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Clinical Trial Results:
A Phase 4, Open-Label, Randomized Study of two Inotuzumab Ozogamicin Dose Levels In Adult Participants With Relapsed Or Refractory B-Cell Acute Lymphoblastic Leukemia Eligible for Hematopoietic Stem Cell Transplantation and who Have Risk Factor(S) for Veno-Occlusive Disease

Summary
EudraCT number	2018-001557-27
Trial protocol	PL BE HU ES
Global end of trial date	26 May 2023

Results information
Results version number	v1(current)
This version publication date	08 Jun 2024
First version publication date	08 Jun 2024
Other versions

Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information

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Trial information

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Sponsor protocol code

B1931030

ISRCTN number

US NCT number

NCT03677596

WHO universal trial number (UTN)

Sponsor organisation name

Pfizer Inc.

Sponsor organisation address

235 E 42nd Street, New York, United States, NY 10017

Public contact

Pfizer ClinicalTrials.gov Call Center, Pfizer Inc., 001 8007181021, ClinicalTrials.gov_Inquiries@pfizer.com

Scientific contact

Pfizer ClinicalTrials.gov Call Center, Pfizer Inc., 001 8007181021, ClinicalTrials.gov_Inquiries@pfizer.com

Is trial part of an agreed paediatric investigation plan (PIP)

Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?

Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?

Analysis stage

Final

Date of interim/final analysis

27 Nov 2023

Is this the analysis of the primary completion data?

Global end of trial reached?

Yes

Global end of trial date

26 May 2023

Was the trial ended prematurely?

Main objective of the trial

To evaluate the rates of veno-occlusive disease (VOD) and hematologic remission (complete remission/complete remission with incomplete hematologic recovery [CR/Cri]) for 2 Inotuzumab Ozogamicin dose levels in adult subjects with relapsed or refractory B-cell Acute lymphocytic leukemia (ALL) who are eligible for hematopoietic stem cell transplant (HSCT) and who are at higher risk for developing VOD post-HSCT.

Protection of trial subjects

The study was in compliance with the ethical principles derived from the Declaration of Helsinki and in compliance with all International Council for Harmonization (ICH) Good Clinical Practice (GCP) Guidelines. All the local regulatory requirements pertinent to safety of trials subjects were followed.

Background therapy

Evidence for comparator

Actual start date of recruitment

01 Jul 2019

Long term follow-up planned

Yes

Long term follow-up rationale

Safety

Long term follow-up duration

2 Years

Independent data monitoring committee (IDMC) involvement?

Yes

Number of subjects enrolled per country

Country: Number of subjects enrolled

Hungary: 1

Country: Number of subjects enrolled

Spain: 17

Country: Number of subjects enrolled

India: 14

Country: Number of subjects enrolled

Poland: 13

Country: Number of subjects enrolled

Singapore: 5

Country: Number of subjects enrolled

Türkiye: 43

Country: Number of subjects enrolled

Taiwan: 4

Country: Number of subjects enrolled

United States: 5

Worldwide total number of subjects

102

EEA total number of subjects

Number of subjects enrolled per age group

In utero

Preterm newborn - gestational age < 37 wk

Newborns (0-27 days)

Infants and toddlers (28 days-23 months)

Children (2-11 years)

Adolescents (12-17 years)

Adults (18-64 years)

From 65 to 84 years

85 years and over

Subject disposition

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Recruitment details

Screening details

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

Period 1 title

Overall Study (overall period)

Is this the baseline period?

Yes

Allocation method

Randomised - controlled

Blinding used

Not blinded

Are arms mutually exclusive

Yes

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

Arm description

Subjects 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 26 weeks.

Arm type

Experimental

Investigational medicinal product name

Inotuzumab Ozogamicin

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Intravenous use

Dosage and administration details

1.2 mg/m²/cycle administered in 3 divided doses (0.6 mg/m² on Day 1, 0.3 mg/m² on Days 8 and 15) intravenously.

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

Arm description

Subjects 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 26 weeks.

Arm type

Experimental

Investigational medicinal product name

Inotuzumab Ozogamicin

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Intravenous use

Dosage and administration details

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.

Number of subjects in period 1	1.2 mg/m²/cycle (Dose Level 2 Run-in + Randomized)	1.8 mg/m²/cycle (Dose Level 1 Randomized Phase)
Started	64	38
Completed	41	19
Not completed	23	19
Adverse event, serious fatal	10	6
Consent withdrawn by subject	3	-
Disease Relapse	2	2
Adverse event, non-fatal	-	1
Progressive Disease	8	8
Unspecified	-	1
Lost to follow-up	-	1

Baseline characteristics

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Reporting group title

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

Reporting group description

Reporting group title

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

Reporting group description

Reporting group values	1.2 mg/m²/cycle (Dose Level 2 Run-in + Randomized)	1.8 mg/m²/cycle (Dose Level 1 Randomized Phase)	Total
Number of subjects	64	38	102
Age Categorical
Units: Subjects
<=18 years	0	0	0
Between 18 and 65 years	59	36	95
>=65 years	5	2	7
Age continuous
Units: years
arithmetic mean (standard deviation)	43.27 ( 14.85 )	39.47 ( 15.26 )	-
Sex: Female, Male
Units: Subjects
Female	28	18	46
Male	36	20	56
Race (NIH/OMB)
Units: Subjects
American Indian or Alaska Native	0	0	0
Asian	11	11	22
Native Hawaiian or Other Pacific Islander	0	0	0
Black or African American	0	0	0
White	51	25	76
More than one race	0	0	0
Unknown or Not Reported	2	2	4
Ethnicity (NIH/OMB)
Units: Subjects
Hispanic or Latino	7	3	10
Not Hispanic or Latino	56	35	91
Unknown or Not Reported	1	0	1
ECOG Performance Status
Eastern Cooperative Oncology Group (ECOG) Performance Status is defined as: ECOG=0: Fully active, able to carry on all predisease performance without restriction; ECOG=1: Restricted in physically strenuous activity, but ambulatory and able to carry out work of a light or sedentary nature, ie, light house work, office work; ECOG=2: Ambulatory and capable of all self-care but unable to carry out any work activities. Up and about more than 50% of waking hours.
Units: Subjects
ECOG = 0	28	20	48
ECOG = 1	33	13	46
ECOG = 2	3	5	8
Body Mass Index (BMI)
BMI (kg/m^2) was computed as Height (cm)/Weight (kg) x 100.
Units: kg/m^2
median (full range (min-max))	25.26 (16 to 39)	24.78 (16 to 41)	-
Body Surface Area (BSA)
BSA (m^2) will be computed using Du Bois Formula: 0.007184 x Weight (kg)^0.425 x Height (cm)^0.725.
Units: m^2
median (full range (min-max))	1.84 (1 to 3)	1.79 (1 to 3)	-

Subject analysis set title

1.2 mg/m²/cycle (Dose Level 2 Run-in)

Subject analysis set type

Safety analysis

Subject analysis set description

Subjects 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 26 weeks.

Subject analysis set title

1.2 mg/m²/cycle (Dose Level 2 Randomised Phase)

Subject analysis set type

Safety analysis

Subject analysis set description

Subjects 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 26 weeks.

Subject analysis set title

1.2 mg/m²/cycle (Dose Level 2 Randomised)

Subject analysis set type

Safety analysis

Subject analysis set description

Subjects 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 26 weeks.

Subject analysis set title

1.8 mg/m²/cycle (Dose Level 1 Randomised)

Subject analysis set type

Safety analysis

Subject analysis set description

Subjects 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 26 weeks.

Subject analysis set title

1.2 mg/m²/cycle (Dose Level 2 Run-in)

Subject analysis set type

Safety analysis

Subject analysis set description

Subject analysis set title

1.2 mg/m²/cycle (Dose Level 2 Randomised)

Subject analysis set type

Safety analysis

Subject analysis set description

Subject analysis set title

1.8 mg/m²/cycle (Dose Level 1 Randomised)

Subject analysis set type

Safety analysis

Subject analysis set description

Subject analysis set title

1.2 mg/m²/cycle (Dose Level 2 Run-in)

Subject analysis set type

Safety analysis

Subject analysis set description

Subject analysis set title

1.2 mg/m²/cycle (Dose Level 2 Run-in)

Subject analysis set type

Safety analysis

Subject analysis set description

Subject analysis set title

1.2 mg/m²/cycle (Dose Level 2 Randomized)

Subject analysis set type

Safety analysis

Subject analysis set description

Subject analysis set title

1.8 mg/m²/cycle (Dose Level 1 Randomised)

Subject analysis set type

Safety analysis

Subject analysis set description

Subject analysis set title

1.2 mg/m²/cycle (Dose Level 2 Randomized)

Subject analysis set type

Safety analysis

Subject analysis set description

Subject analysis set title

1.2 mg/m²/cycle (Dose Level 2 Run-in)

Subject analysis set type

Safety analysis

Subject analysis set description

Subject analysis set title

1.2 mg/m²/cycle (Dose Level 2 Randomised)

Subject analysis set type

Safety analysis

Subject analysis set description

Subject analysis set title

1.8 mg/m²/cycle (Dose Level 1 Randomised)

Subject analysis set type

Safety analysis

Subject analysis set description

1.2 mg/m²/cycle (Dose Level 2 Run-in)

1.2 mg/m²/cycle (Dose Level 2 Randomised Phase)

1.2 mg/m²/cycle (Dose Level 2 Randomised)

1.8 mg/m²/cycle (Dose Level 1 Randomised)

1.2 mg/m²/cycle (Dose Level 2 Run-in)

1.2 mg/m²/cycle (Dose Level 2 Randomised)

1.8 mg/m²/cycle (Dose Level 1 Randomised)

1.2 mg/m²/cycle (Dose Level 2 Run-in)

1.2 mg/m²/cycle (Dose Level 2 Randomized)

1.8 mg/m²/cycle (Dose Level 1 Randomised)

1.2 mg/m²/cycle (Dose Level 2 Randomized)

1.2 mg/m²/cycle (Dose Level 2 Run-in)

1.2 mg/m²/cycle (Dose Level 2 Randomised)

1.8 mg/m²/cycle (Dose Level 1 Randomised)

Number of subjects

Units: Subjects

<=18 years

Between 18 and 65 years

>=65 years

Units: years

arithmetic mean (standard deviation)

( )

Units: Subjects

Female

Male

Units: Subjects

American Indian or Alaska Native

Asian

Native Hawaiian or Other Pacific Islander

Black or African American

White

More than one race

Unknown or Not Reported

Units: Subjects

Hispanic or Latino

Not Hispanic or Latino

Unknown or Not Reported

Eastern Cooperative Oncology Group (ECOG) Performance Status is defined as: ECOG=0: Fully active, able to carry on all predisease performance without restriction; ECOG=1: Restricted in physically strenuous activity, but ambulatory and able to carry out work of a light or sedentary nature, ie, light house work, office work; ECOG=2: Ambulatory and capable of all self-care but unable to carry out any work activities. Up and about more than 50% of waking hours.

Units: Subjects

ECOG = 0

ECOG = 1

ECOG = 2

BMI (kg/m^2) was computed as Height (cm)/Weight (kg) x 100.

Units: kg/m^2

median (full range (min-max))

BSA (m^2) will be computed using Du Bois Formula: 0.007184 x Weight (kg)^0.425 x Height (cm)^0.725.

Units: m^2

median (full range (min-max))

18 ( to )

End points

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Reporting group title

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

Reporting group description

Reporting group title

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

Reporting group description

Subject analysis set title

1.2 mg/m²/cycle (Dose Level 2 Run-in)

Subject analysis set type

Safety analysis

Subject analysis set description

Subject analysis set title

1.2 mg/m²/cycle (Dose Level 2 Randomised Phase)

Subject analysis set type

Safety analysis

Subject analysis set description

Subject analysis set title

1.2 mg/m²/cycle (Dose Level 2 Randomised)

Subject analysis set type

Safety analysis

Subject analysis set description

Subject analysis set title

1.8 mg/m²/cycle (Dose Level 1 Randomised)

Subject analysis set type

Safety analysis

Subject analysis set description

Subject analysis set title

1.2 mg/m²/cycle (Dose Level 2 Run-in)

Subject analysis set type

Safety analysis

Subject analysis set description

Subject analysis set title

1.2 mg/m²/cycle (Dose Level 2 Randomised)

Subject analysis set type

Safety analysis

Subject analysis set description

Subject analysis set title

1.8 mg/m²/cycle (Dose Level 1 Randomised)

Subject analysis set type

Safety analysis

Subject analysis set description

Subject analysis set title

1.2 mg/m²/cycle (Dose Level 2 Run-in)

Subject analysis set type

Safety analysis

Subject analysis set description

Subject analysis set title

1.2 mg/m²/cycle (Dose Level 2 Run-in)

Subject analysis set type

Safety analysis

Subject analysis set description

Subject analysis set title

1.2 mg/m²/cycle (Dose Level 2 Randomized)

Subject analysis set type

Safety analysis

Subject analysis set description

Subject analysis set title

1.8 mg/m²/cycle (Dose Level 1 Randomised)

Subject analysis set type

Safety analysis

Subject analysis set description

Subject analysis set title

1.2 mg/m²/cycle (Dose Level 2 Randomized)

Subject analysis set type

Safety analysis

Subject analysis set description

Subject analysis set title

1.2 mg/m²/cycle (Dose Level 2 Run-in)

Subject analysis set type

Safety analysis

Subject analysis set description

Subject analysis set title

1.2 mg/m²/cycle (Dose Level 2 Randomised)

Subject analysis set type

Safety analysis

Subject analysis set description

Subject analysis set title

1.8 mg/m²/cycle (Dose Level 1 Randomised)

Subject analysis set type

Safety analysis

Subject analysis set description

Primary: Percentage of Subjects With Veno-occlusive Disease (VOD)

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End point title

Percentage of Subjects With Veno-occlusive Disease (VOD) ^[1] ^[2]

End point description

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. All randomised subjects who received at least 1 dose of study drug.

End point type

Primary

End point timeframe

From consent up to follow-up (up to 2 years)

Notes
[1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: No statistical analysis was planned for this endpoint
[2] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Only descriptive analysis was planned for this endpoint.

End point values	1.2 mg/m²/cycle (Dose Level 2 Run-in + Randomized)	1.2 mg/m²/cycle (Dose Level 2 Run-in)	1.2 mg/m²/cycle (Dose Level 2 Randomised)	1.8 mg/m²/cycle (Dose Level 1 Randomised)
Number of subjects analysed	64	22	42	38
Units: Percentage of subjects
number (not applicable)	12.5	9.1	14.3	5.3

No statistical analyses for this end point

Primary: Rate of Hematologic Remission (Complete Response [CR] / Complete Response with Incomplete Hematologic Recovery[CRi])

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End point title

Rate of Hematologic Remission (Complete Response [CR] / Complete Response with Incomplete Hematologic Recovery[CRi]) ^[3] ^[4]

End point description

CR=disappearance of leukemia indicated by <5% marrow blasts, absence of peripheral blood leukemic blasts,recovery of hematopoiesis defined by absolute neutrophil count (ANC)>=1000/µL and platelets>=100000/µL. C1 extramedullary disease status is required. CRi = CR except with ANC <1000/µL and/or platelets <100000/µL. Subjects randomised into study with study drug assignment based on randomisation.

End point type

Primary

End point timeframe

From first dose of study treatment till follow-up of up to 2 years

Notes
[3] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: No statistical analysis was planned for this endpoint
[4] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Only descriptive analysis was planned for this endpoint.

End point values	1.2 mg/m²/cycle (Dose Level 2 Run-in + Randomized)	1.2 mg/m²/cycle (Dose Level 2 Run-in)	1.2 mg/m²/cycle (Dose Level 2 Randomised)	1.8 mg/m²/cycle (Dose Level 1 Randomised)
Number of subjects analysed	64	22	42	38
Units: Percentage of subjects
number (not applicable)	71.9	50.0	83.3	68.4

No statistical analyses for this end point

Secondary: Number of Subjects With Treatment-Emergent Adverse Events (Treatment-related)

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End point title

Number of Subjects With Treatment-Emergent Adverse Events (Treatment-related) ^[5]

End point description

Adverse event (AE) = any untoward medical occurrence in subject 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 hospitalisation; 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. All randomised subjects who received at least 1 dose of study drug.

End point type

Secondary

End point timeframe

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

Notes
[5] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Only descriptive analysis was planned for this endpoint.

End point values	1.2 mg/m²/cycle (Dose Level 2 Run-in + Randomized)	1.2 mg/m²/cycle (Dose Level 2 Run-in)	1.2 mg/m²/cycle (Dose Level 2 Randomised)	1.8 mg/m²/cycle (Dose Level 1 Randomised)
Number of subjects analysed	64	22	42	38
Units: Subjects
Participants with AEs	31	13	18	22
Participants with SAEs	15	7	8	10
Participants with Maximum Grade 3 or 4 AEs	20	9	11	11
Participants with Maximum Grade 5 AEs	2	1	1	4

No statistical analyses for this end point

Secondary: Number of Subjects With Treatment-Emergent Adverse Events (All Causalities)

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End point title

Number of Subjects With Treatment-Emergent Adverse Events (All Causalities) ^[6]

End point description

Adverse event (AE) = any untoward medical occurrence in subject 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 hospitalisation; 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. All randomised subjects who received at least 1 dose of study drug.

End point type

Secondary

End point timeframe

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

Notes
[6] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Only descriptive analysis was planned for this endpoint.

End point values	1.2 mg/m²/cycle (Dose Level 2 Run-in + Randomized)	1.2 mg/m²/cycle (Dose Level 2 Run-in)	1.2 mg/m²/cycle (Dose Level 2 Randomised)	1.8 mg/m²/cycle (Dose Level 1 Randomised)
Number of subjects analysed	64	22	42	38
Units: Subjects
Subjects with AE	60	21	39	35
Subjects with SAEs	43	15	28	21
Subjects with Maximum Grade 3 or 4 AE	30	9	21	18
Subjects with Maximum Grade 5 adverse events	19	7	12	10

No statistical analyses for this end point

Secondary: Number of Subjects With Treatment-Emergent Serious Adverse Events (Post-HSCT)

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End point title

Number of Subjects With Treatment-Emergent Serious Adverse Events (Post-HSCT) ^[7]

End point description

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 hospitalisation; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. All SAEs occurred after HSCT were reported in this endpoint. All randomised subjects who received at least 1 dose of study drug.

End point type

Secondary

End point timeframe

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

Notes
[7] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Only descriptive analysis was planned for this endpoint.

End point values	1.2 mg/m²/cycle (Dose Level 2 Run-in + Randomized)	1.2 mg/m²/cycle (Dose Level 2 Run-in)	1.2 mg/m²/cycle (Dose Level 2 Randomised Phase)	1.8 mg/m²/cycle (Dose Level 1 Randomised)
Number of subjects analysed	64	22	42	38
Units: Subjects	14	6	8	2

No statistical analyses for this end point

Secondary: Number of Subjects With Shift Summary of Hematology Laboratory Test Results from Grade Less Than or Equal to (<=) 2 at Baseline to Grade 3 or 4 Post-Baseline

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End point title

Number of Subjects With Shift Summary of Hematology Laboratory Test Results from Grade Less Than or Equal to (<=) 2 at Baseline to Grade 3 or 4 Post-Baseline ^[8]

End point description

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. All randomised subjects who received at least 1 dose of study drug and with at least 1 postbaseline assessment in each treatment group. ‘Number analysed’ = subjects evaluable for this endpoint for each specified row. ’99999’=Grade4 was not applicable for the test.

End point type

Secondary

End point timeframe

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

Notes
[8] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Only descriptive analysis was planned for this endpoint.

End point values	1.2 mg/m²/cycle (Dose Level 2 Run-in + Randomized)	1.2 mg/m²/cycle (Dose Level 2 Run-in)	1.2 mg/m²/cycle (Dose Level 2 Randomised)	1.8 mg/m²/cycle (Dose Level 1 Randomised)
Number of subjects analysed	64	22	42	38
Units: Subjects
APT time prolonged - Grade 3 (n=51,19,32,27)	0	0	0	0
APT time prolonged - Grade 4 (n=51,19,32,27)	99999	99999	99999	99999
Anemia - Grade 3 (n=37,15,22,20)	21	8	13	11
Anemia - Grade 4 (n=37,15,22,20)	99999	99999	99999	99999
Hemoglobin increased - Grade 3(n=18,6,12,13)	0	0	0	0
Hemoglobin increased - Grade 4(n=18,6,12,13)	99999	99999	99999	99999
INR increased - Grade 3(n=27,11,16,12)	0	0	0	0
INR increased - Grade 4(n=27,11,16,12)	99999	99999	99999	99999
Leukocytosis - Grade 3(n=18,7,11,13)	1	1	0	0
Leukocytosis - Grade 4(n=18,7,11,13)	99999	99999	99999	99999
Lymphocyte count decreased-Grade 3(n=51,16,35,28)	16	1	15	7
Lymphocyte count decreased-Grade 4(n=51,16,35,28)	6	4	2	4
Lymphocyte count increased-Grade 3(n=27,13,14,17)	3	2	1	3
Lymphocyte count increased-Grade 4(n=27,13,14,17)	99999	99999	99999	99999
Neutrophil count decreased-Grade 3(n=51,17,34,27)	8	2	6	7
Neutrophil count decreased-Grade 4(n=51,17,34,27)	21	11	10	9
Platelet count decreased-Grade 3(n=41,13,28,28)	7	1	6	5
Platelet count decreased - Grade 4(n=41,13,28,28)	7	4	3	7
White blood cell decreased-Grade 3(n=56,18,38,29)	18	5	13	9
White blood cell decreased-Grade 4(n=56,18,38,29)	17	7	10	11

No statistical analyses for this end point

Secondary: Number of Subjects With Shift Summary of Chemistry Laboratory Test Results from Grade <=2 at Baseline to Grade 3 or 4 Post-Baseline

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End point title

Number of Subjects With Shift Summary of Chemistry Laboratory Test Results from Grade <=2 at Baseline to Grade 3 or 4 Post-Baseline ^[9]

End point description

Baseline assessment=last assessment performed on or prior to date of first dose of study treatment. Parameters analysed for laboratory assessment:Chemistry(Alanine aminotransferase[ALT] increased,Alkaline phosphatase[ALP] increased,Aspartate aminotransferase[AST] 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,Serum amylase increased).Grades of severity defined by CTCAE v3.0.Grade 2=moderate AE ;Grade 3=severe AE ;Grade 4= life-threatening consequences; urgent intervention indicated. All randomised subjects who received at least 1 dose of study drug with at least 1 postbaseline assessment in each treatment group.‘Number analysed’= subjects evaluable for each specified row.’99999’=Grade4 was not applicable for the test.

End point type

Secondary

End point timeframe

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

Notes
[9] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Only descriptive analysis was planned for this endpoint.

End point values	1.2 mg/m²/cycle (Dose Level 2 Run-in + Randomized)	1.2 mg/m²/cycle (Dose Level 2 Run-in)	1.2 mg/m²/cycle (Dose Level 2 Randomised)	1.8 mg/m²/cycle (Dose Level 1 Randomised)
Number of subjects analysed	64	22	42	38
Units: Subjects
ALT increased - Grade 3 (n=29,14,15,23)	1	1	0	0
ALT increased - Grade 4(n=29,14,15,23)	0	0	0	0
ALP increased - Grade 3 (n=42,14,28,22)	1	1	0	1
ALP increased - Grade 4 (n=42,14,28,22)	0	0	0	0
AST increased - Grade 3(n=42,16,26,26)	4	1	3	0
AST increased - Grade 4(n=42,16,26,26)	0	0	0	0
Blood bilirubin increased - Grade 3(n=31,14,17,20)	2	1	1	0
Blood bilirubin increased - Grade 4(n=31,14,17,20)	0	0	0	0
Chronic kidney disease - Grade 3(n=9,2,7,7)	0	0	0	0
Chronic kidney disease - Grade 4(n=9,2,7,7)	0	0	0	0
Creatinine increased - Grade 3(n=50,19,31,26)	0	0	0	0
Creatinine increased - Grade 4(n=50,19,31,26)	0	0	0	0
GGT increased - Grade 3(n=37,15,22,26)	3	1	2	3
GGT increased - Grade 4(n=37,15,22,26)	0	0	0	0
Hypercalcemia - Grade 3(n=22,10,12,15)	0	0	0	0
Hypercalcemia - Grade 4(n=22,10,12,15)	0	0	0	0
Hyperglycemia - Grade 3(n=37,13,24,21)	4	2	2	2
Hyperglycemia - Grade 4(n=37,13,24,21)	0	0	0	0
Hyperkalemia - Grade 3(n=21,10,11,14)	0	0	0	0
Hyperkalemia - Grade 4(n=21,10,11,14)	1	1	0	0
Hypermagnesemia - Grade 3(n=21,11,10,15)	1	1	0	1
Hypermagnesemia - Grade 4(n=21,11,10,15)	0	0	0	0
Hypernatremia - Grade 3(n=19,9,10,15)	0	0	0	0
Hypernatremia - Grade 4(n=19,9,10,15)	1	0	1	0
Hypoalbuminemia - Grade 3 (n=31,16,15,21)	4	1	3	3
Hypoalbuminemia - Grade 4(n=31,16,15,21)	99999	99999	99999	99999
Hypocalcemia - Grade 3(n=28,12,16,15)	1	1	0	0
Hypocalcemia - Grade 4(n=28,12,16,15)	0	0	0	0
Hypoglycemia - Grade 3(n=22,10,12,16)	0	0	0	0
Hypoglycemia - Grade 4(n=22,10,12,16)	0	0	0	0
Hypokalemia - Grade 3(n=32,13,19,24)	3	1	2	1
Hypokalemia - Grade 4(n=32,13,19,24)	1	1	0	0
Hypomagnesemia - Grade 3(n=30,14,16,18)	1	1	0	1
Hypomagnesemia - Grade 4(n=30,14,16,18)	0	0	0	1
Hyponatremia - Grade 3(n=27,13,14,19)	1	1	0	0
Hyponatremia - Grade 4(n=27,13,14,19)	0	0	0	0
Hypophosphatemia- Grade 3(n=26,13,13,18)	2	2	0	1
Hypophosphatemia - Grade 4(n=26,13,13,18)	0	0	0	1
Lipase increased - Grade 3(n=38,15,23,24)	6	3	3	2
Lipase increased - Grade 4(n=38,15,23,24)	2	0	2	0
Serum amylase increased - Grade 3(n=32,14,18,22)	2	1	1	0
Serum amylase increased - Grade 4(n=32,14,18,22)	0	0	0	0

No statistical analyses for this end point

Secondary: Number of Subjects Achieving a CR/CRi with Minimal Residual Disease (MRD) Negativity

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End point title

Number of Subjects Achieving a CR/CRi with Minimal Residual Disease (MRD) Negativity ^[10]

End point description

Subjects who achieved CR/CRi, a patient was considered to be MRD negative if the minimum MRD (%) between the date of achieving CR/CRi and end of treatment test is <0.01%. All subjects who were randomised into the study and achieved CR/CRi.

End point type

Secondary

End point 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

Notes
[10] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Only descriptive analysis was planned for this endpoint.

End point values	1.2 mg/m²/cycle (Dose Level 2 Run-in + Randomized)	1.2 mg/m²/cycle (Dose Level 2 Run-in)	1.2 mg/m²/cycle (Dose Level 2 Randomised Phase)	1.8 mg/m²/cycle (Dose Level 1 Randomised)
Number of subjects analysed	46	11	35	26
Units: Subjects	33	8	25	18

No statistical analyses for this end point

Secondary: Duration of Remission (DoR) in Subjects who Achieved CR/CRi

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End point title

Duration of Remission (DoR) in Subjects who Achieved CR/CRi ^[11]

End point description

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. 99999 indicates upper limit was not estimated due to fewer number of subjects with event. Subjects who were randomised into the study and with a remission (CR/CRi).

End point type

Secondary

End point timeframe

From date of first response (subjects who achieved CR/CRi) to the date of disease progression or death due to any cause

Notes
[11] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Only descriptive analysis was planned for this endpoint.

End point values	1.2 mg/m²/cycle (Dose Level 2 Run-in + Randomized)	1.2 mg/m²/cycle (Dose Level 2 Run-in)	1.2 mg/m²/cycle (Dose Level 2 Randomised Phase)	1.8 mg/m²/cycle (Dose Level 1 Randomised)
Number of subjects analysed	46	11	35	26
Units: Months
median (confidence interval 95%)	5.5 (4.7 to 13.4)	5.2 (1.9 to 99999)	6.5 (4.6 to 20.9)	6.8 (4.7 to 8.7)

No statistical analyses for this end point

Secondary: Number of Subjects who Received HSCT Post Inotuzumab Ozogamicin Treatment

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End point title

Number of Subjects who Received HSCT Post Inotuzumab Ozogamicin Treatment ^[12]

End point description

Subjects who underwent HSCT after inotuzumab ozogamicin treatment. All subjects who were randomised into the study with study drug assignment based on randomisation.

End point type

Secondary

End point timeframe

From first dose of study treatment till follow-up of up to 2 years

Notes
[12] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: No statistical analysis was planned for this endpoint

End point values	1.2 mg/m²/cycle (Dose Level 2 Run-in + Randomized)	1.2 mg/m²/cycle (Dose Level 2 Run-in)	1.2 mg/m²/cycle (Dose Level 2 Randomised)	1.8 mg/m²/cycle (Dose Level 1 Randomised)
Number of subjects analysed	64	22	42	38
Units: Subjects	31	10	21	12

No statistical analyses for this end point

Secondary: Overall Survival

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End point title

Overall Survival ^[13]

End point description

Overall survival was defined as the time from date of first dose of study treatment to death due to any cause. Subjects without confirmation of death were censored at the date that the subject was last known to be alive. 99999 indicates upper limit was not estimable due to fewer number of subjects with event. All subjects who were randomised into the study with study drug assignment based on randomisation.

End point type

Secondary

End point timeframe

From date of randomisation to death due to any cause

Notes
[13] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Only descriptive analysis was planned for this endpoint.

End point values	1.2 mg/m²/cycle (Dose Level 2 Run-in + Randomized)	1.2 mg/m²/cycle (Dose Level 2 Run-in)	1.2 mg/m²/cycle (Dose Level 2 Randomised)	1.8 mg/m²/cycle (Dose Level 1 Randomised)
Number of subjects analysed	64	22	42	38
Units: Months
median (confidence interval 95%)	7.6 (5.8 to 10.0)	4.5 (3.2 to 8.6)	9.6 (6.4 to 99999)	8.1 (5.4 to 10.4)

No statistical analyses for this end point

Secondary: Progression Free Survival (PFS)

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End point title

Progression Free Survival (PFS) ^[14]

End point description

PFS was defined as time from date of randomisation 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 occurred first. PFS was estimated using Kaplan-Meier methods. Results were reported as of the data cutoff date on 21 Sep 2022.All subjects who were randomised into the study with study drug assignment based on randomisation.

End point type

Secondary

End point timeframe

From date of randomisation to date of disease progression, death, or starting new induction therapy/post-therapy HSCT without achieving CR/Cri

Notes
[14] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Only descriptive analysis was planned for this endpoint.

End point values	1.2 mg/m²/cycle (Dose Level 2 Run-in + Randomized)	1.2 mg/m²/cycle (Dose Level 2 Run-in)	1.2 mg/m²/cycle (Dose Level 2 Randomised)	1.8 mg/m²/cycle (Dose Level 1 Randomised)
Number of subjects analysed	64	22	42	38
Units: Months
median (confidence interval 95%)	5.3 (3.4 to 7.2)	2.9 (1.7 to 5.8)	6.4 (4.8 to 16.0)	6.3 (2.8 to 8.0)

No statistical analyses for this end point

Secondary: Cumulative Incidence Rate of Post-HSCT Relapse at Month 12

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End point title

Cumulative Incidence Rate of Post-HSCT Relapse at Month 12 ^[15]

End point description

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. All subjects who were randomised into the study with study drug assignment based on randomisation and who were post HSCT.

End point type

Secondary

End point timeframe

From date of HSCT to the date of first relapse post-HSCT to Month 12

Notes
[15] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Only descriptive analysis was planned for this endpoint.

End point values	1.2 mg/m²/cycle (Dose Level 2 Run-in + Randomized)	1.2 mg/m²/cycle (Dose Level 2 Run-in)	1.2 mg/m²/cycle (Dose Level 2 Randomised)	1.8 mg/m²/cycle (Dose Level 1 Randomised)
Number of subjects analysed	31	10	21	12
Units: Percentages of subjects
number (confidence interval 95%)	17.58 (6.17 to 33.79)	11.11 (0.40 to 41.66)	20.51 (6.00 to 40.97)	16.67 (2.26 to 42.89)

No statistical analyses for this end point

Secondary: Number of Subjects With Post-HSCT Mortality

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End point title

Number of Subjects With Post-HSCT Mortality ^[16]

End point description

Post-HSCT Mortality was defined as the time from date of first HSCT after inotuzumab ozogamicin treatment to death due to any cause. All subjects who were randomised into the study with study drug assignment based on randomisation and who were post HSCT.

End point type

Secondary

End point timeframe

From date of HSCT to the date of death due to any cause (approximately 4 years)

Notes
[16] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Only descriptive analysis was planned for this endpoint.

End point values	1.2 mg/m²/cycle (Dose Level 2 Run-in + Randomized)	1.2 mg/m²/cycle (Dose Level 2 Run-in)	1.2 mg/m²/cycle (Dose Level 2 Randomised Phase)	1.8 mg/m²/cycle (Dose Level 1 Randomised)
Number of subjects analysed	31	10	21	12
Units: Subjects	14	6	8	6

No statistical analyses for this end point

Secondary: Number of Subjects With Post HSCT non-Relapse Mortality

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End point title

Number of Subjects With Post HSCT non-Relapse Mortality ^[17]

End point description

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. All subjects who were randomised into the study with study drug assignment based on randomisation and who underwent HSCT after inotuzumab ozogamicin treatment.

End point type

Secondary

End point timeframe

From date of HSCT to the date of death due to any cause without prior relapse/progression post-HSCT (approximately 4 years)

Notes
[17] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Only descriptive analysis was planned for this endpoint.

End point values	1.2 mg/m²/cycle (Dose Level 2 Run-in + Randomized)	1.2 mg/m²/cycle (Dose Level 2 Run-in)	1.2 mg/m²/cycle (Dose Level 2 Randomised Phase)	1.2 mg/m²/cycle (Dose Level 2 Randomised)
Number of subjects analysed	31	10	21	12
Units: Subjects	10	5	5	4

No statistical analyses for this end point

Secondary: Number of Subjects with Post HSCT Relapse-Related Mortality

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End point title

Number of Subjects with Post HSCT Relapse-Related Mortality ^[18]

End point description

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. All subjects who were randomised into the study with study drug assignment based on randomisation and who underwent HSCT after inotuzumab ozogamicin treatment.

End point type

Secondary

End point timeframe

From date of HSCT to the date of death due to any cause with prior relapse/progression post-HSCT (approximately 4 years)

Notes
[18] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Only descriptive analysis was planned for this endpoint.

End point values	1.2 mg/m²/cycle (Dose Level 2 Run-in + Randomized)	1.2 mg/m²/cycle (Dose Level 2 Run-in)	1.2 mg/m²/cycle (Dose Level 2 Randomised Phase)	1.2 mg/m²/cycle (Dose Level 2 Randomised)
Number of subjects analysed	31	10	21	12
Units: Subjects	4	1	3	2

No statistical analyses for this end point

Secondary: Mean Predose Concentrations (Ctrough) of Inotuzumab Ozogamicin

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End point title

Mean Predose Concentrations (Ctrough) of Inotuzumab Ozogamicin ^[19]

End point description

Ctrough was defined as the mean Predose concentration of study treatment. All treated subjects who received at least 1 dose of study drug and had at least one PK sample collected and analysed. ‘Number analysed’ = Subjects evaluable for this endpoint for each specified row.

End point type

Secondary

End point timeframe

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

Notes
[19] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Only descriptive analysis was planned for this endpoint.

End point values	1.2 mg/m²/cycle (Dose Level 2 Run-in + Randomized)	1.2 mg/m²/cycle (Dose Level 2 Run-in)	1.2 mg/m²/cycle (Dose Level 2 Randomised)	1.8 mg/m²/cycle (Dose Level 1 Randomised)
Number of subjects analysed	64	22	42	38
Units: Nanogram per milliliter
arithmetic mean (standard deviation)
Cycle 1 Day 1 (C1D1) n=61,22,39,37	0.8 ( 5.56 )	1.9 ( 9.10 )	0.2 ( 1.38 )	0.1 ( 0.35 )
C1D8 (n=60,22,38,36)	8.1 ( 21.24 )	7.7 ( 20.53 )	8.3 ( 21.91 )	4.3 ( 6.05 )
C1D15 (n=60,21,39,33)	15.8 ( 31.34 )	8.9 ( 11.14 )	19.5 ( 37.67 )	25.8 ( 32.89 )
C2D1 (n=54,17,37,24)	15.6 ( 24.95 )	16.4 ( 21.43 )	15.2 ( 26.67 )	22.0 ( 47.15 )
C2D8 (n=51,18,33,22)	42.7 ( 46.93 )	42.6 ( 56.57 )	42.8 ( 41.73 )	48.6 ( 24.99 )
C3D1 (n=17,5,12,11)	30.2 ( 43.39 )	21.4 ( 18.46 )	33.9 ( 50.64 )	37.1 ( 34.03 )
C3D8 (n=19,5,14,9)	36.2 ( 18.20 )	31.9 ( 25.43 )	37.8 ( 15.82 )	68.8 ( 39.22 )
C4D1 (n=6,2,4,0)	29.4 ( 18.12 )	50.0 ( 14.64 )	19.2 ( 7.42 )	99999 ( 99999 )
C4D8 (n=6,2,4,1	47.7 ( 10.63 )	48.7 ( 7.99 )	47.2 ( 12.88 )	90.4 ( 99999 )

No statistical analyses for this end point

Secondary: Number of Subjects With Positive Anti-Drug Antibody (ADA)

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End point title

Number of Subjects With Positive Anti-Drug Antibody (ADA) ^[20]

End point description

ADA incidence is defined as combined results of treatment-boosted and treatment-induced ADA-positive subjects. The immunogenicity of inotuzumab ozogamicin was evaluated using a validated electrochemiluminescence (ECL)-based immunoassay. Subjects who received at least 1 dose of study drug and had at least 1 ADA sample collected and analysed for immunogenicity.

End point type

Secondary

End point timeframe

At Day 1 of every cycle prior to the beginning of inotuzumab ozogamicin infusion and at the EOT visit, up to approximately 4 years

Notes
[20] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Only descriptive analysis was planned for this endpoint.

End point values	1.2 mg/m²/cycle (Dose Level 2 Run-in + Randomized)	1.2 mg/m²/cycle (Dose Level 2 Run-in)	1.8 mg/m²/cycle (Dose Level 1 Randomised)	1.2 mg/m²/cycle (Dose Level 2 Randomized)
Number of subjects analysed	63	22	38	41
Units: Subjects
Positive Predose ADA	4	1	2	3
Treatment-induced ADA	1	1	1	0
Treatment-boosted ADA	0	0	0	0

No statistical analyses for this end point

Secondary: Number of Subjects With Positive Neutralizing Antibody (NAb)

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End point title

Number of Subjects With Positive Neutralizing Antibody (NAb) ^[21]

End point description

NAb incidence is defined as combined results of treatment-boosted and treatment-induced NAb-positive subjects. The immunogenicity of inotuzumab ozogamicin was evaluated using a validated electrochemiluminescence (ECL)-based immunoassay. Subjects who received at least 1 dose of study drug and had at least 1 Nab sample collected and analysed for immunogenicity.

End point type

Secondary

End point timeframe

At Day 1 of every cycle prior to the beginning of inotuzumab ozogamicin infusion and at the EOT visit, up to approximately 4 years.

Notes
[21] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Only descriptive analysis was planned for this endpoint.

End point values	1.2 mg/m²/cycle (Dose Level 2 Run-in + Randomized)	1.2 mg/m²/cycle (Dose Level 2 Run-in)	1.2 mg/m²/cycle (Dose Level 2 Randomised Phase)	1.8 mg/m²/cycle (Dose Level 1 Randomised)
Number of subjects analysed	5	2	3	3
Units: Subjects
Positive Predose NAb	0	0	0	0
Treatment-induced NAb	0	0	0	0
Treatment-boosted NAb	0	0	0	0

No statistical analyses for this end point

Adverse events

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Timeframe for reporting adverse events

From the time of consent including a minimum of 9 weeks after the last dose

Adverse event reporting additional description

Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event. Analysis performed on safety set.

Assessment type

Non-systematic

Dictionary name

MedDRA

Dictionary version

26.0

Reporting group title

1.2 mg/m2/cycle (Run-in)

Reporting group description

Reporting group title

1.8 mg/m2/cycle (Randomized)

Reporting group description

Reporting group title

1.2 mg/m2/cycle (Run-in + Randomized)

Reporting group description

Subjects received a starting dose of inotuzumab ozogamicin 1.2 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 4 years.

Reporting group title

1.2 mg/m2/cycle (Randomized)

Reporting group description

Serious adverse events	1.2 mg/m2/cycle (Run-in)	1.8 mg/m2/cycle (Randomized)	1.2 mg/m2/cycle (Run-in + Randomized)	1.2 mg/m2/cycle (Randomized)
Total subjects affected by serious adverse events
subjects affected / exposed	15 / 22 (68.18%)	21 / 38 (55.26%)	43 / 64 (67.19%)	28 / 42 (66.67%)
number of deaths (all causes)	16	26	40	24
number of deaths resulting from adverse events	7	10	19	12
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Neoplasm recurrence
subjects affected / exposed	0 / 22 (0.00%)	1 / 38 (2.63%)	0 / 64 (0.00%)	0 / 42 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 2	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
Neoplasm progression
subjects affected / exposed	0 / 22 (0.00%)	2 / 38 (5.26%)	0 / 64 (0.00%)	0 / 42 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 3	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 2	0 / 0	0 / 0
Myelodysplastic syndrome
subjects affected / exposed	1 / 22 (4.55%)	0 / 38 (0.00%)	1 / 64 (1.56%)	0 / 42 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
General disorders and administration site conditions
Disease progression
subjects affected / exposed	3 / 22 (13.64%)	2 / 38 (5.26%)	4 / 64 (6.25%)	1 / 42 (2.38%)
occurrences causally related to treatment / all	0 / 3	2 / 4	0 / 4	0 / 1
deaths causally related to treatment / all	0 / 2	1 / 2	0 / 3	0 / 1
Pyrexia
subjects affected / exposed	1 / 22 (4.55%)	3 / 38 (7.89%)	3 / 64 (4.69%)	2 / 42 (4.76%)
occurrences causally related to treatment / all	0 / 1	2 / 3	2 / 3	2 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Death
subjects affected / exposed	0 / 22 (0.00%)	1 / 38 (2.63%)	1 / 64 (1.56%)	1 / 42 (2.38%)
occurrences causally related to treatment / all	0 / 0	1 / 1	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	1 / 1	0 / 1	0 / 1
Immune system disorders
Graft versus host disease in liver
subjects affected / exposed	0 / 22 (0.00%)	0 / 38 (0.00%)	1 / 64 (1.56%)	1 / 42 (2.38%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Respiratory, thoracic and mediastinal disorders
Sinus polyp
subjects affected / exposed	0 / 22 (0.00%)	0 / 38 (0.00%)	1 / 64 (1.56%)	1 / 42 (2.38%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Investigations
SARS-CoV-2 test positive
subjects affected / exposed	0 / 22 (0.00%)	1 / 38 (2.63%)	1 / 64 (1.56%)	1 / 42 (2.38%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Klebsiella test positive
subjects affected / exposed	1 / 22 (4.55%)	0 / 38 (0.00%)	1 / 64 (1.56%)	0 / 42 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Injury, poisoning and procedural complications
Subdural haematoma
subjects affected / exposed	0 / 22 (0.00%)	1 / 38 (2.63%)	0 / 64 (0.00%)	0 / 42 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Post procedural inflammation
subjects affected / exposed	0 / 22 (0.00%)	0 / 38 (0.00%)	1 / 64 (1.56%)	1 / 42 (2.38%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Fall
subjects affected / exposed	0 / 22 (0.00%)	1 / 38 (2.63%)	0 / 64 (0.00%)	0 / 42 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Cardiac disorders
Coronary artery thrombosis
subjects affected / exposed	0 / 22 (0.00%)	1 / 38 (2.63%)	0 / 64 (0.00%)	0 / 42 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
Nervous system disorders
Central nervous system lesion
subjects affected / exposed	0 / 22 (0.00%)	0 / 38 (0.00%)	1 / 64 (1.56%)	1 / 42 (2.38%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Focal dyscognitive seizures
subjects affected / exposed	1 / 22 (4.55%)	0 / 38 (0.00%)	1 / 64 (1.56%)	0 / 42 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Loss of consciousness
subjects affected / exposed	0 / 22 (0.00%)	1 / 38 (2.63%)	0 / 64 (0.00%)	0 / 42 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Haemorrhage intracranial
subjects affected / exposed	0 / 22 (0.00%)	2 / 38 (5.26%)	1 / 64 (1.56%)	1 / 42 (2.38%)
occurrences causally related to treatment / all	0 / 0	3 / 4	1 / 1	1 / 1
deaths causally related to treatment / all	0 / 0	1 / 1	0 / 0	0 / 0
Blood and lymphatic system disorders
Anaemia megaloblastic
subjects affected / exposed	1 / 22 (4.55%)	0 / 38 (0.00%)	1 / 64 (1.56%)	0 / 42 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Febrile neutropenia
subjects affected / exposed	3 / 22 (13.64%)	4 / 38 (10.53%)	7 / 64 (10.94%)	4 / 42 (9.52%)
occurrences causally related to treatment / all	4 / 4	4 / 6	7 / 8	3 / 4
deaths causally related to treatment / all	0 / 0	1 / 2	0 / 0	0 / 0
Thrombocytopenia
subjects affected / exposed	1 / 22 (4.55%)	0 / 38 (0.00%)	2 / 64 (3.13%)	1 / 42 (2.38%)
occurrences causally related to treatment / all	1 / 1	0 / 0	1 / 2	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Gastrointestinal disorders
Pancreatitis acute
subjects affected / exposed	0 / 22 (0.00%)	0 / 38 (0.00%)	1 / 64 (1.56%)	1 / 42 (2.38%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Gastrointestinal haemorrhage
subjects affected / exposed	0 / 22 (0.00%)	1 / 38 (2.63%)	0 / 64 (0.00%)	0 / 42 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Enterocolitis
subjects affected / exposed	0 / 22 (0.00%)	1 / 38 (2.63%)	0 / 64 (0.00%)	0 / 42 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Hepatobiliary disorders
Cholecystitis
subjects affected / exposed	0 / 22 (0.00%)	1 / 38 (2.63%)	0 / 64 (0.00%)	0 / 42 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Drug-induced liver injury
subjects affected / exposed	0 / 22 (0.00%)	1 / 38 (2.63%)	0 / 64 (0.00%)	0 / 42 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Venoocclusive liver disease
subjects affected / exposed	2 / 22 (9.09%)	2 / 38 (5.26%)	8 / 64 (12.50%)	6 / 42 (14.29%)
occurrences causally related to treatment / all	5 / 5	1 / 2	6 / 12	1 / 7
deaths causally related to treatment / all	1 / 1	0 / 0	1 / 2	0 / 1
Skin and subcutaneous tissue disorders
Dermatitis contact
subjects affected / exposed	0 / 22 (0.00%)	0 / 38 (0.00%)	1 / 64 (1.56%)	1 / 42 (2.38%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Infections and infestations
Bacteraemia
subjects affected / exposed	0 / 22 (0.00%)	0 / 38 (0.00%)	1 / 64 (1.56%)	1 / 42 (2.38%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 2	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 1
COVID-19
subjects affected / exposed	0 / 22 (0.00%)	1 / 38 (2.63%)	2 / 64 (3.13%)	2 / 42 (4.76%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 2	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
COVID-19 pneumonia
subjects affected / exposed	0 / 22 (0.00%)	0 / 38 (0.00%)	3 / 64 (4.69%)	3 / 42 (7.14%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 5	0 / 5
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 2	0 / 2
Hepatosplenic candidiasis
subjects affected / exposed	0 / 22 (0.00%)	0 / 38 (0.00%)	1 / 64 (1.56%)	1 / 42 (2.38%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Device related infection
subjects affected / exposed	0 / 22 (0.00%)	0 / 38 (0.00%)	1 / 64 (1.56%)	1 / 42 (2.38%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Escherichia infection
subjects affected / exposed	1 / 22 (4.55%)	0 / 38 (0.00%)	1 / 64 (1.56%)	0 / 42 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Fungal infection
subjects affected / exposed	2 / 22 (9.09%)	0 / 38 (0.00%)	2 / 64 (3.13%)	0 / 42 (0.00%)
occurrences causally related to treatment / all	1 / 2	0 / 0	1 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Fungal sepsis
subjects affected / exposed	1 / 22 (4.55%)	0 / 38 (0.00%)	1 / 64 (1.56%)	0 / 42 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 1	0 / 0	0 / 1	0 / 0
Cellulitis
subjects affected / exposed	0 / 22 (0.00%)	0 / 38 (0.00%)	1 / 64 (1.56%)	1 / 42 (2.38%)
occurrences causally related to treatment / all	0 / 0	0 / 0	1 / 1	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Neutropenic sepsis
subjects affected / exposed	0 / 22 (0.00%)	1 / 38 (2.63%)	0 / 64 (0.00%)	0 / 42 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Klebsiella sepsis
subjects affected / exposed	0 / 22 (0.00%)	0 / 38 (0.00%)	1 / 64 (1.56%)	1 / 42 (2.38%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 1
Infection
subjects affected / exposed	0 / 22 (0.00%)	1 / 38 (2.63%)	0 / 64 (0.00%)	0 / 42 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Pneumocystis jirovecii pneumonia
subjects affected / exposed	0 / 22 (0.00%)	0 / 38 (0.00%)	1 / 64 (1.56%)	1 / 42 (2.38%)
occurrences causally related to treatment / all	0 / 0	0 / 0	2 / 2	2 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	1 / 1	1 / 1
Septic shock
subjects affected / exposed	1 / 22 (4.55%)	0 / 38 (0.00%)	4 / 64 (6.25%)	3 / 42 (7.14%)
occurrences causally related to treatment / all	0 / 2	0 / 0	0 / 6	0 / 4
deaths causally related to treatment / all	0 / 1	0 / 0	0 / 3	0 / 2
Sepsis
subjects affected / exposed	2 / 22 (9.09%)	1 / 38 (2.63%)	6 / 64 (9.38%)	4 / 42 (9.52%)
occurrences causally related to treatment / all	0 / 3	2 / 2	0 / 8	0 / 5
deaths causally related to treatment / all	0 / 1	1 / 1	0 / 4	0 / 3
Pneumonia klebsiella
subjects affected / exposed	1 / 22 (4.55%)	0 / 38 (0.00%)	2 / 64 (3.13%)	1 / 42 (2.38%)
occurrences causally related to treatment / all	0 / 2	0 / 0	2 / 4	2 / 2
deaths causally related to treatment / all	0 / 1	0 / 0	1 / 2	1 / 1
Pneumonia fungal
subjects affected / exposed	0 / 22 (0.00%)	1 / 38 (2.63%)	0 / 64 (0.00%)	0 / 42 (0.00%)
occurrences causally related to treatment / all	0 / 0	2 / 2	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	1 / 1	0 / 0	0 / 0
Pneumonia bacterial
subjects affected / exposed	0 / 22 (0.00%)	1 / 38 (2.63%)	0 / 64 (0.00%)	0 / 42 (0.00%)
occurrences causally related to treatment / all	0 / 0	2 / 2	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	1 / 1	0 / 0	0 / 0
Pneumonia
subjects affected / exposed	1 / 22 (4.55%)	0 / 38 (0.00%)	1 / 64 (1.56%)	0 / 42 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Tooth abscess
subjects affected / exposed	0 / 22 (0.00%)	0 / 38 (0.00%)	1 / 64 (1.56%)	1 / 42 (2.38%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Tuberculosis
subjects affected / exposed	0 / 22 (0.00%)	1 / 38 (2.63%)	0 / 64 (0.00%)	0 / 42 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Urinary tract infection
subjects affected / exposed	0 / 22 (0.00%)	1 / 38 (2.63%)	0 / 64 (0.00%)	0 / 42 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Upper respiratory tract infection
subjects affected / exposed	1 / 22 (4.55%)	0 / 38 (0.00%)	1 / 64 (1.56%)	0 / 42 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Metabolism and nutrition disorders
Hypercalcaemia
subjects affected / exposed	0 / 22 (0.00%)	1 / 38 (2.63%)	0 / 64 (0.00%)	0 / 42 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Tumour lysis syndrome
subjects affected / exposed	1 / 22 (4.55%)	3 / 38 (7.89%)	1 / 64 (1.56%)	0 / 42 (0.00%)
occurrences causally related to treatment / all	0 / 1	2 / 3	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0

Frequency threshold for reporting non-serious adverse events: 5%

Non-serious adverse events	1.2 mg/m2/cycle (Run-in)	1.8 mg/m2/cycle (Randomized)	1.2 mg/m2/cycle (Run-in + Randomized)	1.2 mg/m2/cycle (Randomized)
Total subjects affected by non serious adverse events
subjects affected / exposed	18 / 22 (81.82%)	29 / 38 (76.32%)	50 / 64 (78.13%)	32 / 42 (76.19%)
Investigations
Platelet count decreased
subjects affected / exposed	3 / 22 (13.64%)	3 / 38 (7.89%)	3 / 64 (4.69%)	0 / 42 (0.00%)
occurrences all number	3	12	3	0
Neutrophil count decreased
subjects affected / exposed	4 / 22 (18.18%)	4 / 38 (10.53%)	5 / 64 (7.81%)	1 / 42 (2.38%)
occurrences all number	9	17	15	6
Gamma-glutamyltransferase increased
subjects affected / exposed	1 / 22 (4.55%)	6 / 38 (15.79%)	5 / 64 (7.81%)	4 / 42 (9.52%)
occurrences all number	1	6	6	5
Blood lactate dehydrogenase increased
subjects affected / exposed	2 / 22 (9.09%)	4 / 38 (10.53%)	5 / 64 (7.81%)	3 / 42 (7.14%)
occurrences all number	2	4	5	3
Blood alkaline phosphatase increased
subjects affected / exposed	1 / 22 (4.55%)	3 / 38 (7.89%)	3 / 64 (4.69%)	2 / 42 (4.76%)
occurrences all number	2	3	5	3
Aspartate aminotransferase increased
subjects affected / exposed	4 / 22 (18.18%)	8 / 38 (21.05%)	7 / 64 (10.94%)	3 / 42 (7.14%)
occurrences all number	7	10	11	4
Alanine aminotransferase increased
subjects affected / exposed	5 / 22 (22.73%)	3 / 38 (7.89%)	10 / 64 (15.63%)	5 / 42 (11.90%)
occurrences all number	8	6	14	6
SARS-CoV-2 test positive
subjects affected / exposed	0 / 22 (0.00%)	2 / 38 (5.26%)	2 / 64 (3.13%)	2 / 42 (4.76%)
occurrences all number	0	2	2	2
Vascular disorders
Hypertension
subjects affected / exposed	2 / 22 (9.09%)	0 / 38 (0.00%)	2 / 64 (3.13%)	0 / 42 (0.00%)
occurrences all number	2	0	2	0
Nervous system disorders
Headache
subjects affected / exposed	0 / 22 (0.00%)	4 / 38 (10.53%)	4 / 64 (6.25%)	4 / 42 (9.52%)
occurrences all number	0	4	4	4
Blood and lymphatic system disorders
Thrombocytopenia
subjects affected / exposed	5 / 22 (22.73%)	13 / 38 (34.21%)	19 / 64 (29.69%)	14 / 42 (33.33%)
occurrences all number	10	29	40	30
Leukopenia
subjects affected / exposed	2 / 22 (9.09%)	6 / 38 (15.79%)	8 / 64 (12.50%)	6 / 42 (14.29%)
occurrences all number	3	10	9	6
Febrile neutropenia
subjects affected / exposed	1 / 22 (4.55%)	4 / 38 (10.53%)	3 / 64 (4.69%)	2 / 42 (4.76%)
occurrences all number	1	5	4	3
Anaemia
subjects affected / exposed	2 / 22 (9.09%)	6 / 38 (15.79%)	11 / 64 (17.19%)	9 / 42 (21.43%)
occurrences all number	6	9	23	17
Neutropenia
subjects affected / exposed	4 / 22 (18.18%)	10 / 38 (26.32%)	20 / 64 (31.25%)	16 / 42 (38.10%)
occurrences all number	6	26	43	37
General disorders and administration site conditions
Pyrexia
subjects affected / exposed	5 / 22 (22.73%)	1 / 38 (2.63%)	10 / 64 (15.63%)	5 / 42 (11.90%)
occurrences all number	13	1	22	9
Fatigue
subjects affected / exposed	2 / 22 (9.09%)	1 / 38 (2.63%)	4 / 64 (6.25%)	2 / 42 (4.76%)
occurrences all number	2	1	4	2
Asthenia
subjects affected / exposed	0 / 22 (0.00%)	2 / 38 (5.26%)	1 / 64 (1.56%)	1 / 42 (2.38%)
occurrences all number	0	3	1	1
Gastrointestinal disorders
Constipation
subjects affected / exposed	1 / 22 (4.55%)	4 / 38 (10.53%)	3 / 64 (4.69%)	2 / 42 (4.76%)
occurrences all number	2	4	4	2
Abdominal pain upper
subjects affected / exposed	0 / 22 (0.00%)	3 / 38 (7.89%)	1 / 64 (1.56%)	1 / 42 (2.38%)
occurrences all number	0	3	1	1
Abdominal pain
subjects affected / exposed	2 / 22 (9.09%)	1 / 38 (2.63%)	7 / 64 (10.94%)	5 / 42 (11.90%)
occurrences all number	3	1	8	5
Diarrhoea
subjects affected / exposed	0 / 22 (0.00%)	1 / 38 (2.63%)	3 / 64 (4.69%)	3 / 42 (7.14%)
occurrences all number	0	1	4	4
Vomiting
subjects affected / exposed	1 / 22 (4.55%)	3 / 38 (7.89%)	6 / 64 (9.38%)	5 / 42 (11.90%)
occurrences all number	2	5	9	7
Stomatitis
subjects affected / exposed	1 / 22 (4.55%)	2 / 38 (5.26%)	2 / 64 (3.13%)	1 / 42 (2.38%)
occurrences all number	1	4	2	1
Nausea
subjects affected / exposed	0 / 22 (0.00%)	3 / 38 (7.89%)	5 / 64 (7.81%)	5 / 42 (11.90%)
occurrences all number	0	4	5	5
Respiratory, thoracic and mediastinal disorders
Epistaxis
subjects affected / exposed	3 / 22 (13.64%)	4 / 38 (10.53%)	5 / 64 (7.81%)	2 / 42 (4.76%)
occurrences all number	4	4	7	3
Skin and subcutaneous tissue disorders
Rash papular
subjects affected / exposed	1 / 22 (4.55%)	2 / 38 (5.26%)	1 / 64 (1.56%)	0 / 42 (0.00%)
occurrences all number	1	2	1	0
Pruritus
subjects affected / exposed	0 / 22 (0.00%)	0 / 38 (0.00%)	3 / 64 (4.69%)	3 / 42 (7.14%)
occurrences all number	0	0	3	3
Musculoskeletal and connective tissue disorders
Pain in extremity
subjects affected / exposed	0 / 22 (0.00%)	2 / 38 (5.26%)	1 / 64 (1.56%)	1 / 42 (2.38%)
occurrences all number	0	2	1	1
Bone pain
subjects affected / exposed	0 / 22 (0.00%)	3 / 38 (7.89%)	1 / 64 (1.56%)	1 / 42 (2.38%)
occurrences all number	0	4	1	1
Infections and infestations
Pneumonia
subjects affected / exposed	3 / 22 (13.64%)	0 / 38 (0.00%)	4 / 64 (6.25%)	1 / 42 (2.38%)
occurrences all number	3	0	4	1
Influenza
subjects affected / exposed	2 / 22 (9.09%)	0 / 38 (0.00%)	2 / 64 (3.13%)	0 / 42 (0.00%)
occurrences all number	2	0	2	0
Urinary tract infection
subjects affected / exposed	0 / 22 (0.00%)	2 / 38 (5.26%)	2 / 64 (3.13%)	2 / 42 (4.76%)
occurrences all number	0	2	2	2
Metabolism and nutrition disorders
Hypokalaemia
subjects affected / exposed	2 / 22 (9.09%)	1 / 38 (2.63%)	4 / 64 (6.25%)	2 / 42 (4.76%)
occurrences all number	2	1	6	4
Hypomagnesaemia
subjects affected / exposed	1 / 22 (4.55%)	1 / 38 (2.63%)	4 / 64 (6.25%)	3 / 42 (7.14%)
occurrences all number	1	1	5	4

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Were there any global substantial amendments to the protocol? No

Were there any global interruptions to the trial? No

Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.

None reported

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Clinical trials

Clinical Trial Results: A Phase 4, Open-Label, Randomized Study of two Inotuzumab Ozogamicin Dose Levels In Adult Participants With Relapsed Or Refractory B-Cell Acute Lymphoblastic Leukemia Eligible for Hematopoietic Stem Cell Transplantation and who Have Risk Factor(S) for Veno-Occlusive Disease

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Percentage of Subjects With Veno-occlusive Disease (VOD)

Primary: Percentage of Subjects With Veno-occlusive Disease (VOD)

Primary: Rate of Hematologic Remission (Complete Response [CR] / Complete Response with Incomplete Hematologic Recovery[CRi])

Primary: Rate of Hematologic Remission (Complete Response [CR] / Complete Response with Incomplete Hematologic Recovery[CRi])

Secondary: Number of Subjects With Treatment-Emergent Adverse Events (Treatment-related)

Secondary: Number of Subjects With Treatment-Emergent Adverse Events (Treatment-related)

Secondary: Number of Subjects With Treatment-Emergent Adverse Events (All Causalities)

Secondary: Number of Subjects With Treatment-Emergent Adverse Events (All Causalities)

Secondary: Number of Subjects With Treatment-Emergent Serious Adverse Events (Post-HSCT)

Secondary: Number of Subjects With Treatment-Emergent Serious Adverse Events (Post-HSCT)

Secondary: Number of Subjects With Shift Summary of Hematology Laboratory Test Results from Grade Less Than or Equal to (<=) 2 at Baseline to Grade 3 or 4 Post-Baseline

Secondary: Number of Subjects With Shift Summary of Hematology Laboratory Test Results from Grade Less Than or Equal to (<=) 2 at Baseline to Grade 3 or 4 Post-Baseline

Secondary: Number of Subjects With Shift Summary of Chemistry Laboratory Test Results from Grade <=2 at Baseline to Grade 3 or 4 Post-Baseline

Secondary: Number of Subjects With Shift Summary of Chemistry Laboratory Test Results from Grade <=2 at Baseline to Grade 3 or 4 Post-Baseline

Secondary: Number of Subjects Achieving a CR/CRi with Minimal Residual Disease (MRD) Negativity

Secondary: Number of Subjects Achieving a CR/CRi with Minimal Residual Disease (MRD) Negativity

Secondary: Duration of Remission (DoR) in Subjects who Achieved CR/CRi

Secondary: Duration of Remission (DoR) in Subjects who Achieved CR/CRi

Secondary: Number of Subjects who Received HSCT Post Inotuzumab Ozogamicin Treatment

Secondary: Number of Subjects who Received HSCT Post Inotuzumab Ozogamicin Treatment

Secondary: Overall Survival

Secondary: Overall Survival

Secondary: Progression Free Survival (PFS)

Secondary: Progression Free Survival (PFS)

Secondary: Cumulative Incidence Rate of Post-HSCT Relapse at Month 12

Secondary: Cumulative Incidence Rate of Post-HSCT Relapse at Month 12

Secondary: Number of Subjects With Post-HSCT Mortality

Secondary: Number of Subjects With Post-HSCT Mortality

Secondary: Number of Subjects With Post HSCT non-Relapse Mortality

Secondary: Number of Subjects With Post HSCT non-Relapse Mortality

Secondary: Number of Subjects with Post HSCT Relapse-Related Mortality

Secondary: Number of Subjects with Post HSCT Relapse-Related Mortality

Secondary: Mean Predose Concentrations (Ctrough) of Inotuzumab Ozogamicin

Secondary: Mean Predose Concentrations (Ctrough) of Inotuzumab Ozogamicin

Secondary: Number of Subjects With Positive Anti-Drug Antibody (ADA)

Secondary: Number of Subjects With Positive Anti-Drug Antibody (ADA)

Secondary: Number of Subjects With Positive Neutralizing Antibody (NAb)

Secondary: Number of Subjects With Positive Neutralizing Antibody (NAb)

Adverse events

Adverse events

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Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

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Clinical Trial Results:
A Phase 4, Open-Label, Randomized Study of two Inotuzumab Ozogamicin Dose Levels In Adult Participants With Relapsed Or Refractory B-Cell Acute Lymphoblastic Leukemia Eligible for Hematopoietic Stem Cell Transplantation and who Have Risk Factor(S) for Veno-Occlusive Disease