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

Acute Lymphoblastic Leukemia Clinical Trial

Official title:

AN OPEN-LABEL, RANDOMIZED PHASE 3 STUDY OF INOTUZUMAB OZOGAMICIN COMPARED TO A DEFINED INVESTIGATOR'S CHOICE IN ADULT PATIENTS WITH RELAPSED OR REFRACTORY CD22-POSITIVE ACUTE LYMPHOBLASTIC LEUKEMIA (ALL)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01564784
• Other study ID #: B1931022
• Secondary ID: 2011-005491-41
• Status: Completed
• Phase: Phase 3
• Start date: August 2, 2012
• Est. completion date: January 4, 2017

Study information

• Verified date: December 2018
• Source: Pfizer
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This study will compare the efficacy, in terms of complete responses and overall survival, of inotuzumab ozogamicin versus investigator's choice of chemotherapy.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 326
• Est. completion date: January 4, 2017
• Est. primary completion date: March 8, 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• CD22 expression

• Adequate liver and renal functions

Exclusion Criteria:

• Isolated extramedullary disease

• Active Central Nervous System [CNS] disease

Related Conditions & MeSH terms

• Acute Lymphoblastic Leukemia
• Leukemia
• Leukemia, Lymphoid
• Precursor Cell Lymphoblastic Leukemia-Lymphoma

Intervention

Drug:
• inotuzumab ozogamicin
Dose: inotuzumab ozogamicin 0.8-0.5 mg/m^2 IV, weekly, 3 times per cycle Cycle length: 21-28 days Total number of cycles: 6
• FLAG (fludarabine, cytarabine and G-CSF)
Dose: cytarabine 2.0 g/m^2/day IV days 1-6 fludarabine30 mg/m^2/day IV days 2-6 Cycle length: 28 days Total number of cycles: 4
• HIDAC (high dose cytarabine)
cytarabine 3 g/m^2 IV every 12 hours for up to 12 times
• cytarabine and mitoxantrone
mitoxantrone 12 mg/m^2 IV days 1-3 cytarabine 200 mg/m^2/day IV over 7 days cycle length: 15-20 days Total number of cycles: 4

Locations

Country	Name	City	State
Argentina	Sanatorio Allende	Cordoba
Australia	Royal Adelaide Hospital	Adelaide	South Australia
Australia	Eastern Clinical Research Unit, Box Hill Hospital	Box Hill	Victoria
Canada	Princess Margaret Cancer Centre	Toronto	Ontario
China	Beijing Chao-yang Hospital	Beijing
China	Peking University People's Hospital	Beijing
China	The 307th Hospital of PLA	Beijing
China	The first hospital of jilin university	Changchun	Jilin
China	Guangdong General Hospital	Guangzhou	Guangdong
China	Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences,	Tianjin
China	Henan Cancer Hostipal	Zhengzhou	Henan
Czechia	Interni Hematologicka a Onkologicka Klinika	Brno
Czechia	Fakultni Nemocnice Hradec Kralove	Hradec Kralove
Czechia	Fakultni nemocnice Kralovske Vinohrady	Praha 10
Finland	HUS-Kuvantaminen	Helsinki
Finland	HYKS/Hematologian klinikka	Helsinki
France	CHU de Dijon-Hopital d'Enfants-Service d'hematologie Clinique	Dijon
France	C.H.U. de Grenoble, Hopital Albert Michallon	Grenoble Cedex 09
France	Hopital Universitaire Andre Mignot	Le Chesnay Cedex
France	CHU Dupuytren	Limoges Cedex
France	Institut Paoli-Calmettes	Marseille
France	Hôpital Saint-Louis	Paris Cedex 10
France	Centre Hospitalier Lyon Sud	Pierre Benite Cedex
France	Institut de Cancérologie Lucien Neuwirth	Saint Priest en Jarez Cedex
France	Iuct - Oncopole	Toulouse Cedex 9
France	CHU Brabois- Service d'hematologie	Vandoeuvre-les-Nancy
Germany	Klinikum der Goethe Universitaet	Frankfurt
Germany	Universitaetsklinikum Heidelberg	Heidelberg
Germany	Universitätsklinikum Köln, Klinik I für Innere Medizin	Köln
Germany	Klinikum Rechts der Isar der TU München	Muenchen
Germany	Institut fuer klinische Radiologie	Muenster
Germany	Universitaetsklinikum Muenster	Muenster
Germany	Zentralapotheke des Universitaetsklinikums Muenster	Muenster	Nordrhein-westfalen
Hungary	Egyesitett Szent Istvan és Szent Laszlo Korhaz-Rendelointezet;	Budapest
Hungary	Debreceni Egyetem Orvos-es Egeszsegtudomanyi Centrum II. Belgyogyaszati Klinika	Debrecen
Italy	Istituto di Ematologia Seragnoli	Bologna
Italy	Azienda Ospedaliera Brotzu CTMO P.O. Businco	Cagliari	CA
Italy	Farmacia	Cagliari	CA
Italy	U.O. Radiodiagnostica	Cagliari	CA
Italy	A.O.U. Vittorio Emanuele di Catania-Ospedale Ferrarotto	Catania
Italy	Radiology (Radiology Only)	Catania
Italy	U.O. di Ematologia Dip. Medicine Specialistiche A.O.U. Arcispedale Sant'Anna	Cona, Ferrara
Italy	Clinica Ematologica	Genova
Italy	Pharmacy	Genova
Italy	Radiology Department	Genova
Italy	Radiology Department (Radiology ONLY)	Genova
Italy	U.O. Ematologia 1	Genova
Italy	IRST-Ematologia	Meldola (FC)	FC
Italy	S.C. Pharmacy	Milano
Italy	S.C. Radiology	Milano
Italy	SC Ematologia	Milano
Italy	A.O. San Gerardo - Farmacia	Monza
Italy	A.O. San Gerardo di Monza	Monza
Italy	AORN "A. Cardarelli"	Napoli
Italy	RAdiology Department (RAdiology only)	Napoli
Italy	Clinica Ematologica	Pavia
Italy	Radiologist Department	Ravenna
Italy	Servizio di Farmacia	Ravenna
Italy	U.O. Ematologia, Ospedale S. Maria delle Croci	Ravenna
Italy	Clinica Ematologica	Udine
Italy	Radiology (Radiology Only)	Udine
Japan	Akita University Hospital	Akita
Japan	National Cancer Center Hospital	Chuo-ku	Tokyo
Japan	National Hospital Organization Kyushu Cancer Center	Fukuoka
Japan	Tokai University Hospital	Kanagawa
Japan	Nagoya Daini Red Cross Hospital	Nagoya	Aichi
Japan	The Hospital of Hyogo College of Medicine	Nishinomiya-shi	Hyogo
Japan	Osaka City University Hospital	Osaka-city	Osaka
Japan	Tohoku University Hospital	Sendai	Miyagi
Korea, Republic of	Chonnam National University, Hwasun Hospital	Hwasun-Gun	Jeonnam
Korea, Republic of	Asan Medical Center	Seoul
Korea, Republic of	Samsung Medical Center	Seoul
Netherlands	Erasmus Medical Center	Rotterdam	South Holland
Netherlands	Erasmus Medical Center	Rotterdam	South Holland
Poland	Klinika Hematologii i Transplantologii	Gdansk
Poland	Oddzial Hematologii, Klinika Hematologii, Regionalny Osrodek Onkologiczny Wojewodzki Szpital	Lodz
Poland	Instytut Hematologii i Transfuzjologii, Klinika Hematologii	Warsaw
Poland	Dolnoslaskie Centrum Transplantacji Komorkowych z Krajowym Bankiem Dawcow Szpiku	Wroclaw
Singapore	National University Hospital/National University Cancer Institute Singapore (NCIS)	Singapore
Singapore	Singapore General Hospital	Singapore
Spain	Hospital Universitari Germans Trias i Pujol	Badalona	Barcelona
Spain	Hospital de la Santa Creu i Sant Pau(Nuevo Hospital)	Barcelona
Spain	Hospital Vall d'Hebron	Barcelona	Catalonia
Spain	Hospital General Universitario Gregorio Maranon	Madrid
Spain	Hospital Ramon y Cajal	Madrid
Spain	Hospital Universitario 12 de Octubre	Madrid
Spain	Hospital General Universitario Jose Maria Morales Meseguer	Murcia
Spain	Hospital Son Llatzer	Palma de Mallorca	Mallorca
Spain	Hospital Universitario de Salamanca	Salamanca	Castille AND LION
Spain	Hospital Universitario Virgen del Rocio	Sevilla
Spain	Hospital Clinico Universitario de Valencia	Valencia
Sweden	Universitetssjukhus Lund, Hematologkliniken	Lund
Sweden	Hematology Center	Stockholm
Taiwan	Chang Gung Medical Foundation, Kaohsiung Branch	Kaohsiung
Taiwan	National Taiwan University Hospital	Taipei
United Kingdom	Bristol Haematology and Oncology Centre	Bristol
United Kingdom	Castle Hill Hospital	Hull
United Kingdom	Department of Academic Oncology	London
United Kingdom	The Christie NHS Foundation Trust	Manchester
United Kingdom	Nottingham University Hospitals NHS Trust	Nottingham
United Kingdom	Churchill Hospital	Oxford
United Kingdom	Southampton General Hospital	Southampton	Hampshire
United States	University of New Mexico Comprehensive Cancer Center	Albuquerque	New Mexico
United States	UNM Cancer Center	Albuquerque	New Mexico
United States	University of Michigan Health System-	Ann Arbor	Michigan
United States	Blood and Marrow Transplant Group of Georgia	Atlanta	Georgia
United States	Emory University Hospital	Atlanta	Georgia
United States	Investigational Drug Service, Emory University Clinic	Atlanta	Georgia
United States	Northside Hospital	Atlanta	Georgia
United States	The Emory Clinic	Atlanta	Georgia
United States	Winship Cancer Institute, Emory University	Atlanta	Georgia
United States	Georgia Regents Medical Center Pharmacy, Georgia Regents University Cancer Center	Augusta	Georgia
United States	Georgia Regents University	Augusta	Georgia
United States	University of Colorado Cancer Center	Aurora	Colorado
United States	University of Colorado Hospital	Aurora	Colorado
United States	University of Colorado Hospital, Cancer Center Infusion Center	Aurora	Colorado
United States	Oncology Investigational Drug Service	Baltimore	Maryland
United States	The Sidney Kimmel Comprehensive Cancer Center	Baltimore	Maryland
United States	University of Maryland	Baltimore	Maryland
United States	Brigham and Women's Hospital	Boston	Massachusetts
United States	Dana-Farber Cancer Institute	Boston	Massachusetts
United States	Massachusetts General Hospital (MGH)	Boston	Massachusetts
United States	UNC Cancer Hospital Infusion Pharmacy	Chapel Hill	North Carolina
United States	UNC Hospitals - The University of North Carolina at Chapel Hill	Chapel Hill	North Carolina
United States	Hollings Cancer Center	Charleston	South Carolina
United States	MUSC Hospital	Charleston	South Carolina
United States	Northwestern Medical Faculty Foundation	Chicago	Illinois
United States	Northwestern Medicine Developmental Therapeutics Institute	Chicago	Illinois
United States	Northwestern Memorial Hospital	Chicago	Illinois
United States	The University of Chicago	Chicago	Illinois
United States	University of Chicago Medical Center, Dept. of Pharmacy	Chicago	Illinois
United States	University of Cincinnati Medical Center	Cincinnati	Ohio
United States	Cleveland Clinic Foundation	Cleveland	Ohio
United States	University Hospitals of Cleveland	Cleveland	Ohio
United States	Baylor Charles A. Sammons Cancer Center	Dallas	Texas
United States	Baylor University Medical Center	Dallas	Texas
United States	Parkland Health and Hospital System	Dallas	Texas
United States	University of Texas Southwestern Universtiy Hospital - William P Clements Jr.	Dallas	Texas
United States	UT Southwestern Medical Center at Dallas	Dallas	Texas
United States	UT Southwestern University Hospital- Zale Lipshy	Dallas	Texas
United States	Karmanos Cancer Institute	Detroit	Michigan
United States	Karmanos Cancer Institute Weisberg Cancer Treatment Center	Farmington Hills	Michigan
United States	Hackensack University Medical Center	Hackensack	New Jersey
United States	John Theurer Cancer Center at Hackensack University Medical Center	Hackensack	New Jersey
United States	IDS-investigational drug pharmacy Penn State Milton S. Hershey Medical Center	Hershey	Pennsylvania
United States	Penn State Milton S. Hershey Medical Center,	Hershey	Pennsylvania
United States	The University of Texas MD Anderson Cancer Center	Houston	Texas
United States	University of Iowa Hospitals and Clinics	Iowa City	Iowa
United States	University of Kansas Hospital	Kansas City	Kansas
United States	Investigational Drug Services - UC San Diego Moores Cancer Center	La Jolla	California
United States	UC San Diego Medical Center - La Jolla	La Jolla	California
United States	UC San Diego Moores Cancer Center	La Jolla	California
United States	Monter Cancer Center	Lake Success	New York
United States	Children's Center for Cancer and Blood Diseases, Childrens Hospital Los Angeles	Los Angeles	California
United States	Keck Hospital of USC	Los Angeles	California
United States	LAC+USC Medical Center	Los Angeles	California
United States	UCLA Drug Information/Investigation Drug	Los Angeles	California
United States	UCLA Hematology/Oncology Clinic	Los Angeles	California
United States	UCLA Ronald Reagan Medical Center	Los Angeles	California
United States	UCLA Rrmc	Los Angeles	California
United States	USC Norris Comprehensive Cancer Center	Los Angeles	California
United States	USC/Norris Comprehensive Cancer Center	Los Angeles	California
United States	USC/Norris Comprehensive Cancer Center / Investigational Drug Services	Los Angeles	California
United States	Norton Cancer Institute	Louisville	Kentucky
United States	Norton Cancer Institute, Suburban	Louisville	Kentucky
United States	North Shore University Hospital	Manhasset	New York
United States	Miami Children's Hospital	Miami	Florida
United States	West Virginia University Hospitals	Morgantown	West Virginia
United States	West Virginia University Hospitals Pharmaceutical Services	Morgantown	West Virginia
United States	Rutgers Cancer Institute of New Jersey	New Brunswick	New Jersey
United States	Yale-New Haven Hospital & Smilow Cancer Center	New Haven	Connecticut
United States	New York Presbyterian Hospital-Weill Cornell Medical College	New York	New York
United States	NewYork-Presbyterian Hospital	New York	New York
United States	Weill Cornell Medical College - New York-Presbyterian Hospital	New York	New York
United States	OU Medical Center Presbyterian Tower	Oklahoma City	Oklahoma
United States	Stephenson Cancer Center	Oklahoma City	Oklahoma
United States	Children's Hospital of Orange County	Orange	California
United States	UC Irvine Medical Center	Orange	California
United States	UC Irvine Medical Center	Orange	California
United States	MD Anderson Cancer Center Orlando	Orlando	Florida
United States	MD Anderson Cancer Center Orlando - 5th Floor Investigational Pharmacy	Orlando	Florida
United States	Orlando Heart Health Institute	Orlando	Florida
United States	Orlando Regional Medical Center	Orlando	Florida
United States	Freidenrich Center for Translational Research (CTRU), Stanford University	Palo Alto	California
United States	University of Rochester Medical Center	Rochester	New York
United States	LDS Hospital	Salt Lake City	Utah
United States	UC San Diego Medical Center - Hillcrest	San Diego	California
United States	Seattle Cancer Care Alliance	Seattle	Washington
United States	University of Washington	Seattle	Washington
United States	Martha Hamilton, Investigational Drug Services, Dept of Pharmacy	Stanford	California
United States	Stanford Cancer Institute	Stanford	California
United States	Stanford University Hospital and Clinics	Stanford	California
United States	Division of Hematology/Oncology, Stony Brook University Hospital	Stony Brook	New York
United States	Stony Brook University Medical Center	Stony Brook	New York
United States	Stony Brook University Medical Center	Stony Brook	New York
United States	Stony Brook University Medical Center, The Cancer Center	Stony Brook	New York
United States	University of Kansas Cancer Center	Westwood	Kansas
United States	Wake Forest Baptist Health	Winston-Salem	North Carolina

Sponsors (2)

Lead Sponsor	Collaborator
Pfizer	UCB Pharma

Countries where clinical trial is conducted

United States,  Argentina,  Australia,  Canada,  China,  Czechia,  Finland,  France,  Germany,  Hungary,  Italy,  Japan,  Korea, Republic of,  Netherlands,  Poland,  Singapore,  Spain,  Sweden,  Taiwan,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of Participants With Hematologic Remission (Complete Remission [CR]/Complete Remission With Incomplete Hematologic Recovery [CRi]) as Assessed by the Endpoint Adjudication Committee (EAC)	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.	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
Primary	Overall Survival (OS)	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.	Up to 5 years after randomization or 2 years from randomization of the last participant, whichever occurs first.
Secondary	Duration of Remission (DoR) for Participants Who Achieved CR/CRi (Per Investigator Assessment)	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.	Up to 2 years from randomization
Secondary	Progression-Free Survival (PFS)	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.	Up to 2 years from randomization
Secondary	Percentage of Participants Who Had a Hematopoietic Stem-Cell Transplant (HSCT)	HSCT rate was defined as the percentage of participants who underwent SCT following treatment with inotuzumab ozogamicin or Investigator's choice of chemotherapy.	Up to 19 weeks from last dose
Secondary	Percentage of Participants Achieving MRD Negativity (Based on Central Laboratory Analysis) in Participants Achieving a CR/CRi (Per EAC Assessment)	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.	Up to approximately 4 weeks (EoT) from last dose of study drug
Secondary	Cytogenetic Status (Based on Local Laboratory Analysis) of Participants With CR/CRi (Per EAC Assessment)	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.	Up to approximately 4 weeks (EoT) from last dose of study drug
Secondary	Maximum Observed Inotuzumab Ozogamicin Serum Concentration (Cmax) and Pre-Dose Inotuzumab Ozogamicin Serum Concentration (Ctrough) Following Single and Multiple Dosing	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).	Days 1, 4, 8, and 15 of Cycle 1, Days 1 and 8 of Cycle 2 and Day 1 of Cycle 4
Secondary	Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire, Core 30 (EORTC QLQ-C30) Score	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.	Day 1 of each cycle prior to dosing and EoT
Secondary	Change From Baseline in EuroQol 5 Dimension Health Questionnaire (EQ-5D) Index Score	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).	Day 1 of each cycle prior to dosing and EoT
Secondary	Change From Baseline in EQ-5D VAS	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.	Day 1 of each cycle prior to dosing and EoT
Secondary	Percentage of Participants With Veno-Occlusive Liver Disease (VOD)/Sinusoidal Obstruction Syndrome (SOS) Following Post Study HSCT	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.	Up to 2 years from randomization