Trial Outcomes & Findings for A Study Of Two Inotuzumab Ozogamicin Doses in Relapsed/ Refractory Acute Lymphoblastic Leukemia Transplant Eligible Patients (NCT NCT03677596)

Last Updated: 2023-11-22

Results Overview

VOD happened when the small blood vessels that lead into the liver and were inside the liver become blocked. VOD is defined as: a. Classical VOD (first 21 days after HSCT): Bilirubin\>=2 mg/dL and 2 (or more) of the following criteria must also be present: 1. Painful hepatomegaly; 2. Weight gain \>5%; 3. Ascites. b. 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: 1. Bilirubin \>2 mg/dL; 2. Painful hepatomegaly; 3. Weight gain \>5%; 4. Ascites. and hemodynamical and/or ultrasound evidence of VOD.

Recruitment status

COMPLETED

Study phase

PHASE4

Target enrollment

102 participants

Primary outcome timeframe

2 years from randomization

Results posted on

2023-11-22

Participant Flow

A total of 102 were enrolled. In Run-in Phase, 22 participants were enrolled and treated. In Randomized Phase, 80 participants were enrolled and treated.

Participant milestones

Participant milestones
Measure	1.2 mg/m²/Cycle (Dose Level 2 Run-in + Randomized) Participants received a starting dose of inotuzumab ozogamicin 1.2 mg/m²/cycle (0.6 mg/m² on Day 1, 0.3 mg/m² on Days 8 and 15) intravenously. After complete remission (CR)/complete remission with incomplete hematologic recovery (CRi) is achieved, the dose was reduced to 0.9 mg/m²/cycle (0.3 mg/m² on Day 1, 8 and 15). The maximum treatment duration was approximately 52 weeks.	1.8 mg/m²/Cycle (Dose Level 1 Randomized Phase) Participants received a starting dose of inotuzumab ozogamicin 1.8 mg/m²/cycle administrated in 3 divided doses (0.8 mg/m² on Day 1, 0.5 mg/m² on Days 8 and 15) intravenously. After CR/CRi was achieved, the dose was reduced to 1.5 mg/m²/cycle (0.5 mg/m² on Days 1, 8 and 15) for 2-3 cycles. The cycle length was 21-28 days. The maximum treatment duration was approximately 52 weeks.
Overall Study STARTED	64	38
Overall Study COMPLETED	41	19
Overall Study NOT COMPLETED	23	19

Reasons for withdrawal

Reasons for withdrawal
Measure	1.2 mg/m²/Cycle (Dose Level 2 Run-in + Randomized) Participants received a starting dose of inotuzumab ozogamicin 1.2 mg/m²/cycle (0.6 mg/m² on Day 1, 0.3 mg/m² on Days 8 and 15) intravenously. After complete remission (CR)/complete remission with incomplete hematologic recovery (CRi) is achieved, the dose was reduced to 0.9 mg/m²/cycle (0.3 mg/m² on Day 1, 8 and 15). The maximum treatment duration was approximately 52 weeks.	1.8 mg/m²/Cycle (Dose Level 1 Randomized Phase) Participants received a starting dose of inotuzumab ozogamicin 1.8 mg/m²/cycle administrated in 3 divided doses (0.8 mg/m² on Day 1, 0.5 mg/m² on Days 8 and 15) intravenously. After CR/CRi was achieved, the dose was reduced to 1.5 mg/m²/cycle (0.5 mg/m² on Days 1, 8 and 15) for 2-3 cycles. The cycle length was 21-28 days. The maximum treatment duration was approximately 52 weeks.
Overall Study Adverse Event	0	1
Overall Study Death	10	6
Overall Study Lost to Follow-up	0	1
Overall Study Progressive Disease	8	8
Overall Study Withdrawal by Subject	3	0
Overall Study Disease Relapse	2	2
Overall Study Other	0	1

Baseline Characteristics

A Study Of Two Inotuzumab Ozogamicin Doses in Relapsed/ Refractory Acute Lymphoblastic Leukemia Transplant Eligible Patients

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	1.2 mg/m²/Cycle (Dose Level 2 Run-in) n=22 Participants Participants received a starting dose of inotuzumab ozogamicin 1.2 mg/m²/cycle administrated in 3 divided doses (0.6 mg/m² on Day1, 0.3 mg/m² on Days 8 and 15) intravenously. After complete response (CR)/complete remission with incomplete hematologic recovery (CRi) was achieved, the dose was reduced to 0.9 mg/m²/cycle (0.3 mg/m² on Days 1, 8 and 15). The cycle length was 21-28 days. The maximum treatment duration was approximately 52 weeks.	1.2 mg/m²/Cycle (Dose Level 2 Randomized Phase) n=42 Participants Participants received a starting dose of inotuzumab ozogamicin 1.2 mg/m²/cycle administrated in 3 divided doses (0.6 mg/m² on Day 1, 0.3 mg/m² on Days 8 and 15) intravenously. After CR/CRi was achieved, the dose was reduced to 0.9 mg/m²/cycle (0.3 mg/m² on Days 1, 8 and 15) for 2-3 cycles. The cycle length was 21-28 days. The maximum treatment duration was approximately 52 weeks.	1.8 mg/m²/Cycle (Dose Level 1 Randomized Phase) n=38 Participants Participants received a starting dose of inotuzumab ozogamicin 1.8 mg/m²/cycle administrated in 3 divided doses (0.8 mg/m² on Day 1, 0.5 mg/m² on Days 8 and 15) intravenously. After CR/CRi was achieved, the dose was reduced to 1.5 mg/m²/cycle (0.5 mg/m² on Days 1, 8 and 15) for 2-3 cycles. The cycle length was 21-28 days. The maximum treatment duration was approximately 52 weeks.	Total n=102 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants	0 Participants n=483 Participants
Age, Categorical Between 18 and 65 years	21 Participants n=93 Participants	38 Participants n=4 Participants	36 Participants n=27 Participants	95 Participants n=483 Participants
Age, Categorical >=65 years	1 Participants n=93 Participants	4 Participants n=4 Participants	2 Participants n=27 Participants	7 Participants n=483 Participants
Sex: Female, Male Female	10 Participants n=93 Participants	18 Participants n=4 Participants	18 Participants n=27 Participants	46 Participants n=483 Participants
Sex: Female, Male Male	12 Participants n=93 Participants	24 Participants n=4 Participants	20 Participants n=27 Participants	56 Participants n=483 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	2 Participants n=93 Participants	5 Participants n=4 Participants	3 Participants n=27 Participants	10 Participants n=483 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	20 Participants n=93 Participants	36 Participants n=4 Participants	35 Participants n=27 Participants	91 Participants n=483 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=93 Participants	1 Participants n=4 Participants	0 Participants n=27 Participants	1 Participants n=483 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants	0 Participants n=483 Participants
Race (NIH/OMB) Asian	5 Participants n=93 Participants	6 Participants n=4 Participants	11 Participants n=27 Participants	22 Participants n=483 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants	0 Participants n=483 Participants
Race (NIH/OMB) Black or African American	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants	0 Participants n=483 Participants
Race (NIH/OMB) White	17 Participants n=93 Participants	34 Participants n=4 Participants	25 Participants n=27 Participants	76 Participants n=483 Participants
Race (NIH/OMB) More than one race	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants	0 Participants n=483 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=93 Participants	2 Participants n=4 Participants	2 Participants n=27 Participants	4 Participants n=483 Participants
ECOG Performance Status ECOG = 0	9 Participants n=93 Participants	19 Participants n=4 Participants	20 Participants n=27 Participants	48 Participants n=483 Participants
ECOG Performance Status ECOG = 1	13 Participants n=93 Participants	20 Participants n=4 Participants	13 Participants n=27 Participants	46 Participants n=483 Participants
ECOG Performance Status ECOG = 2	0 Participants n=93 Participants	3 Participants n=4 Participants	5 Participants n=27 Participants	8 Participants n=483 Participants
Body Mass Index (BMI)	24.98 kg/m^2 n=93 Participants	25.31 kg/m^2 n=4 Participants	24.78 kg/m^2 n=27 Participants	25.26 kg/m^2 n=483 Participants
Body Surface Area (BSA)	1.86 m^2 n=93 Participants	1.82 m^2 n=4 Participants	1.79 m^2 n=27 Participants	1.80 m^2 n=483 Participants

PRIMARY outcome

Timeframe: 2 years from randomization

Population: All randomized participants who received at least 1 dose of study drug.

Outcome measures

Outcome measures
Measure	1.2 mg/m²/Cycle (Dose Level 2 Run-in) n=22 Participants Participants received a starting dose of inotuzumab ozogamicin 1.2 mg/m²/cycle administrated in 3 divided doses (0.6 mg/m² on Day1, 0.3 mg/m² on Days 8 and 15) intravenously. After complete response (CR)/complete remission with incomplete hematologic recovery (CRi) was achieved, the dose was reduced to 0.9 mg/m²/cycle (0.3 mg/m² on Days 1, 8 and 15). The cycle length was 21-28 days. The maximum treatment duration was approximately 52 weeks.	1.2 mg/m²/Cycle (Dose Level 2 Randomized) n=42 Participants Participants received a starting dose of inotuzumab ozogamicin 1.2 mg/m²/cycle (0.6 mg/m² on Day 1, 0.3 mg/m² on Day 8 and 15) intravenously. After CR/CRi is achieved, the dose was reduced to 0.9 mg/m²/cycle (0.3 mg/m² on Day 1, 8 and 15) for 2-3 cycles. The cycle length was 21-28 days. The maximum treatment duration was approximately 52 weeks.	1.2 mg/m²/Cycle (Dose Level 2 Run-in + Randomized) n=64 Participants Participants received a starting dose of inotuzumab ozogamicin 1.2 mg/m²/cycle (0.6 mg/m² on Day 1, 0.3 mg/m² on Days 8 and 15) intravenously. After complete remission (CR)/complete remission with incomplete hematologic recovery (CRi) is achieved, the dose was reduced to 0.9 mg/m²/cycle (0.3 mg/m² on Day 1, 8 and 15). The maximum treatment duration was approximately 52 weeks.	1.8 mg/m²/Cycle (Dose Level 1 Randomized) n=38 Participants Participants received a starting dose of inotuzumab ozogamicin 1.8 mg/m²/cycle (0.8 mg/m² on Day 1, 0.5 mg/m² on Day 8 and 15) intravenously. After CR/CRi is achieved, the dose was reduced to 1.5 mg/m²/cycle (0.5 mg/m² on Day 1, 8 and 15) for 2-3 cycles. The cycle length was 21-28 days. The maximum treatment duration was approximately 52 weeks.
Percentage of Participants With Veno-occlusive Disease (VOD)	9.1 Percentage of Participants	14.3 Percentage of Participants	12.5 Percentage of Participants	5.3 Percentage of Participants

PRIMARY outcome

Timeframe: From first dose of study treatment of 6 cycles till follow-up up to 2 years, in total approximately 2.5 years

Population: All participants who were randomized into the study with study drug assignment based on randomization.

CR is defined as a 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/µL and platelets\>=100000/µL. C1 extramedullary disease status is required. CRi is defined as CR except with ANC \<1000/µL and/or platelets \<100000/µL. C1 defined as complete disappearance of all measurable and non-measurable extramedullary disease with the exception of lesions with following must be true: For participants with\>= 1 measurable lesion, all nodal masses\>1.5cm in greatest transverse diameter (GTD) at baseline (last assessment before 1st dose of study treatment) must must have regressed to\>=1.5cm in GTD and all nodal masses\>=1cm \& \<=1.5cm in GTD at baseline have regressed to \<1cm GTD or must have reduced by 75% in sum of products of greatest diameters. No new lesions. Spleen and other previously enlarged organs must have regressed in size and must not be palpable.

Outcome measures

Outcome measures
Measure	1.2 mg/m²/Cycle (Dose Level 2 Run-in) n=22 Participants Participants received a starting dose of inotuzumab ozogamicin 1.2 mg/m²/cycle administrated in 3 divided doses (0.6 mg/m² on Day1, 0.3 mg/m² on Days 8 and 15) intravenously. After complete response (CR)/complete remission with incomplete hematologic recovery (CRi) was achieved, the dose was reduced to 0.9 mg/m²/cycle (0.3 mg/m² on Days 1, 8 and 15). The cycle length was 21-28 days. The maximum treatment duration was approximately 52 weeks.	1.2 mg/m²/Cycle (Dose Level 2 Randomized) n=42 Participants Participants received a starting dose of inotuzumab ozogamicin 1.2 mg/m²/cycle (0.6 mg/m² on Day 1, 0.3 mg/m² on Day 8 and 15) intravenously. After CR/CRi is achieved, the dose was reduced to 0.9 mg/m²/cycle (0.3 mg/m² on Day 1, 8 and 15) for 2-3 cycles. The cycle length was 21-28 days. The maximum treatment duration was approximately 52 weeks.	1.2 mg/m²/Cycle (Dose Level 2 Run-in + Randomized) n=64 Participants Participants received a starting dose of inotuzumab ozogamicin 1.2 mg/m²/cycle (0.6 mg/m² on Day 1, 0.3 mg/m² on Days 8 and 15) intravenously. After complete remission (CR)/complete remission with incomplete hematologic recovery (CRi) is achieved, the dose was reduced to 0.9 mg/m²/cycle (0.3 mg/m² on Day 1, 8 and 15). The maximum treatment duration was approximately 52 weeks.	1.8 mg/m²/Cycle (Dose Level 1 Randomized) n=38 Participants Participants received a starting dose of inotuzumab ozogamicin 1.8 mg/m²/cycle (0.8 mg/m² on Day 1, 0.5 mg/m² on Day 8 and 15) intravenously. After CR/CRi is achieved, the dose was reduced to 1.5 mg/m²/cycle (0.5 mg/m² on Day 1, 8 and 15) for 2-3 cycles. The cycle length was 21-28 days. The maximum treatment duration was approximately 52 weeks.
Rate of Hematologic Remission (Complete Response [CR] / Complete Response With Incomplete Hematologic Recovery[CRi])	50.0 Percentage of Participants	83.3 Percentage of Participants	71.9 Percentage of Participants	68.4 Percentage of Participants

SECONDARY outcome

Timeframe: From first dose of study treatment drug through 63 days after last dose (approximately 52 weeks)

Population: All randomized participants who receive at least 1 dose of study drug.

Adverse event (AE) = any untoward medical occurrence in participant who received study treatment without regard to possibility of causal relationship. On-treatment period was defined as the period starting with the 1st dose of study treatment through 63 days after last dose or 1 day before start day of new anticancer therapy, whichever occurred first. A serious adverse event (SAE) was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. All VOD cases were reported as SAE. Grades of severity were defined by Common terminology criteria for adverse events (CTCAE) v3.0. Grade 3=severe adverse event; Grade 4=life-threatening consequences; urgent intervention indicated. Grade 5=death related to AE. Results were reported as of the data cutoff date on 21 Sep 2022.

Outcome measures

Outcome measures
Measure	1.2 mg/m²/Cycle (Dose Level 2 Run-in) n=22 Participants Participants received a starting dose of inotuzumab ozogamicin 1.2 mg/m²/cycle administrated in 3 divided doses (0.6 mg/m² on Day1, 0.3 mg/m² on Days 8 and 15) intravenously. After complete response (CR)/complete remission with incomplete hematologic recovery (CRi) was achieved, the dose was reduced to 0.9 mg/m²/cycle (0.3 mg/m² on Days 1, 8 and 15). The cycle length was 21-28 days. The maximum treatment duration was approximately 52 weeks.	1.2 mg/m²/Cycle (Dose Level 2 Randomized) n=42 Participants Participants received a starting dose of inotuzumab ozogamicin 1.2 mg/m²/cycle (0.6 mg/m² on Day 1, 0.3 mg/m² on Day 8 and 15) intravenously. After CR/CRi is achieved, the dose was reduced to 0.9 mg/m²/cycle (0.3 mg/m² on Day 1, 8 and 15) for 2-3 cycles. The cycle length was 21-28 days. The maximum treatment duration was approximately 52 weeks.	1.2 mg/m²/Cycle (Dose Level 2 Run-in + Randomized) n=64 Participants Participants received a starting dose of inotuzumab ozogamicin 1.2 mg/m²/cycle (0.6 mg/m² on Day 1, 0.3 mg/m² on Days 8 and 15) intravenously. After complete remission (CR)/complete remission with incomplete hematologic recovery (CRi) is achieved, the dose was reduced to 0.9 mg/m²/cycle (0.3 mg/m² on Day 1, 8 and 15). The maximum treatment duration was approximately 52 weeks.	1.8 mg/m²/Cycle (Dose Level 1 Randomized) n=38 Participants Participants received a starting dose of inotuzumab ozogamicin 1.8 mg/m²/cycle (0.8 mg/m² on Day 1, 0.5 mg/m² on Day 8 and 15) intravenously. After CR/CRi is achieved, the dose was reduced to 1.5 mg/m²/cycle (0.5 mg/m² on Day 1, 8 and 15) for 2-3 cycles. The cycle length was 21-28 days. The maximum treatment duration was approximately 52 weeks.
Number of Participants With Treatment-Emergent Adverse Events (All Causalities) Participants with adverse events	22 Participants	42 Participants	64 Participants	38 Participants
Number of Participants With Treatment-Emergent Adverse Events (All Causalities) Participants with SAEs	15 Participants	28 Participants	43 Participants	21 Participants
Number of Participants With Treatment-Emergent Adverse Events (All Causalities) Participants with Maximum Grade 3 or 4 adverse events	9 Participants	22 Participants	31 Participants	18 Participants
Number of Participants With Treatment-Emergent Adverse Events (All Causalities) Participants with Maximum Grade 5 adverse events	7 Participants	11 Participants	18 Participants	10 Participants

SECONDARY outcome

Timeframe: From first dose of study treatment drug through 63 days after last dose (approximately 52 weeks)

Population: All randomized participants who receive at least 1 dose of study drug.

Adverse event (AE) = any untoward medical occurrence in participant who received study treatment without regard to possibility of causal relationship. Treatment emergent AEs (TEAEs) were defined as AEs that reported the period starting with the first dose of study treatment drug through 63 days after last dose or 1 day before start day of new anticancer therapy, whichever occurred first. A SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Grades of severity were defined by CTCAE v3.0. Grade 3 = severe adverse event; Grade 4 = life-threatening consequences; urgent intervention indicated. Grade 5 = death related to AE. Causality of TEAEs were assessed by the Investigator. Results were reported as of the data cutoff date on 21 Sep 2022.

Outcome measures

Outcome measures
Measure	1.2 mg/m²/Cycle (Dose Level 2 Run-in) n=22 Participants Participants received a starting dose of inotuzumab ozogamicin 1.2 mg/m²/cycle administrated in 3 divided doses (0.6 mg/m² on Day1, 0.3 mg/m² on Days 8 and 15) intravenously. After complete response (CR)/complete remission with incomplete hematologic recovery (CRi) was achieved, the dose was reduced to 0.9 mg/m²/cycle (0.3 mg/m² on Days 1, 8 and 15). The cycle length was 21-28 days. The maximum treatment duration was approximately 52 weeks.	1.2 mg/m²/Cycle (Dose Level 2 Randomized) n=42 Participants Participants received a starting dose of inotuzumab ozogamicin 1.2 mg/m²/cycle (0.6 mg/m² on Day 1, 0.3 mg/m² on Day 8 and 15) intravenously. After CR/CRi is achieved, the dose was reduced to 0.9 mg/m²/cycle (0.3 mg/m² on Day 1, 8 and 15) for 2-3 cycles. The cycle length was 21-28 days. The maximum treatment duration was approximately 52 weeks.	1.2 mg/m²/Cycle (Dose Level 2 Run-in + Randomized) n=64 Participants Participants received a starting dose of inotuzumab ozogamicin 1.2 mg/m²/cycle (0.6 mg/m² on Day 1, 0.3 mg/m² on Days 8 and 15) intravenously. After complete remission (CR)/complete remission with incomplete hematologic recovery (CRi) is achieved, the dose was reduced to 0.9 mg/m²/cycle (0.3 mg/m² on Day 1, 8 and 15). The maximum treatment duration was approximately 52 weeks.	1.8 mg/m²/Cycle (Dose Level 1 Randomized) n=38 Participants Participants received a starting dose of inotuzumab ozogamicin 1.8 mg/m²/cycle (0.8 mg/m² on Day 1, 0.5 mg/m² on Day 8 and 15) intravenously. After CR/CRi is achieved, the dose was reduced to 1.5 mg/m²/cycle (0.5 mg/m² on Day 1, 8 and 15) for 2-3 cycles. The cycle length was 21-28 days. The maximum treatment duration was approximately 52 weeks.
Number of Participants With Treatment-Emergent Adverse Events (Treatment-related) Participants with AEs	13 Participants	18 Participants	31 Participants	22 Participants
Number of Participants With Treatment-Emergent Adverse Events (Treatment-related) Participants with SAEs	7 Participants	8 Participants	15 Participants	10 Participants
Number of Participants With Treatment-Emergent Adverse Events (Treatment-related) Participants with Maximum Grade 3 or 4 AEs	9 Participants	11 Participants	20 Participants	11 Participants
Number of Participants With Treatment-Emergent Adverse Events (Treatment-related) Participants with Maximum Grade 5 AEs	1 Participants	1 Participants	2 Participants	4 Participants

SECONDARY outcome

Timeframe: Starting from the first transplant after inotuzumab ozogamicin treatment and including the entire duration of subsequent follow up (approximately 52 weeks))

Population: All randomized participants who receive at least 1 dose of study drug and were post HSCT.

A serious adverse event (SAE) was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. All SAEs occurred after HSCT were reported in this OM. Results were reported as of the data cutoff date on 21 Sep 2022.

Outcome measures

Outcome measures
Measure	1.2 mg/m²/Cycle (Dose Level 2 Run-in) n=10 Participants Participants received a starting dose of inotuzumab ozogamicin 1.2 mg/m²/cycle administrated in 3 divided doses (0.6 mg/m² on Day1, 0.3 mg/m² on Days 8 and 15) intravenously. After complete response (CR)/complete remission with incomplete hematologic recovery (CRi) was achieved, the dose was reduced to 0.9 mg/m²/cycle (0.3 mg/m² on Days 1, 8 and 15). The cycle length was 21-28 days. The maximum treatment duration was approximately 52 weeks.	1.2 mg/m²/Cycle (Dose Level 2 Randomized) n=21 Participants Participants received a starting dose of inotuzumab ozogamicin 1.2 mg/m²/cycle (0.6 mg/m² on Day 1, 0.3 mg/m² on Day 8 and 15) intravenously. After CR/CRi is achieved, the dose was reduced to 0.9 mg/m²/cycle (0.3 mg/m² on Day 1, 8 and 15) for 2-3 cycles. The cycle length was 21-28 days. The maximum treatment duration was approximately 52 weeks.	1.2 mg/m²/Cycle (Dose Level 2 Run-in + Randomized) n=31 Participants Participants received a starting dose of inotuzumab ozogamicin 1.2 mg/m²/cycle (0.6 mg/m² on Day 1, 0.3 mg/m² on Days 8 and 15) intravenously. After complete remission (CR)/complete remission with incomplete hematologic recovery (CRi) is achieved, the dose was reduced to 0.9 mg/m²/cycle (0.3 mg/m² on Day 1, 8 and 15). The maximum treatment duration was approximately 52 weeks.	1.8 mg/m²/Cycle (Dose Level 1 Randomized) n=12 Participants Participants received a starting dose of inotuzumab ozogamicin 1.8 mg/m²/cycle (0.8 mg/m² on Day 1, 0.5 mg/m² on Day 8 and 15) intravenously. After CR/CRi is achieved, the dose was reduced to 1.5 mg/m²/cycle (0.5 mg/m² on Day 1, 8 and 15) for 2-3 cycles. The cycle length was 21-28 days. The maximum treatment duration was approximately 52 weeks.
Number of Participants With Treatment-Emergent Serious Adverse Events (Post-HSCT)	6 Participants	8 Participants	14 Participants	2 Participants

SECONDARY outcome

Timeframe: From first dose of study treatment drug through 63 days after last dose (approximately 52 weeks)

Population: All randomized participants who receive at least 1 dose of study drug and with at least 1 postbaseline assessment in each treatment group. 'Number analyzed' = Participants evaluable for this outcome measure for each specified row.

Baseline assessment was defined as the last assessment performed on or prior to the date of the first dose of study treatment. Following Parameters were analyzed for laboratory assessment: Hematology (Activated partial thromboplastin time prolonged, Anemia, Hemoglobin increased, International normalization rate (INR) increased, Leukocytosis, Lymphocyte count decreased, Lymphocyte count increased, Neutrophil count decreased, Platelet count decreased, White blood cell decreased). Grades of severity were defined by CTCAE v3.0. Grade 2 = moderate adverse event; Grade 3= severe adverse event; Grade 4 = life-threatening consequences; urgent intervention indicated. Results were reported as of the data cutoff date on 21 Sep 2022.

Outcome measures

Outcome measures
Measure	1.2 mg/m²/Cycle (Dose Level 2 Run-in) n=22 Participants Participants received a starting dose of inotuzumab ozogamicin 1.2 mg/m²/cycle administrated in 3 divided doses (0.6 mg/m² on Day1, 0.3 mg/m² on Days 8 and 15) intravenously. After complete response (CR)/complete remission with incomplete hematologic recovery (CRi) was achieved, the dose was reduced to 0.9 mg/m²/cycle (0.3 mg/m² on Days 1, 8 and 15). The cycle length was 21-28 days. The maximum treatment duration was approximately 52 weeks.	1.2 mg/m²/Cycle (Dose Level 2 Randomized) n=42 Participants Participants received a starting dose of inotuzumab ozogamicin 1.2 mg/m²/cycle (0.6 mg/m² on Day 1, 0.3 mg/m² on Day 8 and 15) intravenously. After CR/CRi is achieved, the dose was reduced to 0.9 mg/m²/cycle (0.3 mg/m² on Day 1, 8 and 15) for 2-3 cycles. The cycle length was 21-28 days. The maximum treatment duration was approximately 52 weeks.	1.2 mg/m²/Cycle (Dose Level 2 Run-in + Randomized) n=64 Participants Participants received a starting dose of inotuzumab ozogamicin 1.2 mg/m²/cycle (0.6 mg/m² on Day 1, 0.3 mg/m² on Days 8 and 15) intravenously. After complete remission (CR)/complete remission with incomplete hematologic recovery (CRi) is achieved, the dose was reduced to 0.9 mg/m²/cycle (0.3 mg/m² on Day 1, 8 and 15). The maximum treatment duration was approximately 52 weeks.	1.8 mg/m²/Cycle (Dose Level 1 Randomized) n=38 Participants Participants received a starting dose of inotuzumab ozogamicin 1.8 mg/m²/cycle (0.8 mg/m² on Day 1, 0.5 mg/m² on Day 8 and 15) intravenously. After CR/CRi is achieved, the dose was reduced to 1.5 mg/m²/cycle (0.5 mg/m² on Day 1, 8 and 15) for 2-3 cycles. The cycle length was 21-28 days. The maximum treatment duration was approximately 52 weeks.
Shift Summary of Hematology Laboratory Test Results From Grade <=2 at Baseline to Grade 3 or 4 Post-Baseline INR increased - Grade 4	NA Participants Grade 4 was not applicable for this test.	NA Participants Grade 4 was not applicable for this test.	NA Participants Grade 4 was not applicable for this test.	NA Participants Grade 4 was not applicable for this test.
Shift Summary of Hematology Laboratory Test Results From Grade <=2 at Baseline to Grade 3 or 4 Post-Baseline Leukocytosis - Grade 3	1 Participants	0 Participants	1 Participants	0 Participants
Shift Summary of Hematology Laboratory Test Results From Grade <=2 at Baseline to Grade 3 or 4 Post-Baseline Leukocytosis - Grade 4	NA Participants Grade 4 was not applicable for this test.	NA Participants Grade 4 was not applicable for this test.	NA Participants Grade 4 was not applicable for this test.	NA Participants Grade 4 was not applicable for this test.
Shift Summary of Hematology Laboratory Test Results From Grade <=2 at Baseline to Grade 3 or 4 Post-Baseline Lymphocyte count decreased - Grade 3	1 Participants	15 Participants	16 Participants	7 Participants
Shift Summary of Hematology Laboratory Test Results From Grade <=2 at Baseline to Grade 3 or 4 Post-Baseline Lymphocyte count decreased - Grade 4	4 Participants	2 Participants	6 Participants	4 Participants
Shift Summary of Hematology Laboratory Test Results From Grade <=2 at Baseline to Grade 3 or 4 Post-Baseline Lymphocyte count increased - Grade 3	2 Participants	1 Participants	3 Participants	3 Participants
Shift Summary of Hematology Laboratory Test Results From Grade <=2 at Baseline to Grade 3 or 4 Post-Baseline Lymphocyte count increased - Grade 4	NA Participants Grade 4 was not applicable for this test.	NA Participants Grade 4 was not applicable for this test.	NA Participants Grade 4 was not applicable for this test.	NA Participants Grade 4 was not applicable for this test.
Shift Summary of Hematology Laboratory Test Results From Grade <=2 at Baseline to Grade 3 or 4 Post-Baseline Neutrophil count decreased - Grade 3	2 Participants	6 Participants	8 Participants	7 Participants
Shift Summary of Hematology Laboratory Test Results From Grade <=2 at Baseline to Grade 3 or 4 Post-Baseline Neutrophil count decreased - Grade 4	11 Participants	10 Participants	21 Participants	9 Participants
Shift Summary of Hematology Laboratory Test Results From Grade <=2 at Baseline to Grade 3 or 4 Post-Baseline Platelet count decreased - Grade 3	1 Participants	6 Participants	7 Participants	5 Participants
Shift Summary of Hematology Laboratory Test Results From Grade <=2 at Baseline to Grade 3 or 4 Post-Baseline Platelet count decreased - Grade 4	4 Participants	3 Participants	7 Participants	7 Participants
Shift Summary of Hematology Laboratory Test Results From Grade <=2 at Baseline to Grade 3 or 4 Post-Baseline White blood cell decreased - Grade 3	5 Participants	13 Participants	18 Participants	9 Participants
Shift Summary of Hematology Laboratory Test Results From Grade <=2 at Baseline to Grade 3 or 4 Post-Baseline White blood cell decreased - Grade 4	7 Participants	10 Participants	17 Participants	11 Participants
Shift Summary of Hematology Laboratory Test Results From Grade <=2 at Baseline to Grade 3 or 4 Post-Baseline Activated partial thromboplastin time prolonged - Grade 3	0 Participants	0 Participants	0 Participants	0 Participants
Shift Summary of Hematology Laboratory Test Results From Grade <=2 at Baseline to Grade 3 or 4 Post-Baseline Activated partial thromboplastin time prolonged - Grade 4	NA Participants Grade 4 was not applicable for this test.	NA Participants Grade 4 was not applicable for this test.	NA Participants Grade 4 was not applicable for this test.	NA Participants Grade 4 was not applicable for this test.
Shift Summary of Hematology Laboratory Test Results From Grade <=2 at Baseline to Grade 3 or 4 Post-Baseline Anemia - Grade 3	8 Participants	13 Participants	21 Participants	11 Participants
Shift Summary of Hematology Laboratory Test Results From Grade <=2 at Baseline to Grade 3 or 4 Post-Baseline Anemia - Grade 4	NA Participants Grade 4 was not applicable for this test.	NA Participants Grade 4 was not applicable for this test.	NA Participants Grade 4 was not applicable for this test.	NA Participants Grade 4 was not applicable for this test.
Shift Summary of Hematology Laboratory Test Results From Grade <=2 at Baseline to Grade 3 or 4 Post-Baseline Hemoglobin increased - Grade 3	0 Participants	0 Participants	0 Participants	0 Participants
Shift Summary of Hematology Laboratory Test Results From Grade <=2 at Baseline to Grade 3 or 4 Post-Baseline Hemoglobin increased - Grade 4	NA Participants Grade 4 was not applicable for this test.	NA Participants Grade 4 was not applicable for this test.	NA Participants Grade 4 was not applicable for this test.	NA Participants Grade 4 was not applicable for this test.
Shift Summary of Hematology Laboratory Test Results From Grade <=2 at Baseline to Grade 3 or 4 Post-Baseline INR increased - Grade 3	0 Participants	0 Participants	0 Participants	0 Participants

SECONDARY outcome

Timeframe: From first dose of study treatment drug through 63 days after last dose (approximately 52 weeks)

Baseline assessment was defined as the last assessment performed on or prior to the date of the first dose of study treatment. Following Parameters were analyzed for laboratory assessment: Chemistry (Alanine aminotransferase increased, Alkaline phosphatase increased, Aspartate aminotransferase increased, Blood bilirubin increased, Chronic kidney disease, Creatinine increased, Gamma glutamyl transpeptidase (GGT) increased, Hypercalcemia, Hyperglycemia, Hyperkalemia, Hypermagnesemia, Hypernatremia, Hypoalbuminemia, Hypocalcemia, Hypoglycemia, Hypokalemia, Hypomagnesemia, Hyponatremia, Hypophosphatemia, Lipase increased and Serum amylase increased). Grades of severity were defined by CTCAE v3.0. Grade 2 = moderate adverse event; Grade 3= severe adverse event; Grade 4 = life-threatening consequences; urgent intervention indicated. Results were reported as of the data cutoff date on 21 Sep 2022.

Outcome measures

Outcome measures
Measure	1.2 mg/m²/Cycle (Dose Level 2 Run-in) n=22 Participants Participants received a starting dose of inotuzumab ozogamicin 1.2 mg/m²/cycle administrated in 3 divided doses (0.6 mg/m² on Day1, 0.3 mg/m² on Days 8 and 15) intravenously. After complete response (CR)/complete remission with incomplete hematologic recovery (CRi) was achieved, the dose was reduced to 0.9 mg/m²/cycle (0.3 mg/m² on Days 1, 8 and 15). The cycle length was 21-28 days. The maximum treatment duration was approximately 52 weeks.	1.2 mg/m²/Cycle (Dose Level 2 Randomized) n=42 Participants Participants received a starting dose of inotuzumab ozogamicin 1.2 mg/m²/cycle (0.6 mg/m² on Day 1, 0.3 mg/m² on Day 8 and 15) intravenously. After CR/CRi is achieved, the dose was reduced to 0.9 mg/m²/cycle (0.3 mg/m² on Day 1, 8 and 15) for 2-3 cycles. The cycle length was 21-28 days. The maximum treatment duration was approximately 52 weeks.	1.2 mg/m²/Cycle (Dose Level 2 Run-in + Randomized) n=64 Participants Participants received a starting dose of inotuzumab ozogamicin 1.2 mg/m²/cycle (0.6 mg/m² on Day 1, 0.3 mg/m² on Days 8 and 15) intravenously. After complete remission (CR)/complete remission with incomplete hematologic recovery (CRi) is achieved, the dose was reduced to 0.9 mg/m²/cycle (0.3 mg/m² on Day 1, 8 and 15). The maximum treatment duration was approximately 52 weeks.	1.8 mg/m²/Cycle (Dose Level 1 Randomized) n=38 Participants Participants received a starting dose of inotuzumab ozogamicin 1.8 mg/m²/cycle (0.8 mg/m² on Day 1, 0.5 mg/m² on Day 8 and 15) intravenously. After CR/CRi is achieved, the dose was reduced to 1.5 mg/m²/cycle (0.5 mg/m² on Day 1, 8 and 15) for 2-3 cycles. The cycle length was 21-28 days. The maximum treatment duration was approximately 52 weeks.
Shift Summary of Chemistry Laboratory Test Results From Grade <=2 at Baseline to Grade 3 or 4 Post-Baseline Alanine aminotransferase increased - Grade 3	1 Participants	0 Participants	1 Participants	0 Participants
Shift Summary of Chemistry Laboratory Test Results From Grade <=2 at Baseline to Grade 3 or 4 Post-Baseline Alanine aminotransferase increased - Grade 4	0 Participants	0 Participants	0 Participants	0 Participants
Shift Summary of Chemistry Laboratory Test Results From Grade <=2 at Baseline to Grade 3 or 4 Post-Baseline Alkaline phosphatase increased - Grade 3	1 Participants	0 Participants	1 Participants	1 Participants
Shift Summary of Chemistry Laboratory Test Results From Grade <=2 at Baseline to Grade 3 or 4 Post-Baseline Alkaline phosphatase increased - Grade 4	0 Participants	0 Participants	0 Participants	0 Participants
Shift Summary of Chemistry Laboratory Test Results From Grade <=2 at Baseline to Grade 3 or 4 Post-Baseline Aspartate aminotransferase increased - Grade 3	1 Participants	3 Participants	4 Participants	0 Participants
Shift Summary of Chemistry Laboratory Test Results From Grade <=2 at Baseline to Grade 3 or 4 Post-Baseline Aspartate aminotransferase increased - Grade 4	0 Participants	0 Participants	0 Participants	0 Participants
Shift Summary of Chemistry Laboratory Test Results From Grade <=2 at Baseline to Grade 3 or 4 Post-Baseline Blood bilirubin increased - Grade 3	1 Participants	1 Participants	2 Participants	0 Participants
Shift Summary of Chemistry Laboratory Test Results From Grade <=2 at Baseline to Grade 3 or 4 Post-Baseline Blood bilirubin increased - Grade 4	0 Participants	0 Participants	0 Participants	0 Participants
Shift Summary of Chemistry Laboratory Test Results From Grade <=2 at Baseline to Grade 3 or 4 Post-Baseline Chronic kidney disease - Grade 3	0 Participants	0 Participants	0 Participants	0 Participants
Shift Summary of Chemistry Laboratory Test Results From Grade <=2 at Baseline to Grade 3 or 4 Post-Baseline Chronic kidney disease - Grade 4	0 Participants	0 Participants	0 Participants	0 Participants
Shift Summary of Chemistry Laboratory Test Results From Grade <=2 at Baseline to Grade 3 or 4 Post-Baseline Creatinine increased - Grade 3	0 Participants	0 Participants	0 Participants	0 Participants
Shift Summary of Chemistry Laboratory Test Results From Grade <=2 at Baseline to Grade 3 or 4 Post-Baseline Creatinine increased - Grade 4	0 Participants	0 Participants	0 Participants	0 Participants
Shift Summary of Chemistry Laboratory Test Results From Grade <=2 at Baseline to Grade 3 or 4 Post-Baseline GGT increased - Grade 3	1 Participants	2 Participants	3 Participants	3 Participants
Shift Summary of Chemistry Laboratory Test Results From Grade <=2 at Baseline to Grade 3 or 4 Post-Baseline GGT increased - Grade 4	0 Participants	0 Participants	0 Participants	0 Participants
Shift Summary of Chemistry Laboratory Test Results From Grade <=2 at Baseline to Grade 3 or 4 Post-Baseline Hypercalcemia - Grade 3	0 Participants	0 Participants	0 Participants	0 Participants
Shift Summary of Chemistry Laboratory Test Results From Grade <=2 at Baseline to Grade 3 or 4 Post-Baseline Hypercalcemia - Grade 4	0 Participants	0 Participants	0 Participants	0 Participants
Shift Summary of Chemistry Laboratory Test Results From Grade <=2 at Baseline to Grade 3 or 4 Post-Baseline Hyperglycemia - Grade 3	2 Participants	2 Participants	4 Participants	2 Participants
Shift Summary of Chemistry Laboratory Test Results From Grade <=2 at Baseline to Grade 3 or 4 Post-Baseline Hyperglycemia - Grade 4	0 Participants	0 Participants	0 Participants	0 Participants
Shift Summary of Chemistry Laboratory Test Results From Grade <=2 at Baseline to Grade 3 or 4 Post-Baseline Hyperkalemia - Grade 3	0 Participants	0 Participants	0 Participants	0 Participants
Shift Summary of Chemistry Laboratory Test Results From Grade <=2 at Baseline to Grade 3 or 4 Post-Baseline Hyperkalemia - Grade 4	1 Participants	0 Participants	1 Participants	0 Participants
Shift Summary of Chemistry Laboratory Test Results From Grade <=2 at Baseline to Grade 3 or 4 Post-Baseline Hypermagnesemia - Grade 3	1 Participants	0 Participants	1 Participants	1 Participants
Shift Summary of Chemistry Laboratory Test Results From Grade <=2 at Baseline to Grade 3 or 4 Post-Baseline Hypermagnesemia - Grade 4	0 Participants	0 Participants	0 Participants	0 Participants
Shift Summary of Chemistry Laboratory Test Results From Grade <=2 at Baseline to Grade 3 or 4 Post-Baseline Hypernatremia - Grade 3	0 Participants	0 Participants	0 Participants	0 Participants
Shift Summary of Chemistry Laboratory Test Results From Grade <=2 at Baseline to Grade 3 or 4 Post-Baseline Hypernatremia - Grade 4	0 Participants	1 Participants	1 Participants	0 Participants
Shift Summary of Chemistry Laboratory Test Results From Grade <=2 at Baseline to Grade 3 or 4 Post-Baseline Hypoalbuminemia - Grade 3	1 Participants	3 Participants	4 Participants	3 Participants
Shift Summary of Chemistry Laboratory Test Results From Grade <=2 at Baseline to Grade 3 or 4 Post-Baseline Hypoalbuminemia - Grade 4	NA Participants Grade 4 was not applicable for this test.	NA Participants Grade 4 was not applicable for this test.	NA Participants Grade 4 was not applicable for this test.	NA Participants Grade 4 was not applicable for this test.
Shift Summary of Chemistry Laboratory Test Results From Grade <=2 at Baseline to Grade 3 or 4 Post-Baseline Hypocalcemia - Grade 3	1 Participants	0 Participants	1 Participants	0 Participants
Shift Summary of Chemistry Laboratory Test Results From Grade <=2 at Baseline to Grade 3 or 4 Post-Baseline Hypocalcemia - Grade 4	0 Participants	0 Participants	0 Participants	0 Participants
Shift Summary of Chemistry Laboratory Test Results From Grade <=2 at Baseline to Grade 3 or 4 Post-Baseline Hypoglycemia - Grade 3	0 Participants	0 Participants	0 Participants	0 Participants
Shift Summary of Chemistry Laboratory Test Results From Grade <=2 at Baseline to Grade 3 or 4 Post-Baseline Hypoglycemia - Grade 4	0 Participants	0 Participants	0 Participants	0 Participants
Shift Summary of Chemistry Laboratory Test Results From Grade <=2 at Baseline to Grade 3 or 4 Post-Baseline Hypokalemia - Grade 3	1 Participants	2 Participants	3 Participants	1 Participants
Shift Summary of Chemistry Laboratory Test Results From Grade <=2 at Baseline to Grade 3 or 4 Post-Baseline Hypokalemia - Grade 4	1 Participants	0 Participants	1 Participants	0 Participants
Shift Summary of Chemistry Laboratory Test Results From Grade <=2 at Baseline to Grade 3 or 4 Post-Baseline Hypomagnesemia - Grade 3	1 Participants	0 Participants	1 Participants	1 Participants
Shift Summary of Chemistry Laboratory Test Results From Grade <=2 at Baseline to Grade 3 or 4 Post-Baseline Hypomagnesemia - Grade 4	0 Participants	0 Participants	0 Participants	1 Participants
Shift Summary of Chemistry Laboratory Test Results From Grade <=2 at Baseline to Grade 3 or 4 Post-Baseline Hyponatremia - Grade 3	1 Participants	0 Participants	1 Participants	0 Participants
Shift Summary of Chemistry Laboratory Test Results From Grade <=2 at Baseline to Grade 3 or 4 Post-Baseline Hyponatremia - Grade 4	0 Participants	0 Participants	0 Participants	0 Participants
Shift Summary of Chemistry Laboratory Test Results From Grade <=2 at Baseline to Grade 3 or 4 Post-Baseline Hypophosphatemia- Grade 3	2 Participants	0 Participants	2 Participants	1 Participants
Shift Summary of Chemistry Laboratory Test Results From Grade <=2 at Baseline to Grade 3 or 4 Post-Baseline Hypophosphatemia - Grade 4	0 Participants	0 Participants	0 Participants	1 Participants
Shift Summary of Chemistry Laboratory Test Results From Grade <=2 at Baseline to Grade 3 or 4 Post-Baseline Lipase increased - Grade 3	3 Participants	3 Participants	6 Participants	2 Participants
Shift Summary of Chemistry Laboratory Test Results From Grade <=2 at Baseline to Grade 3 or 4 Post-Baseline Lipase increased - Grade 4	0 Participants	2 Participants	2 Participants	0 Participants
Shift Summary of Chemistry Laboratory Test Results From Grade <=2 at Baseline to Grade 3 or 4 Post-Baseline Serum amylase increased - Grade 3	1 Participants	1 Participants	2 Participants	0 Participants
Shift Summary of Chemistry Laboratory Test Results From Grade <=2 at Baseline to Grade 3 or 4 Post-Baseline Serum amylase increased - Grade 4	0 Participants	0 Participants	0 Participants	0 Participants

SECONDARY outcome

Timeframe: At screening, once at Day 16-28 of Cycles 1 and 2, or until CR/CRi and MRD negativity were achieved, then after every 1-2 cycles as clinically indicated, and at EOT visit (maximum of 2.5 years)

Population: All participants who were randomized into the study and achieved CR/CRi.

MRD was assessed by flow cytometry for CD22 and other cell surface markers associated with B-cell ALL. In participants who achieved CR/CRi, MRD negativity was defined as defined as \<1 abnormal cell/10\^4 nucleated cells by flow cytometry per central laboratory analysis.

Outcome measures

Outcome measures
Measure	1.2 mg/m²/Cycle (Dose Level 2 Run-in) n=11 Participants Participants received a starting dose of inotuzumab ozogamicin 1.2 mg/m²/cycle administrated in 3 divided doses (0.6 mg/m² on Day1, 0.3 mg/m² on Days 8 and 15) intravenously. After complete response (CR)/complete remission with incomplete hematologic recovery (CRi) was achieved, the dose was reduced to 0.9 mg/m²/cycle (0.3 mg/m² on Days 1, 8 and 15). The cycle length was 21-28 days. The maximum treatment duration was approximately 52 weeks.	1.2 mg/m²/Cycle (Dose Level 2 Randomized) n=35 Participants Participants received a starting dose of inotuzumab ozogamicin 1.2 mg/m²/cycle (0.6 mg/m² on Day 1, 0.3 mg/m² on Day 8 and 15) intravenously. After CR/CRi is achieved, the dose was reduced to 0.9 mg/m²/cycle (0.3 mg/m² on Day 1, 8 and 15) for 2-3 cycles. The cycle length was 21-28 days. The maximum treatment duration was approximately 52 weeks.	1.2 mg/m²/Cycle (Dose Level 2 Run-in + Randomized) n=46 Participants Participants received a starting dose of inotuzumab ozogamicin 1.2 mg/m²/cycle (0.6 mg/m² on Day 1, 0.3 mg/m² on Days 8 and 15) intravenously. After complete remission (CR)/complete remission with incomplete hematologic recovery (CRi) is achieved, the dose was reduced to 0.9 mg/m²/cycle (0.3 mg/m² on Day 1, 8 and 15). The maximum treatment duration was approximately 52 weeks.	1.8 mg/m²/Cycle (Dose Level 1 Randomized) n=26 Participants Participants received a starting dose of inotuzumab ozogamicin 1.8 mg/m²/cycle (0.8 mg/m² on Day 1, 0.5 mg/m² on Day 8 and 15) intravenously. After CR/CRi is achieved, the dose was reduced to 1.5 mg/m²/cycle (0.5 mg/m² on Day 1, 8 and 15) for 2-3 cycles. The cycle length was 21-28 days. The maximum treatment duration was approximately 52 weeks.
Number of Participants Achieving a CR/CRi With Minimal Residual Disease (MRD) Negativity	8 Participants	25 Participants	33 Participants	18 Participants

SECONDARY outcome

Timeframe: From first dose of study treatment of 6 cycles till follow-up up to 2 years, in total approximately 2.5 years

Population: Participants who were randomized into the study and with a remission (CR/CRi).

DoR was defined as time from date of first response in responders (CR/CRi) to the date of disease progression (i.e., objective progression, relapse from CR/CRi, including post-study treatment follow-up disease assessments) or death due to any cause, whichever occurs first. DoR was estimated using Kaplan-Meier methods. Results were reported as of the data cutoff date on 21 Sep 2022.

Outcome measures

Outcome measures
Measure	1.2 mg/m²/Cycle (Dose Level 2 Run-in) n=11 Participants Participants received a starting dose of inotuzumab ozogamicin 1.2 mg/m²/cycle administrated in 3 divided doses (0.6 mg/m² on Day1, 0.3 mg/m² on Days 8 and 15) intravenously. After complete response (CR)/complete remission with incomplete hematologic recovery (CRi) was achieved, the dose was reduced to 0.9 mg/m²/cycle (0.3 mg/m² on Days 1, 8 and 15). The cycle length was 21-28 days. The maximum treatment duration was approximately 52 weeks.	1.2 mg/m²/Cycle (Dose Level 2 Randomized) n=35 Participants Participants received a starting dose of inotuzumab ozogamicin 1.2 mg/m²/cycle (0.6 mg/m² on Day 1, 0.3 mg/m² on Day 8 and 15) intravenously. After CR/CRi is achieved, the dose was reduced to 0.9 mg/m²/cycle (0.3 mg/m² on Day 1, 8 and 15) for 2-3 cycles. The cycle length was 21-28 days. The maximum treatment duration was approximately 52 weeks.	1.2 mg/m²/Cycle (Dose Level 2 Run-in + Randomized) n=46 Participants Participants received a starting dose of inotuzumab ozogamicin 1.2 mg/m²/cycle (0.6 mg/m² on Day 1, 0.3 mg/m² on Days 8 and 15) intravenously. After complete remission (CR)/complete remission with incomplete hematologic recovery (CRi) is achieved, the dose was reduced to 0.9 mg/m²/cycle (0.3 mg/m² on Day 1, 8 and 15). The maximum treatment duration was approximately 52 weeks.	1.8 mg/m²/Cycle (Dose Level 1 Randomized) n=26 Participants Participants received a starting dose of inotuzumab ozogamicin 1.8 mg/m²/cycle (0.8 mg/m² on Day 1, 0.5 mg/m² on Day 8 and 15) intravenously. After CR/CRi is achieved, the dose was reduced to 1.5 mg/m²/cycle (0.5 mg/m² on Day 1, 8 and 15) for 2-3 cycles. The cycle length was 21-28 days. The maximum treatment duration was approximately 52 weeks.
Duration of Remission (DoR) in Participants Achieving CR/CRi	5.2 Months Interval 1.9 to The upper limit was not estimated due to fewer number of participants with event.	6.5 Months Interval 4.6 to 20.9	5.5 Months Interval 4.6 to 20.9	6.8 Months Interval 4.7 to 8.7

SECONDARY outcome

Timeframe: From first dose of study treatment of 6 cycles till follow-up up to 2 years, in total approximately 2.5 years

Population: All participants who were randomized into the study with study drug assignment based on randomization.

PFS was defined as time from date of randomization to the date of disease progression (i.e., objective progression, relapse from CR/CRi, including post-study treatment follow-up disease assessments), death due to any cause, or starting new induction therapy/post-therapy HSCT without achieving CR/CRi, whichever occured first. PFS was estimated using Kaplan-Meier methods. Results were reported as of the data cutoff date on 21 Sep 2022.

Outcome measures

Outcome measures
Measure	1.2 mg/m²/Cycle (Dose Level 2 Run-in) n=22 Participants Participants received a starting dose of inotuzumab ozogamicin 1.2 mg/m²/cycle administrated in 3 divided doses (0.6 mg/m² on Day1, 0.3 mg/m² on Days 8 and 15) intravenously. After complete response (CR)/complete remission with incomplete hematologic recovery (CRi) was achieved, the dose was reduced to 0.9 mg/m²/cycle (0.3 mg/m² on Days 1, 8 and 15). The cycle length was 21-28 days. The maximum treatment duration was approximately 52 weeks.	1.2 mg/m²/Cycle (Dose Level 2 Randomized) n=42 Participants Participants received a starting dose of inotuzumab ozogamicin 1.2 mg/m²/cycle (0.6 mg/m² on Day 1, 0.3 mg/m² on Day 8 and 15) intravenously. After CR/CRi is achieved, the dose was reduced to 0.9 mg/m²/cycle (0.3 mg/m² on Day 1, 8 and 15) for 2-3 cycles. The cycle length was 21-28 days. The maximum treatment duration was approximately 52 weeks.	1.2 mg/m²/Cycle (Dose Level 2 Run-in + Randomized) n=64 Participants Participants received a starting dose of inotuzumab ozogamicin 1.2 mg/m²/cycle (0.6 mg/m² on Day 1, 0.3 mg/m² on Days 8 and 15) intravenously. After complete remission (CR)/complete remission with incomplete hematologic recovery (CRi) is achieved, the dose was reduced to 0.9 mg/m²/cycle (0.3 mg/m² on Day 1, 8 and 15). The maximum treatment duration was approximately 52 weeks.	1.8 mg/m²/Cycle (Dose Level 1 Randomized) n=38 Participants Participants received a starting dose of inotuzumab ozogamicin 1.8 mg/m²/cycle (0.8 mg/m² on Day 1, 0.5 mg/m² on Day 8 and 15) intravenously. After CR/CRi is achieved, the dose was reduced to 1.5 mg/m²/cycle (0.5 mg/m² on Day 1, 8 and 15) for 2-3 cycles. The cycle length was 21-28 days. The maximum treatment duration was approximately 52 weeks.
Progression-Free Survival	2.9 Months Interval 1.7 to 5.8	6.3 Months Interval 4.8 to 10.0	5.3 Months Interval 3.4 to 7.2	6.3 Months Interval 2.8 to 8.0

SECONDARY outcome

Timeframe: From first dose of study treatment of 6 cycles till follow-up up to 2 years, in total approximately 2.5 years

Population: All patients who were randomized into the study with study drug assignment based on randomization.

Overall survival was defined as the time from date of first dose of study treatment to death due to any cause. Participants without confirmation of death were censored at the date that the participant was last known to be alive. Results were reported as of the data cutoff date on 21 Sep 2022.

Outcome measures

Outcome measures
Measure	1.2 mg/m²/Cycle (Dose Level 2 Run-in) n=22 Participants Participants received a starting dose of inotuzumab ozogamicin 1.2 mg/m²/cycle administrated in 3 divided doses (0.6 mg/m² on Day1, 0.3 mg/m² on Days 8 and 15) intravenously. After complete response (CR)/complete remission with incomplete hematologic recovery (CRi) was achieved, the dose was reduced to 0.9 mg/m²/cycle (0.3 mg/m² on Days 1, 8 and 15). The cycle length was 21-28 days. The maximum treatment duration was approximately 52 weeks.	1.2 mg/m²/Cycle (Dose Level 2 Randomized) n=42 Participants Participants received a starting dose of inotuzumab ozogamicin 1.2 mg/m²/cycle (0.6 mg/m² on Day 1, 0.3 mg/m² on Day 8 and 15) intravenously. After CR/CRi is achieved, the dose was reduced to 0.9 mg/m²/cycle (0.3 mg/m² on Day 1, 8 and 15) for 2-3 cycles. The cycle length was 21-28 days. The maximum treatment duration was approximately 52 weeks.	1.2 mg/m²/Cycle (Dose Level 2 Run-in + Randomized) n=64 Participants Participants received a starting dose of inotuzumab ozogamicin 1.2 mg/m²/cycle (0.6 mg/m² on Day 1, 0.3 mg/m² on Days 8 and 15) intravenously. After complete remission (CR)/complete remission with incomplete hematologic recovery (CRi) is achieved, the dose was reduced to 0.9 mg/m²/cycle (0.3 mg/m² on Day 1, 8 and 15). The maximum treatment duration was approximately 52 weeks.	1.8 mg/m²/Cycle (Dose Level 1 Randomized) n=38 Participants Participants received a starting dose of inotuzumab ozogamicin 1.8 mg/m²/cycle (0.8 mg/m² on Day 1, 0.5 mg/m² on Day 8 and 15) intravenously. After CR/CRi is achieved, the dose was reduced to 1.5 mg/m²/cycle (0.5 mg/m² on Day 1, 8 and 15) for 2-3 cycles. The cycle length was 21-28 days. The maximum treatment duration was approximately 52 weeks.
Overall Survival	4.5 Months Interval 3.2 to 8.6	9.6 Months Interval 6.4 to The upper limit was not estimable due to fewer number of participants with event.	7.6 Months Interval 5.8 to 10.0	8.1 Months Interval 5.4 to 10.4

SECONDARY outcome

Timeframe: From first dose of study treatment of 6 cycles till follow-up up to 2 years, in total approximately 2.5 years

Population: All participants who were randomized into the study with study drug assignment based on randomization.

Participants who underwent HSCT after inotuzumab ozogamicin treatment. Results were reported as of the data cutoff date on 21 Sep 2022.

Outcome measures

Outcome measures
Measure	1.2 mg/m²/Cycle (Dose Level 2 Run-in) n=22 Participants Participants received a starting dose of inotuzumab ozogamicin 1.2 mg/m²/cycle administrated in 3 divided doses (0.6 mg/m² on Day1, 0.3 mg/m² on Days 8 and 15) intravenously. After complete response (CR)/complete remission with incomplete hematologic recovery (CRi) was achieved, the dose was reduced to 0.9 mg/m²/cycle (0.3 mg/m² on Days 1, 8 and 15). The cycle length was 21-28 days. The maximum treatment duration was approximately 52 weeks.	1.2 mg/m²/Cycle (Dose Level 2 Randomized) n=42 Participants Participants received a starting dose of inotuzumab ozogamicin 1.2 mg/m²/cycle (0.6 mg/m² on Day 1, 0.3 mg/m² on Day 8 and 15) intravenously. After CR/CRi is achieved, the dose was reduced to 0.9 mg/m²/cycle (0.3 mg/m² on Day 1, 8 and 15) for 2-3 cycles. The cycle length was 21-28 days. The maximum treatment duration was approximately 52 weeks.	1.2 mg/m²/Cycle (Dose Level 2 Run-in + Randomized) n=64 Participants Participants received a starting dose of inotuzumab ozogamicin 1.2 mg/m²/cycle (0.6 mg/m² on Day 1, 0.3 mg/m² on Days 8 and 15) intravenously. After complete remission (CR)/complete remission with incomplete hematologic recovery (CRi) is achieved, the dose was reduced to 0.9 mg/m²/cycle (0.3 mg/m² on Day 1, 8 and 15). The maximum treatment duration was approximately 52 weeks.	1.8 mg/m²/Cycle (Dose Level 1 Randomized) n=38 Participants Participants received a starting dose of inotuzumab ozogamicin 1.8 mg/m²/cycle (0.8 mg/m² on Day 1, 0.5 mg/m² on Day 8 and 15) intravenously. After CR/CRi is achieved, the dose was reduced to 1.5 mg/m²/cycle (0.5 mg/m² on Day 1, 8 and 15) for 2-3 cycles. The cycle length was 21-28 days. The maximum treatment duration was approximately 52 weeks.
Number of Participant Received HSCT Post Inotuzumab Ozogamicin Treatment	10 Participants	21 Participants	31 Participants	12 Participants

SECONDARY outcome

Timeframe: From first dose of study treatment to Month 12

Population: All participants who were randomized into the study with study drug assignment based on randomization and who were post HSCT.

Post-HSCT relapse is defined as the time from date of first HSCT after inotuzumab ozogamicin treatment to the date of first relapse post-HSCT. Cumulative incidence rates of an event at a particular timepoint were estimated with the CI calculated based on the cumulative incidence function using the method described by Kalbfleisch RL and Prentice JD. Results were reported as of the data cutoff date on 21 Sep 2022.

Outcome measures

Outcome measures
Measure	1.2 mg/m²/Cycle (Dose Level 2 Run-in) n=10 Participants Participants received a starting dose of inotuzumab ozogamicin 1.2 mg/m²/cycle administrated in 3 divided doses (0.6 mg/m² on Day1, 0.3 mg/m² on Days 8 and 15) intravenously. After complete response (CR)/complete remission with incomplete hematologic recovery (CRi) was achieved, the dose was reduced to 0.9 mg/m²/cycle (0.3 mg/m² on Days 1, 8 and 15). The cycle length was 21-28 days. The maximum treatment duration was approximately 52 weeks.	1.2 mg/m²/Cycle (Dose Level 2 Randomized) n=21 Participants Participants received a starting dose of inotuzumab ozogamicin 1.2 mg/m²/cycle (0.6 mg/m² on Day 1, 0.3 mg/m² on Day 8 and 15) intravenously. After CR/CRi is achieved, the dose was reduced to 0.9 mg/m²/cycle (0.3 mg/m² on Day 1, 8 and 15) for 2-3 cycles. The cycle length was 21-28 days. The maximum treatment duration was approximately 52 weeks.	1.2 mg/m²/Cycle (Dose Level 2 Run-in + Randomized) n=31 Participants Participants received a starting dose of inotuzumab ozogamicin 1.2 mg/m²/cycle (0.6 mg/m² on Day 1, 0.3 mg/m² on Days 8 and 15) intravenously. After complete remission (CR)/complete remission with incomplete hematologic recovery (CRi) is achieved, the dose was reduced to 0.9 mg/m²/cycle (0.3 mg/m² on Day 1, 8 and 15). The maximum treatment duration was approximately 52 weeks.	1.8 mg/m²/Cycle (Dose Level 1 Randomized) n=12 Participants Participants received a starting dose of inotuzumab ozogamicin 1.8 mg/m²/cycle (0.8 mg/m² on Day 1, 0.5 mg/m² on Day 8 and 15) intravenously. After CR/CRi is achieved, the dose was reduced to 1.5 mg/m²/cycle (0.5 mg/m² on Day 1, 8 and 15) for 2-3 cycles. The cycle length was 21-28 days. The maximum treatment duration was approximately 52 weeks.
The Cumulative Incidence Rate of Post-HSCT Relapse at Month 12	11.11 Percentages of participants Interval 0.4 to 41.66	22.53 Percentages of participants Interval 6.39 to 44.59	18.65 Percentages of participants Interval 6.46 to 35.72	16.67 Percentages of participants Interval 2.26 to 42.89

SECONDARY outcome

Timeframe: From first dose of study treatment of 6 cycles till follow-up up to 2 years, in total approximately 2.5 years

Population: All participants who were randomized into the study with study drug assignment based on randomization and who were post HSCT.

Post-HSCT Mortality was defined as the time from date of first HSCT after inotuzumab ozogamicin treatment to death due to any cause. Results were reported as of the data cutoff date on 21 Sep 2022.

Outcome measures

Outcome measures
Measure	1.2 mg/m²/Cycle (Dose Level 2 Run-in) n=10 Participants Participants received a starting dose of inotuzumab ozogamicin 1.2 mg/m²/cycle administrated in 3 divided doses (0.6 mg/m² on Day1, 0.3 mg/m² on Days 8 and 15) intravenously. After complete response (CR)/complete remission with incomplete hematologic recovery (CRi) was achieved, the dose was reduced to 0.9 mg/m²/cycle (0.3 mg/m² on Days 1, 8 and 15). The cycle length was 21-28 days. The maximum treatment duration was approximately 52 weeks.	1.2 mg/m²/Cycle (Dose Level 2 Randomized) n=21 Participants Participants received a starting dose of inotuzumab ozogamicin 1.2 mg/m²/cycle (0.6 mg/m² on Day 1, 0.3 mg/m² on Day 8 and 15) intravenously. After CR/CRi is achieved, the dose was reduced to 0.9 mg/m²/cycle (0.3 mg/m² on Day 1, 8 and 15) for 2-3 cycles. The cycle length was 21-28 days. The maximum treatment duration was approximately 52 weeks.	1.2 mg/m²/Cycle (Dose Level 2 Run-in + Randomized) n=31 Participants Participants received a starting dose of inotuzumab ozogamicin 1.2 mg/m²/cycle (0.6 mg/m² on Day 1, 0.3 mg/m² on Days 8 and 15) intravenously. After complete remission (CR)/complete remission with incomplete hematologic recovery (CRi) is achieved, the dose was reduced to 0.9 mg/m²/cycle (0.3 mg/m² on Day 1, 8 and 15). The maximum treatment duration was approximately 52 weeks.	1.8 mg/m²/Cycle (Dose Level 1 Randomized) n=12 Participants Participants received a starting dose of inotuzumab ozogamicin 1.8 mg/m²/cycle (0.8 mg/m² on Day 1, 0.5 mg/m² on Day 8 and 15) intravenously. After CR/CRi is achieved, the dose was reduced to 1.5 mg/m²/cycle (0.5 mg/m² on Day 1, 8 and 15) for 2-3 cycles. The cycle length was 21-28 days. The maximum treatment duration was approximately 52 weeks.
Number of Participants With Post-HSCT Mortality	6 Participants	8 Participants	14 Participants	5 Participants

SECONDARY outcome

Timeframe: From first dose of study treatment of 6 cycles till follow-up up to 2 years, in total approximately 2.5 years

Population: All participants who were randomized into the study with study drug assignment based on randomization and who underwent HSCT after inotuzumab ozogamicin treatment.

Post HSCT non-relapse mortality was defined as time from date of first HSCT after inotuzumab ozogamicin treatment to death due to any cause without prior relapse. Results were reported as of the data cutoff date on 21 Sep 2022.

Outcome measures

Outcome measures
Measure	1.2 mg/m²/Cycle (Dose Level 2 Run-in) n=10 Participants Participants received a starting dose of inotuzumab ozogamicin 1.2 mg/m²/cycle administrated in 3 divided doses (0.6 mg/m² on Day1, 0.3 mg/m² on Days 8 and 15) intravenously. After complete response (CR)/complete remission with incomplete hematologic recovery (CRi) was achieved, the dose was reduced to 0.9 mg/m²/cycle (0.3 mg/m² on Days 1, 8 and 15). The cycle length was 21-28 days. The maximum treatment duration was approximately 52 weeks.	1.2 mg/m²/Cycle (Dose Level 2 Randomized) n=21 Participants Participants received a starting dose of inotuzumab ozogamicin 1.2 mg/m²/cycle (0.6 mg/m² on Day 1, 0.3 mg/m² on Day 8 and 15) intravenously. After CR/CRi is achieved, the dose was reduced to 0.9 mg/m²/cycle (0.3 mg/m² on Day 1, 8 and 15) for 2-3 cycles. The cycle length was 21-28 days. The maximum treatment duration was approximately 52 weeks.	1.2 mg/m²/Cycle (Dose Level 2 Run-in + Randomized) n=31 Participants Participants received a starting dose of inotuzumab ozogamicin 1.2 mg/m²/cycle (0.6 mg/m² on Day 1, 0.3 mg/m² on Days 8 and 15) intravenously. After complete remission (CR)/complete remission with incomplete hematologic recovery (CRi) is achieved, the dose was reduced to 0.9 mg/m²/cycle (0.3 mg/m² on Day 1, 8 and 15). The maximum treatment duration was approximately 52 weeks.	1.8 mg/m²/Cycle (Dose Level 1 Randomized) n=12 Participants Participants received a starting dose of inotuzumab ozogamicin 1.8 mg/m²/cycle (0.8 mg/m² on Day 1, 0.5 mg/m² on Day 8 and 15) intravenously. After CR/CRi is achieved, the dose was reduced to 1.5 mg/m²/cycle (0.5 mg/m² on Day 1, 8 and 15) for 2-3 cycles. The cycle length was 21-28 days. The maximum treatment duration was approximately 52 weeks.
Number of Participants With Post HSCT Non-Relapse Mortality	5 Participants	5 Participants	10 Participants	4 Participants

SECONDARY outcome

Timeframe: From first dose of study treatment of 6 cycles till follow-up up to 2 years, in total approximately 2.5 years

Population: All participants who were randomized into the study with study drug assignment based on randomization and who underwent HSCT after inotuzumab ozogamicin treatment.

Post HSCT Relapse-Related Mortality was defined as time from date of first HSCT after inotuzumab ozogamicin treatment to death due to any cause with prior relapse. Results were reported as of the data cutoff date on 21 Sep 2022.

Outcome measures

Outcome measures
Measure	1.2 mg/m²/Cycle (Dose Level 2 Run-in) n=10 Participants Participants received a starting dose of inotuzumab ozogamicin 1.2 mg/m²/cycle administrated in 3 divided doses (0.6 mg/m² on Day1, 0.3 mg/m² on Days 8 and 15) intravenously. After complete response (CR)/complete remission with incomplete hematologic recovery (CRi) was achieved, the dose was reduced to 0.9 mg/m²/cycle (0.3 mg/m² on Days 1, 8 and 15). The cycle length was 21-28 days. The maximum treatment duration was approximately 52 weeks.	1.2 mg/m²/Cycle (Dose Level 2 Randomized) n=21 Participants Participants received a starting dose of inotuzumab ozogamicin 1.2 mg/m²/cycle (0.6 mg/m² on Day 1, 0.3 mg/m² on Day 8 and 15) intravenously. After CR/CRi is achieved, the dose was reduced to 0.9 mg/m²/cycle (0.3 mg/m² on Day 1, 8 and 15) for 2-3 cycles. The cycle length was 21-28 days. The maximum treatment duration was approximately 52 weeks.	1.2 mg/m²/Cycle (Dose Level 2 Run-in + Randomized) n=31 Participants Participants received a starting dose of inotuzumab ozogamicin 1.2 mg/m²/cycle (0.6 mg/m² on Day 1, 0.3 mg/m² on Days 8 and 15) intravenously. After complete remission (CR)/complete remission with incomplete hematologic recovery (CRi) is achieved, the dose was reduced to 0.9 mg/m²/cycle (0.3 mg/m² on Day 1, 8 and 15). The maximum treatment duration was approximately 52 weeks.	1.8 mg/m²/Cycle (Dose Level 1 Randomized) n=12 Participants Participants received a starting dose of inotuzumab ozogamicin 1.8 mg/m²/cycle (0.8 mg/m² on Day 1, 0.5 mg/m² on Day 8 and 15) intravenously. After CR/CRi is achieved, the dose was reduced to 1.5 mg/m²/cycle (0.5 mg/m² on Day 1, 8 and 15) for 2-3 cycles. The cycle length was 21-28 days. The maximum treatment duration was approximately 52 weeks.
Number of Participants With Post HSCT Relapse-Related Mortality	1 Participants	3 Participants	4 Participants	1 Participants

SECONDARY outcome

Timeframe: Pre-dose on Cycle 1 Day 1, 8 and 15, and on Day1 and 8 of Cycle 2, 3 and 4.

Population: All treated participants who received at least 1 dose of study drug and had at least one PK sample collected and analyzed. 'Number analyzed' = Participants evaluable for this outcome measure for each specified row.

Ctrough was defined as the mean Predose concentration of study treatment.

Outcome measures

Outcome measures
Measure	1.2 mg/m²/Cycle (Dose Level 2 Run-in) n=22 Participants Participants received a starting dose of inotuzumab ozogamicin 1.2 mg/m²/cycle administrated in 3 divided doses (0.6 mg/m² on Day1, 0.3 mg/m² on Days 8 and 15) intravenously. After complete response (CR)/complete remission with incomplete hematologic recovery (CRi) was achieved, the dose was reduced to 0.9 mg/m²/cycle (0.3 mg/m² on Days 1, 8 and 15). The cycle length was 21-28 days. The maximum treatment duration was approximately 52 weeks.	1.2 mg/m²/Cycle (Dose Level 2 Randomized) n=42 Participants Participants received a starting dose of inotuzumab ozogamicin 1.2 mg/m²/cycle (0.6 mg/m² on Day 1, 0.3 mg/m² on Day 8 and 15) intravenously. After CR/CRi is achieved, the dose was reduced to 0.9 mg/m²/cycle (0.3 mg/m² on Day 1, 8 and 15) for 2-3 cycles. The cycle length was 21-28 days. The maximum treatment duration was approximately 52 weeks.	1.2 mg/m²/Cycle (Dose Level 2 Run-in + Randomized) n=64 Participants Participants received a starting dose of inotuzumab ozogamicin 1.2 mg/m²/cycle (0.6 mg/m² on Day 1, 0.3 mg/m² on Days 8 and 15) intravenously. After complete remission (CR)/complete remission with incomplete hematologic recovery (CRi) is achieved, the dose was reduced to 0.9 mg/m²/cycle (0.3 mg/m² on Day 1, 8 and 15). The maximum treatment duration was approximately 52 weeks.	1.8 mg/m²/Cycle (Dose Level 1 Randomized) n=38 Participants Participants received a starting dose of inotuzumab ozogamicin 1.8 mg/m²/cycle (0.8 mg/m² on Day 1, 0.5 mg/m² on Day 8 and 15) intravenously. After CR/CRi is achieved, the dose was reduced to 1.5 mg/m²/cycle (0.5 mg/m² on Day 1, 8 and 15) for 2-3 cycles. The cycle length was 21-28 days. The maximum treatment duration was approximately 52 weeks.
Mean Predose Concentrations (Ctrough) of Inotuzumab Ozogamicin Cycle 1 Day 1 (C1D1)	1.9 ng/mL Standard Deviation 9.10	0.5 ng/mL Standard Deviation 1.97	1.3 ng/mL Standard Deviation 6.77	0.0 ng/mL Standard Deviation 0.00
Mean Predose Concentrations (Ctrough) of Inotuzumab Ozogamicin C1D8	7.7 ng/mL Standard Deviation 20.53	5.0 ng/mL Standard Deviation 5.83	6.4 ng/mL Standard Deviation 15.61	5.4 ng/mL Standard Deviation 7.71
Mean Predose Concentrations (Ctrough) of Inotuzumab Ozogamicin C1D15	8.9 ng/mL Standard Deviation 11.14	27.3 ng/mL Standard Deviation 52.32	17.4 ng/mL Standard Deviation 37.09	25.3 ng/mL Standard Deviation 19.47
Mean Predose Concentrations (Ctrough) of Inotuzumab Ozogamicin C2D1	16.4 ng/mL Standard Deviation 21.43	18.8 ng/mL Standard Deviation 37.80	17.6 ng/mL Standard Deviation 30.02	39.7 ng/mL Standard Deviation 73.86
Mean Predose Concentrations (Ctrough) of Inotuzumab Ozogamicin C2D8	42.6 ng/mL Standard Deviation 56.57	46.6 ng/mL Standard Deviation 50.89	44.6 ng/mL Standard Deviation 53.13	52.0 ng/mL Standard Deviation 27.94
Mean Predose Concentrations (Ctrough) of Inotuzumab Ozogamicin C3D1	21.4 ng/mL Standard Deviation 18.46	13.2 ng/mL Standard Deviation 7.93	17.3 ng/mL Standard Deviation 14.09	27.5 ng/mL Standard Deviation 14.64
Mean Predose Concentrations (Ctrough) of Inotuzumab Ozogamicin C3D8	31.9 ng/mL Standard Deviation 25.43	32.9 ng/mL Standard Deviation 12.96	32.5 ng/mL Standard Deviation 18.52	60.7 ng/mL Standard Deviation 44.89
Mean Predose Concentrations (Ctrough) of Inotuzumab Ozogamicin C4D1	50.0 ng/mL Standard Deviation 14.64	25.5 ng/mL Standard Deviation 2.33	37.7 ng/mL Standard Deviation 16.53	—
Mean Predose Concentrations (Ctrough) of Inotuzumab Ozogamicin C4D8	48.7 ng/mL Standard Deviation 7.99	52.3 ng/mL Standard Deviation 9.56	50.8 ng/mL Standard Deviation 8.10	90.4 ng/mL Standard Deviation NA Standard deviation was not applicable when there was only 1 participant analyzed.

SECONDARY outcome

Timeframe: At Day 1 of every cycle prior to the beginning of inotuzumab ozogamicin infusion and at the EOT visit, up to approximately 52 weeks.

Population: Participants who received at least 1 dose of study drug and had at least 1 ADA sample collected and analyzed for immunogenicity.

ADA incidence is defined as combined results of treatment-boosted and treatment-induced ADA-positive participants. The immunogenicity of inotuzumab ozogamicin was evaluated using a validated electrochemiluminescence (ECL)-based immunoassay.

Outcome measures

Outcome measures
Measure	1.2 mg/m²/Cycle (Dose Level 2 Run-in) n=22 Participants Participants received a starting dose of inotuzumab ozogamicin 1.2 mg/m²/cycle administrated in 3 divided doses (0.6 mg/m² on Day1, 0.3 mg/m² on Days 8 and 15) intravenously. After complete response (CR)/complete remission with incomplete hematologic recovery (CRi) was achieved, the dose was reduced to 0.9 mg/m²/cycle (0.3 mg/m² on Days 1, 8 and 15). The cycle length was 21-28 days. The maximum treatment duration was approximately 52 weeks.	1.2 mg/m²/Cycle (Dose Level 2 Randomized) n=41 Participants Participants received a starting dose of inotuzumab ozogamicin 1.2 mg/m²/cycle (0.6 mg/m² on Day 1, 0.3 mg/m² on Day 8 and 15) intravenously. After CR/CRi is achieved, the dose was reduced to 0.9 mg/m²/cycle (0.3 mg/m² on Day 1, 8 and 15) for 2-3 cycles. The cycle length was 21-28 days. The maximum treatment duration was approximately 52 weeks.	1.2 mg/m²/Cycle (Dose Level 2 Run-in + Randomized) n=63 Participants Participants received a starting dose of inotuzumab ozogamicin 1.2 mg/m²/cycle (0.6 mg/m² on Day 1, 0.3 mg/m² on Days 8 and 15) intravenously. After complete remission (CR)/complete remission with incomplete hematologic recovery (CRi) is achieved, the dose was reduced to 0.9 mg/m²/cycle (0.3 mg/m² on Day 1, 8 and 15). The maximum treatment duration was approximately 52 weeks.	1.8 mg/m²/Cycle (Dose Level 1 Randomized) n=38 Participants Participants received a starting dose of inotuzumab ozogamicin 1.8 mg/m²/cycle (0.8 mg/m² on Day 1, 0.5 mg/m² on Day 8 and 15) intravenously. After CR/CRi is achieved, the dose was reduced to 1.5 mg/m²/cycle (0.5 mg/m² on Day 1, 8 and 15) for 2-3 cycles. The cycle length was 21-28 days. The maximum treatment duration was approximately 52 weeks.
Number of Participants With Positive Anti-Drug Antibody (ADA) Positive Predose ADA	1 Participants	3 Participants	4 Participants	2 Participants
Number of Participants With Positive Anti-Drug Antibody (ADA) Treatment-induced ADA	1 Participants	0 Participants	1 Participants	1 Participants
Number of Participants With Positive Anti-Drug Antibody (ADA) Treatment-boosted ADA	0 Participants	0 Participants	0 Participants	0 Participants

SECONDARY outcome

Timeframe: At Day 1 of every cycle prior to the beginning of inotuzumab ozogamicin infusion and at the EOT visit, up to approximately 52 weeks.

Population: Participants who received at least 1 dose of study drug and had at least 1 Nab sample collected and analyzed for immunogenicity.

NAb incidence is defined as combined results of treatment-boosted and treatment-induced NAb-positive participants. The immunogenicity of inotuzumab ozogamicin was evaluated using a validated electrochemiluminescence (ECL)-based immunoassay.

Outcome measures

Outcome measures
Measure	1.2 mg/m²/Cycle (Dose Level 2 Run-in) n=2 Participants Participants received a starting dose of inotuzumab ozogamicin 1.2 mg/m²/cycle administrated in 3 divided doses (0.6 mg/m² on Day1, 0.3 mg/m² on Days 8 and 15) intravenously. After complete response (CR)/complete remission with incomplete hematologic recovery (CRi) was achieved, the dose was reduced to 0.9 mg/m²/cycle (0.3 mg/m² on Days 1, 8 and 15). The cycle length was 21-28 days. The maximum treatment duration was approximately 52 weeks.	1.2 mg/m²/Cycle (Dose Level 2 Randomized) n=3 Participants Participants received a starting dose of inotuzumab ozogamicin 1.2 mg/m²/cycle (0.6 mg/m² on Day 1, 0.3 mg/m² on Day 8 and 15) intravenously. After CR/CRi is achieved, the dose was reduced to 0.9 mg/m²/cycle (0.3 mg/m² on Day 1, 8 and 15) for 2-3 cycles. The cycle length was 21-28 days. The maximum treatment duration was approximately 52 weeks.	1.2 mg/m²/Cycle (Dose Level 2 Run-in + Randomized) n=5 Participants Participants received a starting dose of inotuzumab ozogamicin 1.2 mg/m²/cycle (0.6 mg/m² on Day 1, 0.3 mg/m² on Days 8 and 15) intravenously. After complete remission (CR)/complete remission with incomplete hematologic recovery (CRi) is achieved, the dose was reduced to 0.9 mg/m²/cycle (0.3 mg/m² on Day 1, 8 and 15). The maximum treatment duration was approximately 52 weeks.	1.8 mg/m²/Cycle (Dose Level 1 Randomized) n=3 Participants Participants received a starting dose of inotuzumab ozogamicin 1.8 mg/m²/cycle (0.8 mg/m² on Day 1, 0.5 mg/m² on Day 8 and 15) intravenously. After CR/CRi is achieved, the dose was reduced to 1.5 mg/m²/cycle (0.5 mg/m² on Day 1, 8 and 15) for 2-3 cycles. The cycle length was 21-28 days. The maximum treatment duration was approximately 52 weeks.
Number of Participants With Positive Neutralizing Antibody (NAb) Positive Predose NAb	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Positive Neutralizing Antibody (NAb) Treatment-induced NAb	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Positive Neutralizing Antibody (NAb) Treatment-boosted NAb	0 Participants	0 Participants	0 Participants	0 Participants

Adverse Events

1.2 mg/m²/Cycle (Dose Level 2 Run-in)

Serious events: 15 serious events

Other events: 18 other events

Deaths: 16 deaths

1.2 mg/m²/Cycle (Dose Level 2 Randomized Phase)

Serious events: 28 serious events

Other events: 32 other events

Deaths: 23 deaths

1.2 mg/m²/Cycle (Dose Level 2 Run-in + Randomized)

Serious events: 43 serious events

Other events: 50 other events

Deaths: 39 deaths

1.8 mg/m²/Cycle (Dose Level 1 Randomized Phase)

Serious events: 21 serious events

Other events: 29 other events

Deaths: 25 deaths

Serious adverse events

Other adverse events

Additional Information

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Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee Pfizer has the right to review disclosures, requesting a delay of less than 60 days. Investigator will postpone single center publications until after disclosure of pooled data (all sites), less than 12 months from study completion/termination at all participating sites. Investigator may not disclose previously undisclosed confidential information other than study results.
Publication restrictions are in place

Restriction type: OTHER