A Study Of Inotuzumab Ozogamicin Versus Investigator's Choice Of Chemotherapy In Patients With Relapsed Or Refractory Acute Lymphoblastic Leukemia

• ClinicalTrials.gov Identifier: NCT01564784
• Recruitment Status: Completed
• First Posted: March 28, 2012
• Results First Posted: January 17, 2018
• Last Update Posted: January 9, 2019
• Sponsor: Pfizer
• Collaborator: UCB Pharma
• Information provided by (Responsible Party): Pfizer

• Study Type: Interventional
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Acute Lymphoblastic Leukemia
• Interventions: Drug: inotuzumab ozogamicin; Drug: FLAG (fludarabine, cytarabine and G-CSF); Drug: HIDAC (high dose cytarabine); Drug: cytarabine and mitoxantrone
• Enrollment: 326

Participant Flow

Recruitment Details
Pre-assignment Details	164 participants were randomized to Inotuzumab Ozogamicin and 162 to Defined Investigator's Choice of Chemotherapy. Although only 143 participants were treated in the Defined Investigator's Choice of Chemotherapy arm, all 162 randomized participants were included in the intention-to-treat (ITT) population.

Arm/Group Title	Inotuzumab Ozogamicin	Defined Investigator's Choice of Chemotherapy
Arm/Group Description	Participants were treated with inotuzumab ozogamicin at a starting dose of 1.8 mg/m^2 (according to body surface area) per cycle with a divided-dose regimen using 3 weekly administrations. Participants received 0.8 mg/m^2/cycle on Week 1 (Day 1), followed by 0.5 mg/m^2 on Week 2 (Day 8) and Week 3 (Day 15) of a 21-day cycle, and administered as an intravenous infusion over 60 minutes. For participants who achieved a CR or CRi, or to allow recovery from toxicity, the length of Cycle 1 could be extended up to 28 days (ie, 1 week treatment-free interval starting on Day 21). For participants who achieved CR or CRi, the inotuzumab ozogamicin dose administered on Week 1 was reduced to 0.5 mg/m^2 (for a total cycle dose of 1.5 mg/m^2/cycle) for Cycles 2 through 6 (maximum number of cycles permitted). For Cycles 2 through 6, the cycle length was 28 days for all participants (regardless of remission status).	Participants received fludarabine, cytarabine, granulocyte-colony stimulating factor (FLAG), mitoxantrone + cytarabine (MXN/Ara-C), or high-dose cytarabine (HIDAC), according to the Investigator's choice.
Period Title: Overall Study
Started	164 [1]	143 [2]
Completed	30	10
Not Completed	134	133
Reason Not Completed
Other	1	0
Subject refused further follow-up	1	6
Lost to Follow-up	1	1
Death	131	126
[1] Treated (164 randomized); [2] Treated (162 randomized)

Baseline Characteristics

Arm/Group Title		Inotuzumab Ozogamicin	Defined Investigator's Choice of Chemotherapy	Total
Arm/Group Description		Participants were treated with inotuzumab ozogamicin at a starting dose of 1.8 mg/m^2 (according to body surface area) per cycle with a divided-dose regimen using 3 weekly administrations. Participants received 0.8 mg/m^2/cycle on Week 1 (Day 1), followed by 0.5 mg/m^2 on Week 2 (Day 8) and Week 3 (Day 15) of a 21-day cycle, and administered as an intravenous infusion over 60 minutes. For participants who achieved a CR or CRi, or to allow recovery from toxicity, the length of Cycle 1 could be extended up to 28 days (ie, 1 week treatment-free interval starting on Day 21). For participants who achieved CR or CRi, the inotuzumab ozogamicin dose administered on Week 1 was reduced to 0.5 mg/m^2 (for a total cycle dose of 1.5 mg/m^2/cycle) for Cycles 2 through 6 (maximum number of cycles permitted). For Cycles 2 through 6, the cycle length was 28 days for all participants (regardless of remission status).	Participants received fludarabine, cytarabine, granulocyte-colony stimulating factor (FLAG), mitoxantrone + cytarabine (MXN/Ara-C), or high-dose cytarabine (HIDAC), according to the Investigator's choice.	Total of all reporting groups
Overall Number of Baseline Participants		164	143	307
Baseline Analysis Population Description		[Not Specified]
Age, Continuous; Mean (Standard Deviation); Unit of measure: Years
	Number Analyzed	164 participants	143 participants	307 participants
		45.9 (17.07)	45.6 (16.32)	45.7 (16.70)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	164 participants	143 participants	307 participants
	Female	73 44.5%	51 35.7%	124 40.4%
	Male	91 55.5%	92 64.3%	183 59.6%

Outcome Measures

1. Primary Outcome

Title	Percentage of Participants With Hematologic Remission (Complete Remission [CR]/Complete Remission With Incomplete Hematologic Recovery [CRi]) as Assessed by the Endpoint Adjudication Committee (EAC)
Description	CR was the disappearance of leukemia indicated by less than (<) 5 percent (%) marrow blasts & absence of peripheral blood leukemic blasts, with recovery of hematopoiesis defined by absolute neutrophil count (ANC) greater than or equal to (≥)1000 per microliter (/μL) & platelets ≥100,000/μL. C1 extramedullary disease status (i.e. complete disappearance of measurable & non-measurable extramedullary disease with the following exceptions: for participants with at least 1 measurable lesion, all nodal masses greater than (>) 1.5 centimeters (cm) in greatest transverse diameter (GTD) at baseline must have regressed to less than or equal to (≤) 1.5 cm in GTD; all nodal masses ≥1 cm & ≤1.5 cm in GTD at baseline must have regressed to <1 cm GTD or reduced by 75% in sum of products of greatest diameters, no new lesions, spleen & other previously enlarged organs must have regressed in size & must not be palpable) was required. CRi was defined as CR except ANC <1000/μL &/or platelets <100,000/μL.
Time Frame	Screening, Day 16 to 28 of Cycles 1, 2 and 3, then every 1 to 2 cycles (or as clinically indicated) up to approximately 4 weeks (end of treatment [EoT]) from the last dose

Outcome Measure Data

Analysis Population Description

ITT218 population - included the ITT population (all participants randomized) for the initial 218 participants.

Arm/Group Title	Inotuzumab Ozogamicin	Defined Investigator's Choice of Chemotherapy
Arm/Group Description:	Participants were treated with inotuzumab ozogamicin at a starting dose of 1.8 mg/m^2 (according to body surface area) per cycle with a divided-dose regimen using 3 weekly administrations. Participants received 0.8 mg/m^2/cycle on Week 1 (Day 1), followed by 0.5 mg/m^2 on Week 2 (Day 8) and Week 3 (Day 15) of a 21-day cycle, and administered as an intravenous infusion over 60 minutes. For participants who achieved a CR or CRi, or to allow recovery from toxicity, the length of Cycle 1 could be extended up to 28 days (ie, 1 week treatment-free interval starting on Day 21). For participants who achieved CR or CRi, the inotuzumab ozogamicin dose administered on Week 1 was reduced to 0.5 mg/m^2 (for a total cycle dose of 1.5 mg/m^2/cycle) for Cycles 2 through 6 (maximum number of cycles permitted). For Cycles 2 through 6, the cycle length was 28 days for all participants (regardless of remission status).	Participants received fludarabine, cytarabine, granulocyte-colony stimulating factor (FLAG), mitoxantrone + cytarabine (MXN/Ara-C), or high-dose cytarabine (HIDAC), according to the Investigator's choice.
Overall Number of Participants Analyzed	109	109
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: Percentage of Participants
	80.7; (72.1 to 87.7)	29.4; (21.0 to 38.8)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Inotuzumab Ozogamicin, Defined Investigator's Choice of Chemotherapy
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.0001
	Comments	[Not Specified]
	Method	1-sided p-value based on Chi-square test
	Comments	If any cell count was <5, p-value was based on Fisher's exact test
Method of Estimation	Estimation Parameter	Rate difference
	Estimated Value	51.4
	Confidence Interval	(2-Sided) 97.5%; 38.4 to 64.3
	Estimation Comments	[Not Specified]

2. Primary Outcome

Title	Overall Survival (OS)
Description	OS was defined as the time from randomization to date of death due to any cause. Participants last known to be alive were censored at date of last contact.
Time Frame	Up to 5 years after randomization or 2 years from randomization of the last participant, whichever occurs first.

Outcome Measure Data

Analysis Population Description

ITT population - included all participants randomized. Although only 143 participants were treated in the Defined Investigator's Choice of Chemotherapy arm, all 162 randomized participants were included in the ITT population.

Arm/Group Title	Inotuzumab Ozogamicin	Defined Investigator's Choice of Chemotherapy
Arm/Group Description:	Participants were treated with inotuzumab ozogamicin at a starting dose of 1.8 mg/m^2 (according to body surface area) per cycle with a divided-dose regimen using 3 weekly administrations. Participants received 0.8 mg/m^2/cycle on Week 1 (Day 1), followed by 0.5 mg/m^2 on Week 2 (Day 8) and Week 3 (Day 15) of a 21-day cycle, and administered as an intravenous infusion over 60 minutes. For participants who achieved a CR or CRi, or to allow recovery from toxicity, the length of Cycle 1 could be extended up to 28 days (ie, 1 week treatment-free interval starting on Day 21). For participants who achieved CR or CRi, the inotuzumab ozogamicin dose administered on Week 1 was reduced to 0.5 mg/m^2 (for a total cycle dose of 1.5 mg/m^2/cycle) for Cycles 2 through 6 (maximum number of cycles permitted). For Cycles 2 through 6, the cycle length was 28 days for all participants (regardless of remission status).	Participants received fludarabine, cytarabine, granulocyte-colony stimulating factor (FLAG), mitoxantrone + cytarabine (MXN/Ara-C), or high-dose cytarabine (HIDAC), according to the Investigator's choice.
Overall Number of Participants Analyzed	164	162
Median (95% Confidence Interval); Unit of Measure: Months
	7.7; (6.0 to 9.2)	6.2; (4.7 to 8.3)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Inotuzumab Ozogamicin, Defined Investigator's Choice of Chemotherapy
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.0105
	Comments	[Not Specified]
	Method	1-sided stratified log-rank p-value
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.751
	Confidence Interval	(2-Sided) 97.5%; 0.568 to 0.993
	Estimation Comments	Stratified HR, i.e., based on analysis stratified by randomization stratification factors.

3. Secondary Outcome

Title	Duration of Remission (DoR) for Participants Who Achieved CR/CRi (Per Investigator Assessment)
Description	DoR was defined as time from date of first response in responders (CR/CRi per Investigator assessment) to date of PFS event (i.e. death, progressive disease [objective progression, relapse from CR/CRi or treatment discontinuation due to global deterioration of health status] or starting new induction therapy or post-therapy stem cell transplant [SCT] without achieving CR/CRi). Responders without PFS events were censored at the last valid disease assessment including follow-up.
Time Frame	Up to 2 years from randomization

Outcome Measure Data

Analysis Population Description

Participants in the ITT218 population who achieved CR/CRi

Arm/Group Title	Inotuzumab Ozogamicin	Defined Investigator's Choice of Chemotherapy
Arm/Group Description:	Participants were treated with inotuzumab ozogamicin at a starting dose of 1.8 mg/m^2 (according to body surface area) per cycle with a divided-dose regimen using 3 weekly administrations. Participants received 0.8 mg/m^2/cycle on Week 1 (Day 1), followed by 0.5 mg/m^2 on Week 2 (Day 8) and Week 3 (Day 15) of a 21-day cycle, and administered as an intravenous infusion over 60 minutes. For participants who achieved a CR or CRi, or to allow recovery from toxicity, the length of Cycle 1 could be extended up to 28 days (ie, 1 week treatment-free interval starting on Day 21). For participants who achieved CR or CRi, the inotuzumab ozogamicin dose administered on Week 1 was reduced to 0.5 mg/m^2 (for a total cycle dose of 1.5 mg/m^2/cycle) for Cycles 2 through 6 (maximum number of cycles permitted). For Cycles 2 through 6, the cycle length was 28 days for all participants (regardless of remission status).	Participants received fludarabine, cytarabine, granulocyte-colony stimulating factor (FLAG), mitoxantrone + cytarabine (MXN/Ara-C), or high-dose cytarabine (HIDAC), according to the Investigator's choice.
Overall Number of Participants Analyzed	85	32
Median (95% Confidence Interval); Unit of Measure: Months
	5.4; (4.3 to 8.0)	3.5; (2.2 to 6.6)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Inotuzumab Ozogamicin, Defined Investigator's Choice of Chemotherapy
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.0021
	Comments	[Not Specified]
	Method	1-sided stratified log-rank p-value
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.490
	Confidence Interval	(2-Sided) 95%; 0.297 to 0.809
	Estimation Comments	Stratified HR, i.e., based on analysis stratified by randomization stratification factors.

4. Secondary Outcome

Title	Progression-Free Survival (PFS)
Description	PFS was defined as time from date of randomization to earliest date of the following events: death, progressive disease (objective progression, relapse from CR/CRi or treatment discontinuation due to global deterioration of health status) and starting new induction therapy or post-therapy SCT without achieving CR/CRi. Participants without a PFS event at time of analysis were censored at the last valid disease assessment. In addition, participants with documentation of an event after an unacceptably long interval (>28 weeks if there was post-baseline disease assessment, or >12 weeks if there was no post-baseline assessment) since the previous disease assessment were censored at the time of the previous assessment (date of randomization if no post-baseline assessment). Post-study treatment follow-up disease assessments was included. Kaplan-Meier method used and 2-sided 95% confidence interval (CI) calculated based on the Brookmeyer and Crowley method.
Time Frame	Up to 2 years from randomization

Outcome Measure Data

Analysis Population Description

ITT population. Although only 143 participants were treated in the Defined Investigator's Choice of Chemotherapy arm, all 162 randomized participants were included in the ITT population.

Arm/Group Title	Inotuzumab Ozogamicin	Defined Investigator's Choice of Chemotherapy
Arm/Group Description:	Participants were treated with inotuzumab ozogamicin at a starting dose of 1.8 mg/m^2 (according to body surface area) per cycle with a divided-dose regimen using 3 weekly administrations. Participants received 0.8 mg/m^2/cycle on Week 1 (Day 1), followed by 0.5 mg/m^2 on Week 2 (Day 8) and Week 3 (Day 15) of a 21-day cycle, and administered as an intravenous infusion over 60 minutes. For participants who achieved a CR or CRi, or to allow recovery from toxicity, the length of Cycle 1 could be extended up to 28 days (ie, 1 week treatment-free interval starting on Day 21). For participants who achieved CR or CRi, the inotuzumab ozogamicin dose administered on Week 1 was reduced to 0.5 mg/m^2 (for a total cycle dose of 1.5 mg/m^2/cycle) for Cycles 2 through 6 (maximum number of cycles permitted). For Cycles 2 through 6, the cycle length was 28 days for all participants (regardless of remission status).	Participants received fludarabine, cytarabine, granulocyte-colony stimulating factor (FLAG), mitoxantrone + cytarabine (MXN/Ara-C), or high-dose cytarabine (HIDAC), according to the Investigator's choice.
Overall Number of Participants Analyzed	164	162
Median (95% Confidence Interval); Unit of Measure: Months
	5.0; (3.9 to 5.8)	1.7; (1.4 to 2.1)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Inotuzumab Ozogamicin, Defined Investigator's Choice of Chemotherapy
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.0001
	Comments	[Not Specified]
	Method	1-sided stratified log-rank p-value
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.450
	Confidence Interval	(2-Sided) 97.5%; 0.336 to 0.602
	Estimation Comments	Stratified HR, i.e., based on analysis stratified by randomization stratification factors.

5. Secondary Outcome

Title	Percentage of Participants Who Had a Hematopoietic Stem-Cell Transplant (HSCT)
Description	HSCT rate was defined as the percentage of participants who underwent SCT following treatment with inotuzumab ozogamicin or Investigator's choice of chemotherapy.
Time Frame	Up to 19 weeks from last dose

Outcome Measure Data

Analysis Population Description

ITT population. Although only 143 participants were treated in the Defined Investigator's Choice of Chemotherapy arm, all 162 randomized participants were included in the ITT population.

Arm/Group Title	Inotuzumab Ozogamicin	Defined Investigator's Choice of Chemotherapy
Arm/Group Description:	Participants were treated with inotuzumab ozogamicin at a starting dose of 1.8 mg/m^2 (according to body surface area) per cycle with a divided-dose regimen using 3 weekly administrations. Participants received 0.8 mg/m^2/cycle on Week 1 (Day 1), followed by 0.5 mg/m^2 on Week 2 (Day 8) and Week 3 (Day 15) of a 21-day cycle, and administered as an intravenous infusion over 60 minutes. For participants who achieved a CR or CRi, or to allow recovery from toxicity, the length of Cycle 1 could be extended up to 28 days (ie, 1 week treatment-free interval starting on Day 21). For participants who achieved CR or CRi, the inotuzumab ozogamicin dose administered on Week 1 was reduced to 0.5 mg/m^2 (for a total cycle dose of 1.5 mg/m^2/cycle) for Cycles 2 through 6 (maximum number of cycles permitted). For Cycles 2 through 6, the cycle length was 28 days for all participants (regardless of remission status).	Participants received fludarabine, cytarabine, granulocyte-colony stimulating factor (FLAG), mitoxantrone + cytarabine (MXN/Ara-C), or high-dose cytarabine (HIDAC), according to the Investigator's choice.
Overall Number of Participants Analyzed	164	162
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: Percentage of Participants
	42.7; (35.0 to 50.6)	11.1; (6.7 to 17.0)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Inotuzumab Ozogamicin, Defined Investigator's Choice of Chemotherapy
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.0001
	Comments	[Not Specified]
	Method	1-sided p-value based on Chi-square test
	Comments	If any cell count was <5, p-value was based on Fisher's exact test
Method of Estimation	Estimation Parameter	Rate difference
	Estimated Value	31.6
	Confidence Interval	(2-Sided) 95%; 22.6 to 40.6
	Estimation Comments	[Not Specified]

6. Secondary Outcome

Title	Percentage of Participants Achieving MRD Negativity (Based on Central Laboratory Analysis) in Participants Achieving a CR/CRi (Per EAC Assessment)
Description	MRD analysis was performed at least once in participants with prior assessment of CR or CRi. Bone marrow aspirates, collected at screening and during the study, were sent to the central laboratory and analyzed using multiparametric flow cytometry. The antibody combinations were designed to maximize discrimination between normal and abnormal cells of B-cell lineage and similar maturational stage and included antibodies detecting cluster of differentiation (CD) 9, CD10, CD13, CD19, CD20, CD33, CD34, CD38, CD45, CD58, CD66c, and CD123. A peripheral blood sample was provided if a participant had an inadequate bone marrow aspirate at screening. MRD negativity was considered to have been achieved if the lowest value of MRD from the first date of CR/CRi to EoT was <1 × 10^-4 blasts/nucleated cells.
Time Frame	Up to approximately 4 weeks (EoT) from last dose of study drug

Outcome Measure Data

Analysis Population Description

Participants in the ITT218 population achieving CR/CRi (per EAC Assessment)

Arm/Group Title	Inotuzumab Ozogamicin	Defined Investigator's Choice of Chemotherapy
Arm/Group Description:	Participants were treated with inotuzumab ozogamicin at a starting dose of 1.8 mg/m^2 (according to body surface area) per cycle with a divided-dose regimen using 3 weekly administrations. Participants received 0.8 mg/m^2/cycle on Week 1 (Day 1), followed by 0.5 mg/m^2 on Week 2 (Day 8) and Week 3 (Day 15) of a 21-day cycle, and administered as an intravenous infusion over 60 minutes. For participants who achieved a CR or CRi, or to allow recovery from toxicity, the length of Cycle 1 could be extended up to 28 days (ie, 1 week treatment-free interval starting on Day 21). For participants who achieved CR or CRi, the inotuzumab ozogamicin dose administered on Week 1 was reduced to 0.5 mg/m^2 (for a total cycle dose of 1.5 mg/m^2/cycle) for Cycles 2 through 6 (maximum number of cycles permitted). For Cycles 2 through 6, the cycle length was 28 days for all participants (regardless of remission status).	Participants received fludarabine, cytarabine, granulocyte-colony stimulating factor (FLAG), mitoxantrone + cytarabine (MXN/Ara-C), or high-dose cytarabine (HIDAC), according to the Investigator's choice.
Overall Number of Participants Analyzed	88	32
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: Percentage of Participants
	78.4; (68.4 to 86.5)	28.1; (13.7 to 46.7)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Inotuzumab Ozogamicin, Defined Investigator's Choice of Chemotherapy
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.0001
	Comments	[Not Specified]
	Method	1-sided p-value based on Chi-Square test
	Comments	If any cell count is <5, p-value was based on Fisher's exact test

7. Secondary Outcome

Title	Cytogenetic Status (Based on Local Laboratory Analysis) of Participants With CR/CRi (Per EAC Assessment)
Description	Karyotyping was required locally, at screening and at least once during the study in participants who had abnormal cytogenetics at baseline and who achieved CR/CRi. Data presented below are for participants who achieved CR/CRi per EAC and had abnormal karyotype at screening.
Time Frame	Up to approximately 4 weeks (EoT) from last dose of study drug

Outcome Measure Data

Analysis Population Description

Participants in the ITT218 population who had abnormal cytogenetics at baseline and who achieved CR/CRi

Arm/Group Title	Inotuzumab Ozogamicin	Defined Investigator's Choice of Chemotherapy
Arm/Group Description:	Participants were treated with inotuzumab ozogamicin at a starting dose of 1.8 mg/m^2 (according to body surface area) per cycle with a divided-dose regimen using 3 weekly administrations. Participants received 0.8 mg/m^2/cycle on Week 1 (Day 1), followed by 0.5 mg/m^2 on Week 2 (Day 8) and Week 3 (Day 15) of a 21-day cycle, and administered as an intravenous infusion over 60 minutes. For participants who achieved a CR or CRi, or to allow recovery from toxicity, the length of Cycle 1 could be extended up to 28 days (ie, 1 week treatment-free interval starting on Day 21). For participants who achieved CR or CRi, the inotuzumab ozogamicin dose administered on Week 1 was reduced to 0.5 mg/m^2 (for a total cycle dose of 1.5 mg/m^2/cycle) for Cycles 2 through 6 (maximum number of cycles permitted). For Cycles 2 through 6, the cycle length was 28 days for all participants (regardless of remission status).	Participants received fludarabine, cytarabine, granulocyte-colony stimulating factor (FLAG), mitoxantrone + cytarabine (MXN/Ara-C), or high-dose cytarabine (HIDAC), according to the Investigator's choice.
Overall Number of Participants Analyzed	54	22
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: Percentage of Participants
	3.7; (0.5 to 12.7)	18.2; (5.2 to 40.3)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Inotuzumab Ozogamicin, Defined Investigator's Choice of Chemotherapy
	Comments	Abnormal at Screening
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.3168
	Comments	[Not Specified]
	Method	1-sided p-value based on Chi-Square test
	Comments	If any cell count is <5, p-value was based on Fisher's exact test

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Inotuzumab Ozogamicin, Defined Investigator's Choice of Chemotherapy
	Comments	Abnormal after remission
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.2160
	Comments	[Not Specified]
	Method	1-sided p-value based on Chi-Square test
	Comments	If any cell count is <5, p-value was based on Fisher's exact test

8. Secondary Outcome

Title	Maximum Observed Inotuzumab Ozogamicin Serum Concentration (Cmax) and Pre-Dose Inotuzumab Ozogamicin Serum Concentration (Ctrough) Following Single and Multiple Dosing
Description	Blood samples were collected and analyzed for inotuzumab ozogamicin serum concentrations using a validated high performance liquid chromatography with tandem mass spectrometry (HPLC/MS/MS) method with a lower limit of quantification of 1.0 nanograms per milliliter (ng/mL). Cmax was the maximum observed concentration occurring between 0-8 hours post-dose. Ctrough was the concentration prior to subsequent dose (pre-dose) occurring after 8 hours. n = number of observations (non-missing concentrations).
Time Frame	Days 1, 4, 8, and 15 of Cycle 1, Days 1 and 8 of Cycle 2 and Day 1 of Cycle 4

Outcome Measure Data

Analysis Population Description

Pharmacokinetic (PK) evaluable population - included all participants with available PK data.

Arm/Group Title	Inotuzumab Ozogamicin
Arm/Group Description:	Participants were treated with inotuzumab ozogamicin at a starting dose of 1.8 mg/m^2 (according to body surface area) per cycle with a divided-dose regimen using 3 weekly administrations. Participants received 0.8 mg/m^2/cycle on Week 1 (Day 1), followed by 0.5 mg/m^2 on Week 2 (Day 8) and Week 3 (Day 15) of a 21-day cycle, and administered as an intravenous infusion over 60 minutes. For participants who achieved a CR or CRi, or to allow recovery from toxicity, the length of Cycle 1 could be extended up to 28 days (ie, 1 week treatment-free interval starting on Day 21). For participants who achieved CR or CRi, the inotuzumab ozogamicin dose administered on Week 1 was reduced to 0.5 mg/m^2 (for a total cycle dose of 1.5 mg/m^2/cycle) for Cycles 2 through 6 (maximum number of cycles permitted). For Cycles 2 through 6, the cycle length was 28 days for all participants (regardless of remission status).
Overall Number of Participants Analyzed	163
Mean (Standard Deviation); Unit of Measure: ng/mL
Cmax (Cycle 1 Day 1, 1 hour post-dose) (n=128)	211 (232)
Ctrough (Cycle 4 Day 1, pre-dose) (n=46)	57.9 (29.8)
Cmax (Cycle 4 Day 1, 1 hour post-dose) (n=37)	308 (362)

9. Secondary Outcome

Title	Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire, Core 30 (EORTC QLQ-C30) Score
Description	This questionnaire comprised 30 questions within which are 9 multi-item scales & 6 single-item measures. There are 5 functional scales; physical, role, cognitive, emotional & social, 3 symptom scales; fatigue, pain, & nausea & vomiting, & a global health status/quality of life (QoL) scale. There are 5 single item measures assessing additional symptoms commonly reported by cancer patients (loss of appetite, insomnia, constipation, diarrhea, & dyspnea) & a single item concerning perceived financial impact of the disease. Most questions used a 4 point scale (1='not at all' to 4='very much'); 2 questions used a 7-point scale (1='very poor' to 7='excellent'). Scores were averaged & transformed to a scale ranging from 0 to 100; a higher score indicates a better level of functioning or greater degree of symptoms.
Time Frame	Day 1 of each cycle prior to dosing and EoT

Outcome Measure Data

Analysis Population Description

ITT population. Although only 143 participants were treated in the Defined Investigator's Choice of Chemotherapy arm, all 162 randomized participants were included in the ITT population

Arm/Group Title	Inotuzumab Ozogamicin	Defined Investigator's Choice of Chemotherapy
Arm/Group Description:	Participants were treated with inotuzumab ozogamicin at a starting dose of 1.8 mg/m^2 (according to body surface area) per cycle with a divided-dose regimen using 3 weekly administrations. Participants received 0.8 mg/m^2/cycle on Week 1 (Day 1), followed by 0.5 mg/m^2 on Week 2 (Day 8) and Week 3 (Day 15) of a 21-day cycle, and administered as an intravenous infusion over 60 minutes. For participants who achieved a CR or CRi, or to allow recovery from toxicity, the length of Cycle 1 could be extended up to 28 days (ie, 1 week treatment-free interval starting on Day 21). For participants who achieved CR or CRi, the inotuzumab ozogamicin dose administered on Week 1 was reduced to 0.5 mg/m^2 (for a total cycle dose of 1.5 mg/m^2/cycle) for Cycles 2 through 6 (maximum number of cycles permitted). For Cycles 2 through 6, the cycle length was 28 days for all participants (regardless of remission status).	Participants received fludarabine, cytarabine, granulocyte-colony stimulating factor (FLAG), mitoxantrone + cytarabine (MXN/Ara-C), or high-dose cytarabine (HIDAC), according to the Investigator's choice.
Overall Number of Participants Analyzed	164	162
Mean (Standard Error); Unit of Measure: Score on a scale
Physical Functioning C2D1	0.48 (1.53)	0.32 (3.55)
Physical Functioning C3D1	3.15 (1.97)	-13.33 (7.70)
Physical Functioning C4D1	5.33 (2.84)	0.00 [1] (NA)
Physical Functioning C5D1	11.52 (3.51)	NA [2] (NA)
Physical Functioning C6D1	7.22 (5.94)	NA [2] (NA)
Physical Functioning EoT	-3.38 (2.03)	-8.17 (2.67)
Role Functioning C2D1	5.45 (2.79)	-1.59 (8.21)
Role Functioning C3D1	11.81 (3.19)	-11.11 (5.56)
Role Functioning C4D1	16.67 (5.47)	0.00 [1] (NA)
Role Functioning C5D1	12.88 (6.10)	NA [2] (NA)
Role Functioning C6D1	16.67 (11.42)	NA [2] (NA)
Role Functioning EoT	1.32 (3.59)	-12.37 (4.09)
Emotional Functioning C2D1	5.21 (1.76)	4.76 (6.77)
Emotional Functioning C3D1	7.41 (1.85)	-19.44 (10.02)
Emotional Functioning C4D1	5.69 (1.63)	0.00 [1] (NA)
Emotional Functioning C5D1	6.82 (2.83)	NA [2] (NA)
Emotional Functioning C6D1	2.78 (4.27)	NA [2] (NA)
Emotional Functioning EoT	-0.91 (1.80)	4.35 (2.96)
Cognitive Functioning C2D1	4.05 (1.47)	0.00 (3.98)
Cognitive Functioning C3D1	5.79 (2.11)	-5.56 (14.70)
Cognitive Functioning C4D1	4.58 (2.86)	16.67 [1] (NA)
Cognitive Functioning C5D1	0.76 (4.17)	NA [2] (NA)
Cognitive Functioning C6D1	-8.33 (2.51)	NA [2] (NA)
Cognitive Functioning EoT	0.83 (1.82)	0.54 (2.89)
Social Functioning C2D1	4.20 (2.46)	-2.38 (7.21)
Social Functioning C3D1	5.56 (3.25)	-27.78 (20.03)
Social Functioning C4D1	10.42 (4.95)	0.00 [1] (NA)
Social Functioning C5D1	12.88 (6.00)	NA [2] (NA)
Social Functioning C6D1	16.67 (5.03)	NA [2] (NA)
Social Functioning EoT	1.82 (2.84)	-2.15 (4.78)
Global Health Status C2D1	3.98 (2.03)	0.40 (4.62)
Global Health Status C3D1	9.38 (3.15)	-16.67 (12.73)
Global Health Status C4D1	11.25 (3.69)	8.33 [1] (NA)
Global Health Status C5D1	8.71 (6.68)	NA [2] (NA)
Global Health Status C6D1	0.69 (6.76)	NA [2] (NA)
Global Health Status EoT	0.00 (2.83)	-0.40 (3.28)
Dyspnoea C2D1	-5.41 (2.72)	-7.94 (6.47)
Dyspnoea C3D1	-7.41 (3.24)	11.11 (11.11)
Dyspnoea C4D1	-12.50 (4.25)	0.00 [1] (NA)
Dyspnoea C5D1	-3.03 (6.55)	NA [2] (NA)
Dyspnoea C6D1	-2.78 (6.43)	NA [2] (NA)
Dyspnoea EoT	-2.31 (3.09)	0.54 (3.95)
Insomnia C2D1	-2.40 (3.01)	1.59 (5.85)
Insomnia C3D1	-9.26 (3.38)	0.00 (19.25)
Insomnia C4D1	-7.50 (3.27)	0.00 [1] (NA)
Insomnia C5D1	-4.55 (4.55)	NA [2] (NA)
Insomnia C6D1	-11.11 (9.48)	NA [2] (NA)
Insomnia EoT	-2.31 (3.09)	0.00 (3.91)
Appetite Loss C2D1	-4.20 (2.83)	3.17 (7.24)
Appetite Loss C3D1	-8.33 (4.31)	0.00 (0.00)
Appetite Loss C4D1	-11.67 (5.54)	0.00 [1] (NA)
Appetite Loss C5D1	-6.06 (7.80)	NA [2] (NA)
Appetite Loss C6D1	2.78 (9.59)	NA [2] (NA)
Appetite Loss EoT	-1.32 (3.54)	11.83 (4.41)
Constipation C2D1	-1.21 (2.47)	0.00 (5.14)
Constipation C3D1	0.47 (3.44)	0.00 (0.00)
Constipation C4D1	-2.50 (3.66)	0.00 [1] (NA)
Constipation C5D1	0.00 (5.37)	NA [2] (NA)
Constipation C6D1	5.56 (5.56)	NA [2] (NA)
Constipation EoT	2.64 (2.60)	-0.54 (2.71)
Diarrhoea C2D1	-3.30 (2.17)	-1.59 (4.87)
Diarrhoea C3D1	-5.09 (2.61)	-11.11 (11.11)
Diarrhoea C4D1	-0.83 (3.27)	0.00 [1] (NA)
Diarrhoea C5D1	-9.52 (4.68)	NA [2] (NA)
Diarrhoea C6D1	-2.78 (4.95)	NA [2] (NA)
Diarrhoea EoT	2.31 (1.89)	3.76 (3.35)
Financial Difficulties C2D1	-1.80 (1.99)	0.00 (8.72)
Financial Difficulties C3D1	0.47 (3.24)	0.00 (0.00)
Financial Difficulties C4D1	-1.67 (3.37)	0.00 [1] (NA)
Financial Difficulties C5D1	-3.03 (3.74)	NA [2] (NA)
Financial Difficulties C6D1	-5.56 (3.75)	NA [2] (NA)
Financial Difficulties EoT	0.33 (3.09)	2.19 (2.80)
Fatigue C2D1	-4.10 (2.40)	5.82 (6.88)
Fatigue C3D1	-8.33 (3.02)	22.22 (6.42)
Fatigue C4D1	-9.17 (4.64)	-11.11 [1] (NA)
Fatigue C5D1	-7.32 (5.61)	NA [2] (NA)
Fatigue C6D1	0.00 (6.42)	NA [2] (NA)
Fatigue Eot	-0.33 (2.66)	5.73 (3.27)
Nausea and Vomiting C2D1	0.15 (2.16)	-0.79 (2.69)
Nausea and Vomiting C3D1	-4.63 (2.80)	0.00 (0.00)
Nausea and Vomiting C4D1	-3.33 (3.17)	-16.67 [1] (NA)
Nausea and Vomiting C5D1	2.27 (2.96)	NA [2] (NA)
Nausea and Vomiting C6D1	0.00 (2.90)	NA [2] (NA)
Nausea and Vomiting EoT	-0.17 (2.33)	3.49 (2.43)
Pain C2D1	-8.86 (2.71)	-7.14 (7.68)
Pain C3D1	-8.56 (3.73)	-5.56 (14.70)
Pain C4D1	-4.17 (3.81)	-33.33 [1] (NA)
Pain C5D1	0.76 (7.48)	NA [2] (NA)
Pain C6D1	-2.78 (9.59)	NA [2] (NA)
Pain EoT	-1.98 (2.88)	-7.26 (3.75)

[1]

n=1

[2]

n=0

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Inotuzumab Ozogamicin, Defined Investigator's Choice of Chemotherapy
	Comments	Physical Functioning
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.0139
	Comments	[Not Specified]
	Method	Mixed Models Analysis
	Comments	Treatment, time, treatment-by-time interaction, and baseline included as covariate.
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	6.9
	Confidence Interval	(2-Sided) 95%; 1.4 to 12.3
	Estimation Comments	[Not Specified]

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Inotuzumab Ozogamicin, Defined Investigator's Choice of Chemotherapy
	Comments	Role Functioning
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.0065
	Comments	[Not Specified]
	Method	Mixed Models Analysis
	Comments	Treatment, time, treatment-by-time interaction, and baseline included as covariate.
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	11.4
	Confidence Interval	(2-Sided) 95%; 3.2 to 19.5
	Estimation Comments	[Not Specified]

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Inotuzumab Ozogamicin, Defined Investigator's Choice of Chemotherapy
	Comments	Emotional Functioning
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.3307
	Comments	[Not Specified]
	Method	Mixed Models Analysis
	Comments	Treatment, time, treatment-by-time interaction, and baseline included as covariate.
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-2.3
	Confidence Interval	(2-Sided) 95%; -6.9 to 2.3
	Estimation Comments	[Not Specified]

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Inotuzumab Ozogamicin, Defined Investigator's Choice of Chemotherapy
	Comments	Cognitive Functioning
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.1904
	Comments	[Not Specified]
	Method	Mixed Models Analysis
	Comments	Treatment, time, treatment-by-time interaction, and baseline included as covariate.
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	2.8
	Confidence Interval	(2-Sided) 95%; -1.4 to 7.0
	Estimation Comments	[Not Specified]

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Inotuzumab Ozogamicin, Defined Investigator's Choice of Chemotherapy
	Comments	Social Functioning
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.0336
	Comments	[Not Specified]
	Method	Mixed Models Analysis
	Comments	Treatment, time, treatment-by-time interaction, and baseline included as covariate.
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	8.4
	Confidence Interval	(2-Sided) 95%; 0.7 to 16.1
	Estimation Comments	[Not Specified]

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Inotuzumab Ozogamicin, Defined Investigator's Choice of Chemotherapy
	Comments	Global Health Status
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.1572
	Comments	[Not Specified]
	Method	Mixed Models Analysis
	Comments	Treatment, time, treatment-by-time interaction, and baseline included as covariate.
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	4.3
	Confidence Interval	(2-Sided) 95%; -1.7 to 10.3
	Estimation Comments	[Not Specified]

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	Inotuzumab Ozogamicin, Defined Investigator's Choice of Chemotherapy
	Comments	Dyspnoea
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.1281
	Comments	[Not Specified]
	Method	Mixed Models Analysis
	Comments	Treatment, time, treatment-by-time interaction, and baseline included as covariate.
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-4.7
	Confidence Interval	(2-Sided) 95%; -10.8 to 1.4
	Estimation Comments	[Not Specified]

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	Inotuzumab Ozogamicin, Defined Investigator's Choice of Chemotherapy
	Comments	Insomnia
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.6207
	Comments	[Not Specified]
	Method	Mixed Models Analysis
	Comments	Treatment, time, treatment-by-time interaction, and baseline included as covariate.
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-1.7
	Confidence Interval	(2-Sided) 95%; -8.7 to 5.2
	Estimation Comments	[Not Specified]

Statistical Analysis 9

Statistical Analysis Overview	Comparison Group Selection	Inotuzumab Ozogamicin, Defined Investigator's Choice of Chemotherapy
	Comments	Appetite Loss
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.0193
	Comments	[Not Specified]
	Method	Mixed Models Analysis
	Comments	Treatment, time, treatment-by-time interaction, and baseline included as covariate.
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-8.7
	Confidence Interval	(2-Sided) 95%; -16.0 to -1.4
	Estimation Comments	[Not Specified]

Statistical Analysis 10

Statistical Analysis Overview	Comparison Group Selection	Inotuzumab Ozogamicin, Defined Investigator's Choice of Chemotherapy
	Comments	Constipation
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.6249
	Comments	[Not Specified]
	Method	Mixed Models Analysis
	Comments	Treatment, time, treatment-by-time interaction, and baseline included as covariate.
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	1.4
	Confidence Interval	(2-Sided) 95%; -4.4 to 7.3
	Estimation Comments	[Not Specified]

Statistical Analysis 11

Statistical Analysis Overview	Comparison Group Selection	Inotuzumab Ozogamicin, Defined Investigator's Choice of Chemotherapy
	Comments	Diarrhoea
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.1534
	Comments	[Not Specified]
	Method	Mixed Models Analysis
	Comments	Treatment, time, treatment-by-time interaction, and baseline included as covariate.
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-3.0
	Confidence Interval	(2-Sided) 95%; -7.2 to 1.1
	Estimation Comments	[Not Specified]

Statistical Analysis 12

Statistical Analysis Overview	Comparison Group Selection	Inotuzumab Ozogamicin, Defined Investigator's Choice of Chemotherapy
	Comments	Financial Difficulties
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.4915
	Comments	[Not Specified]
	Method	Mixed Models Analysis
	Comments	Treatment, time, treatment-by-time interaction, and baseline included as covariate.
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-2.5
	Confidence Interval	(2-Sided) 95%; -9.7 to 4.7
	Estimation Comments	[Not Specified]

Statistical Analysis 13

Statistical Analysis Overview	Comparison Group Selection	Inotuzumab Ozogamicin, Defined Investigator's Choice of Chemotherapy
	Comments	Fatigue
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.1789
	Comments	[Not Specified]
	Method	Mixed Models Analysis
	Comments	Treatment, time, treatment-by-time interaction, and baseline included as covariate.
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-4.4
	Confidence Interval	(2-Sided) 95%; -10.8 to 2.0
	Estimation Comments	[Not Specified]

Statistical Analysis 14

Statistical Analysis Overview	Comparison Group Selection	Inotuzumab Ozogamicin, Defined Investigator's Choice of Chemotherapy
	Comments	Nausea and Vomiting
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.4578
	Comments	[Not Specified]
	Method	Mixed Models Analysis
	Comments	Treatment, time, treatment-by-time interaction, and baseline included as covariate.
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-1.6
	Confidence Interval	(2-Sided) 95%; -6.0 to 2.7
	Estimation Comments	[Not Specified]

Statistical Analysis 15

Statistical Analysis Overview	Comparison Group Selection	Inotuzumab Ozogamicin, Defined Investigator's Choice of Chemotherapy
	Comments	Pain
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.8428
	Comments	[Not Specified]
	Method	Mixed Models Analysis
	Comments	Treatment, time, treatment-by-time interaction, and baseline included as covariate.
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-0.7
	Confidence Interval	(2-Sided) 95%; -7.3 to 6.0
	Estimation Comments	[Not Specified]

10. Secondary Outcome

Title	Change From Baseline in EuroQol 5 Dimension Health Questionnaire (EQ-5D) Index Score
Description	The EQ-5D self-report questionnaire is a standardized measure of health status developed by the EuroQoL Group. It consists of the EQ-5D descriptive system and a visual analogue scale (VAS), EQ-VAS. The EQ-5D descriptive system measures a participants' health state on 5 dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Each dimension has 3 levels, reflecting "no problems", "some problems", and "extreme problems". The EQ-VAS records the respondent's self-rated health on a scale from 0 (worst imaginable health state) to 100 (best imaginable health state); higher scores indicate a better health state. EQ-5D summary index is obtained with a formula that weights each level of the dimensions. The index-based score is interpreted along a continuum of 0 (death) to 1 (perfect health).
Time Frame	Day 1 of each cycle prior to dosing and EoT

Outcome Measure Data

Analysis Population Description

ITT population. Although only 143 participants were treated in the Defined Investigator's Choice of Chemotherapy arm, all 162 randomized participants were included in the ITT population.

Arm/Group Title	Inotuzumab Ozogamicin	Defined Investigator's Choice of Chemotherapy
Arm/Group Description:	Participants were treated with inotuzumab ozogamicin at a starting dose of 1.8 mg/m^2 (according to body surface area) per cycle with a divided-dose regimen using 3 weekly administrations. Participants received 0.8 mg/m^2/cycle on Week 1 (Day 1), followed by 0.5 mg/m^2 on Week 2 (Day 8) and Week 3 (Day 15) of a 21-day cycle, and administered as an intravenous infusion over 60 minutes. For participants who achieved a CR or CRi, or to allow recovery from toxicity, the length of Cycle 1 could be extended up to 28 days (ie, 1 week treatment-free interval starting on Day 21). For participants who achieved CR or CRi, the inotuzumab ozogamicin dose administered on Week 1 was reduced to 0.5 mg/m^2 (for a total cycle dose of 1.5 mg/m^2/cycle) for Cycles 2 through 6 (maximum number of cycles permitted). For Cycles 2 through 6, the cycle length was 28 days for all participants (regardless of remission status).	Participants received fludarabine, cytarabine, granulocyte-colony stimulating factor (FLAG), mitoxantrone + cytarabine (MXN/Ara-C), or high-dose cytarabine (HIDAC), according to the Investigator's choice.
Overall Number of Participants Analyzed	164	162
Mean (Standard Error); Unit of Measure: Score on a scale
Cycle 2, Day 1	0.00 (0.02)	0.02 (0.03)
Cycle 3, Day 1	0.01 (0.02)	-0.08 (0.08)
Cycle 4, Day 1	0.04 (0.03)	0.00 [1] (NA)
Cycle 5, Day 1	0.04 (0.04)	NA [2] (NA)
Cycle 6, Day 1	0.03 (0.04)	NA [2] (NA)
EoT	-0.01 (0.02)	-0.04 (0.02)

[1]

n=1

[2]

n=0

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Inotuzumab Ozogamicin, Defined Investigator's Choice of Chemotherapy
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.1710
	Comments	[Not Specified]
	Method	Mixed Models Analysis
	Comments	Treatment, time, treatment-by-time interaction, and baseline included as covariate.
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	0.03
	Confidence Interval	(2-Sided) 95%; -0.01 to 0.07
	Estimation Comments	[Not Specified]

11. Secondary Outcome

Title	Change From Baseline in EQ-5D VAS
Description	The EQ-5D self-report questionnaire is a standardized measure of health status developed by the EuroQoL Group. It consists of the EQ-5D descriptive system and a visual analogue scale (VAS), EQ-VAS. The EQ-5D descriptive system measures a participants' health state on 5 dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Each dimension has 3 levels, reflecting "no problems", "some problems", and "extreme problems". The EQ-VAS records the respondent's self-rated health on a scale from 0 (worst imaginable health state) to 100 (best imaginable health state); higher scores indicate a better health state.
Time Frame	Day 1 of each cycle prior to dosing and EoT

Outcome Measure Data

Analysis Population Description

ITT population. Although only 143 participants were treated in the Defined Investigator's Choice of Chemotherapy arm, all 162 randomized participants were included in the ITT population.

Arm/Group Title	Inotuzumab Ozogamicin	Defined Investigator's Choice of Chemotherapy
Arm/Group Description:	Participants were treated with inotuzumab ozogamicin at a starting dose of 1.8 mg/m^2 (according to body surface area) per cycle with a divided-dose regimen using 3 weekly administrations. Participants received 0.8 mg/m^2/cycle on Week 1 (Day 1), followed by 0.5 mg/m^2 on Week 2 (Day 8) and Week 3 (Day 15) of a 21-day cycle, and administered as an intravenous infusion over 60 minutes. For participants who achieved a CR or CRi, or to allow recovery from toxicity, the length of Cycle 1 could be extended up to 28 days (ie, 1 week treatment-free interval starting on Day 21). For participants who achieved CR or CRi, the inotuzumab ozogamicin dose administered on Week 1 was reduced to 0.5 mg/m^2 (for a total cycle dose of 1.5 mg/m^2/cycle) for Cycles 2 through 6 (maximum number of cycles permitted). For Cycles 2 through 6, the cycle length was 28 days for all participants (regardless of remission status).	Participants received fludarabine, cytarabine, granulocyte-colony stimulating factor (FLAG), mitoxantrone + cytarabine (MXN/Ara-C), or high-dose cytarabine (HIDAC), according to the Investigator's choice.
Overall Number of Participants Analyzed	164	162
Mean (Standard Error); Unit of Measure: Score on a scale
Cycle 2, Day 1	5.81 (2.14)	5.90 (4.21)
Cycle 3, Day 1	8.13 (2.53)	19.67 (17.80)
Cycle 4, Day 1	7.13 (3.37)	44.00 [1] (NA)
Cycle 5, Day 1	7.62 (4.43)	NA [2] (NA)
Cycle 6, Day 1	15.09 (9.14)	NA [2] (NA)
EoT	4.62 (2.38)	-0.52 (2.88)

[1]

n=1

[2]

n=0

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Inotuzumab Ozogamicin, Defined Investigator's Choice of Chemotherapy
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.1172
	Comments	[Not Specified]
	Method	Mixed Models Analysis
	Comments	Treatment, time, treatment-by-time interaction, and baseline included as covariate.
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	4.6
	Confidence Interval	(2-Sided) 95%; -1.2 to 10.4
	Estimation Comments	[Not Specified]

12. Secondary Outcome

Title	Percentage of Participants With Veno-Occlusive Liver Disease (VOD)/Sinusoidal Obstruction Syndrome (SOS) Following Post Study HSCT
Description	VOD/SOS was defined as the occurrence of 2 out of the following 3 clinical criteria: 1) total serum bilirubin level >34 micromoles per liter (μmol/L) (>2.0 milligrams per deciliter [mg/dL]), 2) an increase in liver size from baseline or development of right upper quadrant pain of liver origin and 3) sudden weight gain >2.5% (eg, within a 72 hour period) because of fluid accumulation in the weeks following infusion of study drug or chemotherapy, or HSCT conditioning/preparative therapy, or development of ascites not present at baseline following such exposures AND the absence of other explanations for these signs and symptoms, OR development of bilirubin elevation, weight gain, or hepatomegaly plus histologic abnormalities on liver biopsy demonstrating hepatocyte necrosis in zone 3 of the liver acinus, sinusoidal fibrosis, and centrilobular hemorrhage, with or without fibrosis of the terminal hepatic venules.
Time Frame	Up to 2 years from randomization

Outcome Measure Data

Analysis Population Description

Participants in the Safety population with post-study HSCT. A site visit in July 2017 (after clinical database lock), confirmed a fourth case of VOD/SOS occurred in the Defined Investigators Choice of Chemotherapy arm in March 2013 (approximately 3 months after the last dose).This was not entered on the CRF and therefore, is not included below.

Arm/Group Title	Inotuzumab Ozogamicin	Defined Investigator's Choice of Chemotherapy
Arm/Group Description:	Participants were treated with inotuzumab ozogamicin at a starting dose of 1.8 mg/m^2 (according to body surface area) per cycle with a divided-dose regimen using 3 weekly administrations. Participants received 0.8 mg/m^2/cycle on Week 1 (Day 1), followed by 0.5 mg/m^2 on Week 2 (Day 8) and Week 3 (Day 15) of a 21-day cycle, and administered as an intravenous infusion over 60 minutes. For participants who achieved a CR or CRi, or to allow recovery from toxicity, the length of Cycle 1 could be extended up to 28 days (ie, 1 week treatment-free interval starting on Day 21). For participants who achieved CR or CRi, the inotuzumab ozogamicin dose administered on Week 1 was reduced to 0.5 mg/m^2 (for a total cycle dose of 1.5 mg/m^2/cycle) for Cycles 2 through 6 (maximum number of cycles permitted). For Cycles 2 through 6, the cycle length was 28 days for all participants (regardless of remission status).	Participants received fludarabine, cytarabine, granulocyte-colony stimulating factor (FLAG), mitoxantrone + cytarabine (MXN/Ara-C), or high-dose cytarabine (HIDAC), according to the Investigator's choice.
Overall Number of Participants Analyzed	79	35
Measure Type: Number; Unit of Measure: Percentage of Participants
	22.8	8.6

Adverse Events

Time Frame	SAEs and non-serious AEs are summarized from Cycle 1 Day 1 up to 42 days after last dose, or any time after Cycle 1 Day1 (treatment-related).
Adverse Event Reporting Description	An event may appear as both an AE & SAE. However, what is presented are distinct events. An event may be categorized as serious in 1 participant & non-serious in another participant, or 1 participant may have experienced both a serious & non-serious event. Events were reported up to at least 28 days after last dose.
Arm/Group Title	Inotuzumab Ozogamicin	Defined Investigator's Choice of Chemotherapy
Arm/Group Description	Participants were treated with inotuzumab ozogamicin at a starting dose of 1.8 mg/m^2 (according to body surface area) per cycle with a divided-dose regimen using 3 weekly administrations. Participants received 0.8 mg/m^2/cycle on Week 1 (Day 1), followed by 0.5 mg/m^2 on Week 2 (Day 8) and Week 3 (Day 15) of a 21-day cycle, and administered as an intravenous infusion over 60 minutes. For participants who achieved a CR or CRi, or to allow recovery from toxicity, the length of Cycle 1 could be extended up to 28 days (ie, 1 week treatment-free interval starting on Day 21). For participants who achieved CR or CRi, the inotuzumab ozogamicin dose administered on Week 1 was reduced to 0.5 mg/m^2 (for a total cycle dose of 1.5 mg/m^2/cycle) for Cycles 2 through 6 (maximum number of cycles permitted). For Cycles 2 through 6, the cycle length was 28 days for all participants (regardless of remission status).	Participants received fludarabine, cytarabine, granulocyte-colony stimulating factor (FLAG), mitoxantrone + cytarabine (MXN/Ara-C), or high-dose cytarabine (HIDAC), according to the Investigator's choice.
All-Cause Mortality
	Inotuzumab Ozogamicin	Defined Investigator's Choice of Chemotherapy
	Affected / at Risk (%)	Affected / at Risk (%)
Total	--/--	--/--
Serious Adverse Events
	Inotuzumab Ozogamicin	Defined Investigator's Choice of Chemotherapy
	Affected / at Risk (%)	Affected / at Risk (%)
Total	85/164 (51.83%)	72/143 (50.35%)
Blood and lymphatic system disorders
Anaemia † 1	1/164 (0.61%)	0/143 (0.00%)
Febrile neutropenia † 1	19/164 (11.59%)	27/143 (18.88%)
Leukopenia † 1	1/164 (0.61%)	0/143 (0.00%)
Neutropenia † 1	2/164 (1.22%)	0/143 (0.00%)
Pancytopenia † 1	0/164 (0.00%)	2/143 (1.40%)
Thrombocytopenia † 1	1/164 (0.61%)	1/143 (0.70%)
Cardiac disorders
Acute coronary syndrome † 1	1/164 (0.61%)	0/143 (0.00%)
Atrial fibrillation † 1	1/164 (0.61%)	1/143 (0.70%)
Cardiac arrest † 1	1/164 (0.61%)	0/143 (0.00%)
Cardiac failure congestive † 1	1/164 (0.61%)	0/143 (0.00%)
Left ventricular dysfunction † 1	2/164 (1.22%)	0/143 (0.00%)
Myocardial infarction † 1	1/164 (0.61%)	0/143 (0.00%)
Pericarditis † 1	1/164 (0.61%)	0/143 (0.00%)
Eye disorders
Blindness unilateral † 1	1/164 (0.61%)	0/143 (0.00%)
Gastrointestinal disorders
Abdominal pain † 1	3/164 (1.83%)	1/143 (0.70%)
Abdominal pain lower † 1	1/164 (0.61%)	0/143 (0.00%)
Abdominal pain upper † 1	1/164 (0.61%)	0/143 (0.00%)
Ascites † 1	1/164 (0.61%)	0/143 (0.00%)
Colitis ischaemic † 1	1/164 (0.61%)	0/143 (0.00%)
Diarrhoea † 1	0/164 (0.00%)	1/143 (0.70%)
Dysphagia † 1	0/164 (0.00%)	1/143 (0.70%)
Gastritis haemorrhagic † 1	1/164 (0.61%)	0/143 (0.00%)
Gastrointestinal haemorrhage † 1	1/164 (0.61%)	0/143 (0.00%)
Ileal perforation † 1	0/164 (0.00%)	1/143 (0.70%)
Intestinal ischaemia † 1	1/164 (0.61%)	1/143 (0.70%)
Intra-abdominal haemorrhage † 1	1/164 (0.61%)	0/143 (0.00%)
Large intestinal ulcer † 1	1/164 (0.61%)	0/143 (0.00%)
Lower gastrointestinal haemorrhage † 1	1/164 (0.61%)	0/143 (0.00%)
Mesenteric haemorrhage † 1	1/164 (0.61%)	0/143 (0.00%)
Nausea † 1	2/164 (1.22%)	0/143 (0.00%)
Oesophageal stenosis † 1	0/164 (0.00%)	1/143 (0.70%)
Pancreatitis † 1	1/164 (0.61%)	0/143 (0.00%)
Proctalgia † 1	0/164 (0.00%)	1/143 (0.70%)
Small intestinal obstruction † 1	1/164 (0.61%)	0/143 (0.00%)
Stomatitis † 1	2/164 (1.22%)	1/143 (0.70%)
Upper gastrointestinal haemorrhage † 1	1/164 (0.61%)	0/143 (0.00%)
Vomiting † 1	1/164 (0.61%)	0/143 (0.00%)
General disorders
Asthenia † 1	3/164 (1.83%)	0/143 (0.00%)
Chest pain † 1	1/164 (0.61%)	0/143 (0.00%)
Disease progression † 1	8/164 (4.88%)	5/143 (3.50%)
Fatigue † 1	1/164 (0.61%)	0/143 (0.00%)
Mucosal inflammation † 1	0/164 (0.00%)	1/143 (0.70%)
Multiple organ dysfunction syndrome † 1	2/164 (1.22%)	2/143 (1.40%)
Pain † 1	1/164 (0.61%)	0/143 (0.00%)
Pyrexia † 1	5/164 (3.05%)	3/143 (2.10%)
Hepatobiliary disorders
Cholecystitis † 1	1/164 (0.61%)	0/143 (0.00%)
Hepatic vein thrombosis † 1	1/164 (0.61%)	0/143 (0.00%)
Hyperbilirubinaemia † 1	0/164 (0.00%)	3/143 (2.10%)
Venoocclusive liver disease † 1 [1]	23/164 (14.02%)	3/143 (2.10%)
Infections and infestations
Adenoviral upper respiratory infection † 1	1/164 (0.61%)	0/143 (0.00%)
Appendicitis † 1	0/164 (0.00%)	1/143 (0.70%)
Bacteraemia † 1	3/164 (1.83%)	1/143 (0.70%)
Bacterial infection † 1	0/164 (0.00%)	1/143 (0.70%)
Brain abscess † 1	1/164 (0.61%)	0/143 (0.00%)
Bronchopulmonary aspergillosis † 1	0/164 (0.00%)	1/143 (0.70%)
Candida infection † 1	1/164 (0.61%)	1/143 (0.70%)
Cellulitis † 1	1/164 (0.61%)	1/143 (0.70%)
Clostridium difficile colitis † 1	2/164 (1.22%)	1/143 (0.70%)
Clostridium difficile infection † 1	1/164 (0.61%)	0/143 (0.00%)
Corona virus infection † 1	1/164 (0.61%)	0/143 (0.00%)
Cytomegalovirus chorioretinitis † 1	0/164 (0.00%)	1/143 (0.70%)
Device related infection † 1	1/164 (0.61%)	0/143 (0.00%)
Diverticulitis † 1	1/164 (0.61%)	0/143 (0.00%)
Enteritis necroticans † 1	0/164 (0.00%)	1/143 (0.70%)
Enterococcal bacteraemia † 1	1/164 (0.61%)	0/143 (0.00%)
Enterococcal sepsis † 1	1/164 (0.61%)	0/143 (0.00%)
Escherichia bacteraemia † 1	2/164 (1.22%)	2/143 (1.40%)
Escherichia sepsis † 1	1/164 (0.61%)	2/143 (1.40%)
Febrile infection † 1	1/164 (0.61%)	0/143 (0.00%)
Fungaemia † 1	1/164 (0.61%)	0/143 (0.00%)
Fungal infection † 1	1/164 (0.61%)	0/143 (0.00%)
Herpes zoster † 1	1/164 (0.61%)	0/143 (0.00%)
Infection † 1	1/164 (0.61%)	0/143 (0.00%)
Influenza † 1	2/164 (1.22%)	0/143 (0.00%)
Klebsiella bacteraemia † 1	0/164 (0.00%)	1/143 (0.70%)
Klebsiella infection † 1	0/164 (0.00%)	1/143 (0.70%)
Liver abscess † 1	0/164 (0.00%)	1/143 (0.70%)
Lung infection † 1	1/164 (0.61%)	2/143 (1.40%)
Necrotising fasciitis fungal † 1	0/164 (0.00%)	1/143 (0.70%)
Neutropenic sepsis † 1	3/164 (1.83%)	4/143 (2.80%)
Parainfluenzae virus infection † 1	1/164 (0.61%)	0/143 (0.00%)
Pneumonia † 1	10/164 (6.10%)	0/143 (0.00%)
Pneumonia fungal † 1	0/164 (0.00%)	3/143 (2.10%)
Pneumonia pseudomonal † 1	0/164 (0.00%)	1/143 (0.70%)
Pseudomonal bacteraemia † 1	1/164 (0.61%)	2/143 (1.40%)
Pseudomonal sepsis † 1	1/164 (0.61%)	0/143 (0.00%)
Respiratory tract infection † 1	1/164 (0.61%)	0/143 (0.00%)
Sepsis † 1	4/164 (2.44%)	10/143 (6.99%)
Septic embolus † 1	1/164 (0.61%)	0/143 (0.00%)
Septic shock † 1	3/164 (1.83%)	3/143 (2.10%)
Serratia bacteraemia † 1	1/164 (0.61%)	0/143 (0.00%)
Sinusitis fungal † 1	1/164 (0.61%)	0/143 (0.00%)
Staphylococcal bacteraemia † 1	1/164 (0.61%)	1/143 (0.70%)
Staphylococcal sepsis † 1	2/164 (1.22%)	1/143 (0.70%)
Systemic candida † 1	1/164 (0.61%)	1/143 (0.70%)
Systemic mycosis † 1	0/164 (0.00%)	1/143 (0.70%)
Urinary tract infection † 1	1/164 (0.61%)	1/143 (0.70%)
Urinary tract infection fungal † 1	1/164 (0.61%)	0/143 (0.00%)
Mucormycosis † 1	1/164 (0.61%)	0/143 (0.00%)
Injury, poisoning and procedural complications
Fall † 1	1/164 (0.61%)	0/143 (0.00%)
Subdural haematoma † 1	1/164 (0.61%)	3/143 (2.10%)
Metabolism and nutrition disorders
Fluid overload † 1	1/164 (0.61%)	0/143 (0.00%)
Hyperglycaemia † 1	2/164 (1.22%)	0/143 (0.00%)
Lactic acidosis † 1	1/164 (0.61%)	0/143 (0.00%)
Tumour lysis syndrome † 1	2/164 (1.22%)	0/143 (0.00%)
Musculoskeletal and connective tissue disorders
Arthralgia † 1	1/164 (0.61%)	0/143 (0.00%)
Back pain † 1	2/164 (1.22%)	0/143 (0.00%)
Bone infarction † 1	1/164 (0.61%)	0/143 (0.00%)
Neck pain † 1	1/164 (0.61%)	0/143 (0.00%)
Osteonecrosis † 1	1/164 (0.61%)	0/143 (0.00%)
Nervous system disorders
Cerebrovascular accident † 1	0/164 (0.00%)	1/143 (0.70%)
Haemorrhage intracranial † 1	1/164 (0.61%)	1/143 (0.70%)
Headache † 1	2/164 (1.22%)	0/143 (0.00%)
Nervous system disorder † 1	1/164 (0.61%)	1/143 (0.70%)
Renal and urinary disorders
Acute kidney injury † 1	2/164 (1.22%)	0/143 (0.00%)
Haematuria † 1	1/164 (0.61%)	0/143 (0.00%)
Respiratory, thoracic and mediastinal disorders
Acute respiratory distress syndrome † 1	1/164 (0.61%)	0/143 (0.00%)
Epistaxis † 1	0/164 (0.00%)	1/143 (0.70%)
Pharyngeal stenosis † 1	0/164 (0.00%)	1/143 (0.70%)
Pleural effusion † 1	1/164 (0.61%)	0/143 (0.00%)
Respiratory failure † 1	2/164 (1.22%)	6/143 (4.20%)
Respiratory tract oedema † 1	0/164 (0.00%)	1/143 (0.70%)
Skin and subcutaneous tissue disorders
Dermatitis allergic † 1	1/164 (0.61%)	0/143 (0.00%)
Vascular disorders
Hypertension † 1	0/164 (0.00%)	1/143 (0.70%)
Hypotension † 1	0/164 (0.00%)	3/143 (2.10%)
Shock haemorrhagic † 1	1/164 (0.61%)	0/143 (0.00%)
Thrombophlebitis † 1	0/164 (0.00%)	1/143 (0.70%)
† Indicates events were collected by systematic assessment; 1 Term from vocabulary, MedDRA 18.1; [1] After clinical database lock, a fourth case of VOD/SOS was confirmed in the Defined Investigators Choice of Chemotherapy arm in March 2013 (approximately 3 months after last dose). This was not entered on the CRF and therefore, is not included below.
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	Inotuzumab Ozogamicin	Defined Investigator's Choice of Chemotherapy
	Affected / at Risk (%)	Affected / at Risk (%)
Total	159/164 (96.95%)	143/143 (100.00%)
Blood and lymphatic system disorders
Anaemia † 1	54/164 (32.93%)	79/143 (55.24%)
Febrile neutropenia † 1	27/164 (16.46%)	52/143 (36.36%)
Leukopenia † 1	47/164 (28.66%)	54/143 (37.76%)
Lymphopenia † 1	31/164 (18.90%)	36/143 (25.17%)
Neutropenia † 1	79/164 (48.17%)	66/143 (46.15%)
Thrombocytopenia † 1	80/164 (48.78%)	86/143 (60.14%)
Cardiac disorders
Tachycardia † 1	6/164 (3.66%)	16/143 (11.19%)
Eye disorders
Dry eye † 1	1/164 (0.61%)	8/143 (5.59%)
Gastrointestinal disorders
Abdominal distension † 1	10/164 (6.10%)	2/143 (1.40%)
Abdominal pain † 1	19/164 (11.59%)	26/143 (18.18%)
Abdominal pain upper † 1	11/164 (6.71%)	12/143 (8.39%)
Constipation † 1	28/164 (17.07%)	34/143 (23.78%)
Diarrhoea † 1	30/164 (18.29%)	55/143 (38.46%)
Dyspepsia † 1	3/164 (1.83%)	9/143 (6.29%)
Nausea † 1	52/164 (31.71%)	68/143 (47.55%)
Stomatitis † 1	5/164 (3.05%)	9/143 (6.29%)
Vomiting † 1	25/164 (15.24%)	35/143 (24.48%)
General disorders
Asthenia † 1	14/164 (8.54%)	14/143 (9.79%)
Chest pain † 1	3/164 (1.83%)	9/143 (6.29%)
Chills † 1	18/164 (10.98%)	17/143 (11.89%)
Fatigue † 1	41/164 (25.00%)	24/143 (16.78%)
Mucosal inflammation † 1	6/164 (3.66%)	19/143 (13.29%)
Oedema peripheral † 1	13/164 (7.93%)	13/143 (9.09%)
Pain † 1	12/164 (7.32%)	8/143 (5.59%)
Pyrexia † 1	49/164 (29.88%)	57/143 (39.86%)
Hepatobiliary disorders
Hyperbilirubinaemia † 1	35/164 (21.34%)	23/143 (16.08%)
Infections and infestations
Bacteraemia † 1	4/164 (2.44%)	13/143 (9.09%)
Pneumonia † 1	4/164 (2.44%)	12/143 (8.39%)
Sinusitis † 1	4/164 (2.44%)	8/143 (5.59%)
Injury, poisoning and procedural complications
Contusion † 1	10/164 (6.10%)	3/143 (2.10%)
Fall † 1	11/164 (6.71%)	4/143 (2.80%)
Investigations
Alanine aminotransferase increased † 1	25/164 (15.24%)	18/143 (12.59%)
Aspartate aminotransferase increased † 1	37/164 (22.56%)	16/143 (11.19%)
Blood alkaline phosphatase increased † 1	21/164 (12.80%)	10/143 (6.99%)
Gamma-glutamyltransferase increased † 1	35/164 (21.34%)	12/143 (8.39%)
Lipase increased † 1	15/164 (9.15%)	1/143 (0.70%)
White blood cell count decreased † 1	10/164 (6.10%)	9/143 (6.29%)
Metabolism and nutrition disorders
Decreased appetite † 1	19/164 (11.59%)	18/143 (12.59%)
Fluid overload † 1	2/164 (1.22%)	8/143 (5.59%)
Hyperglycaemia † 1	11/164 (6.71%)	12/143 (8.39%)
Hypoalbuminaemia † 1	10/164 (6.10%)	7/143 (4.90%)
Hypocalcaemia † 1	11/164 (6.71%)	15/143 (10.49%)
Hypokalaemia † 1	25/164 (15.24%)	33/143 (23.08%)
Hypomagnesaemia † 1	10/164 (6.10%)	12/143 (8.39%)
Hyponatraemia † 1	5/164 (3.05%)	9/143 (6.29%)
Hypophosphataemia † 1	9/164 (5.49%)	10/143 (6.99%)
Musculoskeletal and connective tissue disorders
Arthralgia † 1	9/164 (5.49%)	7/143 (4.90%)
Back pain † 1	16/164 (9.76%)	10/143 (6.99%)
Bone pain † 1	3/164 (1.83%)	10/143 (6.99%)
Pain in extremity † 1	13/164 (7.93%)	16/143 (11.19%)
Nervous system disorders
Dizziness † 1	12/164 (7.32%)	16/143 (11.19%)
Headache † 1	45/164 (27.44%)	38/143 (26.57%)
Psychiatric disorders
Anxiety † 1	8/164 (4.88%)	11/143 (7.69%)
Depression † 1	4/164 (2.44%)	9/143 (6.29%)
Insomnia † 1	24/164 (14.63%)	22/143 (15.38%)
Respiratory, thoracic and mediastinal disorders
Cough † 1	22/164 (13.41%)	23/143 (16.08%)
Dyspnoea † 1	10/164 (6.10%)	18/143 (12.59%)
Epistaxis † 1	24/164 (14.63%)	12/143 (8.39%)
Oropharyngeal pain † 1	6/164 (3.66%)	10/143 (6.99%)
Pleural effusion † 1	3/164 (1.83%)	8/143 (5.59%)
Skin and subcutaneous tissue disorders
Erythema † 1	7/164 (4.27%)	9/143 (6.29%)
Pruritus † 1	8/164 (4.88%)	10/143 (6.99%)
Rash † 1	14/164 (8.54%)	27/143 (18.88%)
Vascular disorders
Hypertension † 1	9/164 (5.49%)	8/143 (5.59%)
Hypotension † 1	12/164 (7.32%)	22/143 (15.38%)
† Indicates events were collected by systematic assessment; 1 Term from vocabulary, MedDRA 18.1

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days from the time submitted to the sponsor for review. Investigators will, on request, remove any previously undisclosed Confidential Information (other than the Study results themselves) before disclosure.

Results Point of Contact

• Name/Title: Pfizer ClinicalTrials.gov Call Center
• Organization: Pfizer, Inc.
• Phone: 1-800-718-1021
• EMail: ClinicalTrials.gov_Inquiries@pfizer.com

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Stelljes M, Advani AS, DeAngelo DJ, Wang T, Neuhof A, Vandendries E, Kantarjian H, Jabbour E. Time to First Subsequent Salvage Therapy in Patients With Relapsed/Refractory Acute Lymphoblastic Leukemia Treated With Inotuzumab Ozogamicin in the Phase III INO-VATE Trial. Clin Lymphoma Myeloma Leuk. 2022 Sep;22(9):e836-e843. doi: 10.1016/j.clml.2022.04.022. Epub 2022 Apr 27.

Shi Z, Zhu Y, Zhang J, Chen B. Monoclonal antibodies: new chance in the management of B-cell acute lymphoblastic leukemia. Hematology. 2022 Dec;27(1):642-652. doi: 10.1080/16078454.2022.2074704.

Kantarjian HM, Stock W, Cassaday RD, DeAngelo DJ, Jabbour E, O'Brien SM, Stelljes M, Wang T, Paccagnella ML, Nguyen K, Sleight B, Vandendries E, Neuhof A, Laird AD, Advani AS. Inotuzumab Ozogamicin for Relapsed/Refractory Acute Lymphoblastic Leukemia in the INO-VATE Trial: CD22 Pharmacodynamics, Efficacy, and Safety by Baseline CD22. Clin Cancer Res. 2021 May 15;27(10):2742-2754. doi: 10.1158/1078-0432.CCR-20-2399. Epub 2021 Feb 18.

Stock W, Martinelli G, Stelljes M, DeAngelo DJ, Gokbuget N, Advani AS, O'Brien S, Liedtke M, Merchant AA, Cassaday RD, Wang T, Zhang H, Vandendries E, Jabbour E, Marks DI, Kantarjian HM. Efficacy of inotuzumab ozogamicin in patients with Philadelphia chromosome-positive relapsed/refractory acute lymphoblastic leukemia. Cancer. 2021 Mar 15;127(6):905-913. doi: 10.1002/cncr.33321. Epub 2020 Nov 24.

DeAngelo DJ, Advani AS, Marks DI, Stelljes M, Liedtke M, Stock W, Gokbuget N, Jabbour E, Merchant A, Wang T, Vandendries E, Neuhof A, Kantarjian H, O'Brien S. Inotuzumab ozogamicin for relapsed/refractory acute lymphoblastic leukemia: outcomes by disease burden. Blood Cancer J. 2020 Aug 7;10(8):81. doi: 10.1038/s41408-020-00345-8.

Jabbour E, Gokbuget N, Advani A, Stelljes M, Stock W, Liedtke M, Martinelli G, O'Brien S, Wang T, Laird AD, Vandendries E, Neuhof A, Nguyen K, Dakappagari N, DeAngelo DJ, Kantarjian H. Impact of minimal residual disease status in patients with relapsed/refractory acute lymphoblastic leukemia treated with inotuzumab ozogamicin in the phase III INO-VATE trial. Leuk Res. 2020 Jan;88:106283. doi: 10.1016/j.leukres.2019.106283. Epub 2019 Nov 25.

Fujishima N, Uchida T, Onishi Y, Jung CW, Goh YT, Ando K, Wang MC, Ono C, Matsumizu M, Paccagnella ML, Sleight B, Vandendries E, Fujii Y, Hino M. Inotuzumab ozogamicin versus standard of care in Asian patients with relapsed/refractory acute lymphoblastic leukemia. Int J Hematol. 2019 Dec;110(6):709-722. doi: 10.1007/s12185-019-02749-0. Epub 2019 Nov 13.

Kantarjian HM, DeAngelo DJ, Stelljes M, Liedtke M, Stock W, Gokbuget N, O'Brien SM, Jabbour E, Wang T, Liang White J, Sleight B, Vandendries E, Advani AS. Inotuzumab ozogamicin versus standard of care in relapsed or refractory acute lymphoblastic leukemia: Final report and long-term survival follow-up from the randomized, phase 3 INO-VATE study. Cancer. 2019 Jul 15;125(14):2474-2487. doi: 10.1002/cncr.32116. Epub 2019 Mar 28.

Jabbour EJ, DeAngelo DJ, Stelljes M, Stock W, Liedtke M, Gokbuget N, O'Brien S, Wang T, Paccagnella ML, Sleight B, Vandendries E, Advani AS, Kantarjian HM. Efficacy and safety analysis by age cohort of inotuzumab ozogamicin in patients with relapsed or refractory acute lymphoblastic leukemia enrolled in INO-VATE. Cancer. 2018 Apr 15;124(8):1722-1732. doi: 10.1002/cncr.31249. Epub 2018 Jan 30.

Kebriaei P, Cutler C, de Lima M, Giralt S, Lee SJ, Marks D, Merchant A, Stock W, van Besien K, Stelljes M. Management of important adverse events associated with inotuzumab ozogamicin: expert panel review. Bone Marrow Transplant. 2018 Apr;53(4):449-456. doi: 10.1038/s41409-017-0019-y. Epub 2018 Jan 12.

Kantarjian HM, DeAngelo DJ, Advani AS, Stelljes M, Kebriaei P, Cassaday RD, Merchant AA, Fujishima N, Uchida T, Calbacho M, Ejduk AA, O'Brien SM, Jabbour EJ, Zhang H, Sleight BJ, Vandendries ER, Marks DI. Hepatic adverse event profile of inotuzumab ozogamicin in adult patients with relapsed or refractory acute lymphoblastic leukaemia: results from the open-label, randomised, phase 3 INO-VATE study. Lancet Haematol. 2017 Aug;4(8):e387-e398. doi: 10.1016/S2352-3026(17)30103-5. Epub 2017 Jul 4.

Kantarjian HM, DeAngelo DJ, Stelljes M, Martinelli G, Liedtke M, Stock W, Gokbuget N, O'Brien S, Wang K, Wang T, Paccagnella ML, Sleight B, Vandendries E, Advani AS. Inotuzumab Ozogamicin versus Standard Therapy for Acute Lymphoblastic Leukemia. N Engl J Med. 2016 Aug 25;375(8):740-53. doi: 10.1056/NEJMoa1509277. Epub 2016 Jun 12.

• Responsible Party: Pfizer
• ClinicalTrials.gov Identifier: NCT01564784
• Other Study ID Numbers: B1931022; 2011-005491-41 ( EudraCT Number )
• First Submitted: March 26, 2012
• First Posted: March 28, 2012
• Results First Submitted: March 2, 2017
• Results First Posted: January 17, 2018
• Last Update Posted: January 9, 2019