population: Immunogenicity population included subset of the safety analysis set and included participants who received at least 1 dose of investigational product (inotuzumab ozogamicin) and had at least one ADA or NAb sample collected for immunogenicity.
Secondary
Number of Participants With TEAEs - Treatment Related Based on NCI CTCAE Version 5
An AE was defined as any untoward medical occurrence in a participant temporally associated with use of study intervention, whether or not considered related to study intervention. AEs included both serious and all non-serious adverse events. SAE was defined as any untoward medical occurrence that, at any dose resulted in any of following outcomes: death; life-threatening; required inpatient hospitalization or prolongation of existing hospitalization; persistent or significant disability/incapacity; congenital anomaly/birth defect; or that was considered as an important medical event. According to NCI CTCAE version 5: Grade 1= mild AE; Grade 2= moderate AE; Grade 3=severe AE; Grade 4= life-threatening consequences and urgent intervention indicated, Grade 5= death related to AE. An AE was considered treatment-emergent relative to a given treatment if event start date is during on-treatment period (including on date of first dose). Relatedness to study drug was assessed by investigator.
Time frame: From InO treatment initiation till study completion
Population: Safety population included all enrolled participants who received at least 1 dose of study intervention.
Secondary
Number of Participants With Treatment Emergent Adverse Events (TEAEs) Based on National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 5
An AE was defined as any untoward medical occurrence in a participant temporally associated with the use of study intervention, whether or not considered related to the study intervention. AEs included both serious and all non-serious adverse events. SAE was defined as any untoward medical occurrence that, at any dose resulted in any of the following outcomes: death; life-threatening; required inpatient hospitalization or prolongation of existing hospitalization; persistent or significant disability/incapacity; congenital anomaly/birth defect; or that was considered as an important medical event. According to NCI CTCAE version 5: Grade 1= mild AE; Grade 2= moderate AE; Grade 3=severe AE; Grade 4= life-threatening consequences and urgent intervention indicated; Grade 5= death related to AE. An AE was considered treatment-emergent relative to a given treatment if the event start date is during the on-treatment period (including on the date of first dose).
Time frame: From InO treatment initiation till study completion
Population: Safety population included all enrolled participants who received at least 1 dose of study intervention.
Secondary
Number of Participants With Treatment Emergent Serious Adverse Events (TESAEs) Based on NCI CTCAE Version 5
An AE was defined as any untoward medical occurrence in a participant temporally associated with the use of study intervention, whether or not considered related to the study intervention. An SAE was defined as any untoward medical occurrence that, at any dose resulted in any of the following outcomes: death; life-threatening; required inpatient hospitalization or prolongation of existing hospitalization; persistent or significant disability/incapacity; congenital anomaly/birth defect; or that was considered as an important medical event. According to NCI CTCAE version 5: Grade 1= mild AE; Grade 2= moderate AE; Grade 3=severe AE; Grade 4= life-threatening consequences and urgent intervention indicated, Grade 5= death related to AE. An AE was considered treatment-emergent relative to a given treatment if the event start date is during the on-treatment period (including on the date of first dose).
Time frame: From InO treatment initiation till study completion
Population: Safety population included all enrolled participants who received at least 1 dose of study intervention.
Secondary
Number of Participants With Veno-occlusive Disease (VOD)
Criteria for VOD were defined as (i) classical VOD (first 21 days after HSCT): bilirubin greater than or equal to 2 mg/dL and two (or more) of the following criteria must also be present; painful hepatomegaly, weight gain \>5%, ascites. (ii) late onset VOD (\>21 days after HSCT): classical VOD beyond day 21 or histologically proven VOD; or two or more of the following criteria must be present: bilirubin \>2 mg/dL; painful hepatomegaly; weight gain \>5%; ascites.
Time frame: From InO treatment initiation till study completion
Population: Safety population included all enrolled participants who received at least 1 dose of study intervention.
Secondary
Overall Survival (OS)
OS was defined as the time from date of first dose to the date of death due to any cause. Participants without confirmation of death were to be censored on date of last contact.
Time frame: From date of first dose to the date of death due to any cause or censoring, whichever occurred first
Population: Safety population included all enrolled participants who received at least 1 dose of study intervention.
Secondary
Percentage of Participants With Minimal Residual Disease (MRD) Negativity Among Who Achieved CR/CRi
MRD negativity was defined as malignant B lymphocytes occurring at frequency \<10\^4. CR: disappearance of leukemia as indicated by \<5% marrow blasts and absence of peripheral blood leukemic blasts, with recovery of hematopoiesis defined by ANC \>=1000 per microliter (/mcL) and platelets \>=10\^5/mcL. C1 EMD status was required (disappearance of all measurable and non-measurable EMD with the exception of lesions for which following must be true: participants with at least 1 measurable lesion, all nodal masses \>1.5 cm in GTD at baseline regressed to \<=1.5 cm in GTD and nodal masses \>=1 cm and \<=1.5 cm in GTD at baseline must have regressed to \<1 cm GTD or reduced by 75% in SPD. No new lesions. Spleen and other previously enlarged organs must have regressed in size and must not be palpable. All diseases must be assessed using same technique as at baseline. CRi: CR except with ANC \<1000/mcL and/or platelets \<10\^5/mcL.
Time frame: From CR/CRi till MRD negativity achieved (maximum up to 30.1 weeks of treatment exposure)
Population: Safety population included all enrolled participants who received at least 1 dose of study intervention. Here, Overall Number of Participants Analyzed signifies participants who achieved CR/CRi and were evaluated for this outcome measure.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Inotuzumab Ozogamicin (InO) | Percentage of Participants With Minimal Residual Disease (MRD) Negativity Among Who Achieved CR/CRi | 69.4 Percentage of participants |
Secondary
Pre-dose Concentration (Ctrough) of InO on Day 1 of Cycle 4
Ctrough was observed directly from data.
Time frame: Pre-dose (0 hour) on Day 1 of Cycle 4
Population: PK concentration population included subset of the safety analysis set and included participants who had at least one post-dose concentration measurement above the LLQ for inotuzumab ozogamicin. Here, 'Overall Number of Participants Analyzed' signifies participants evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Inotuzumab Ozogamicin (InO) | Pre-dose Concentration (Ctrough) of InO on Day 1 of Cycle 4 | 85.33 Nanogram per milliliter | Standard Deviation 30.493 |
Secondary
Progression-free Survival (PFS)
PFS: from date of first dose to date of disease progression (objective progression, relapse from CR/CRi), or death due to any cause, whichever occurred first. CR: disappearance of leukemia as indicated by \<5% marrow blasts and absence of peripheral blood leukemic blasts, with recovery of hematopoiesis defined by ANC \>=1000 per microliter (/mcL) and platelets \>=10\^5/mcL. C1 EMD status was required (disappearance of all measurable and non-measurable EMD with the exception of lesions for which following must be true: participants with at least 1 measurable lesion, all nodal masses \>1.5 cm in GTD at baseline regressed to \<=1.5 cm in GTD and nodal masses \>=1 cm and \<=1.5 cm in GTD at baseline must have regressed to \<1 cm GTD or reduced by 75% in SPD. No new lesions. Spleen and other previously enlarged organs must have regressed in size and must not be palpable. All diseases must be assessed using same technique as at baseline. CRi: CR except with ANC \<1000/mcL and/or platelets \<10\^5/mcL.
Time frame: From date of first dose to the date of disease progression (objective progression, relapse from CR/CRi), or death due to any cause, whichever occurred first
Population: Safety population included all enrolled participants who received at least 1 dose of study intervention.