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

Sponsor
Pfizer (Industry)
Overall Status
Completed
CT.gov ID
NCT01564784
Collaborator
UCB Pharma (Industry)
326
Enrollment
198
Locations
2
Arms
53.1
Actual Duration (Months)
1.6
Patients Per Site
0
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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

Condition or Disease Intervention/Treatment Phase
  • Drug: inotuzumab ozogamicin
  • Drug: FLAG (fludarabine, cytarabine and G-CSF)
  • Drug: HIDAC (high dose cytarabine)
  • Drug: cytarabine and mitoxantrone
 Phase 3

Study Design

Study Type:
Interventional
Actual Enrollment :
326 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
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)
Actual Study Start Date :
Aug 2, 2012
Actual Primary Completion Date :
Mar 8, 2016
Actual Study Completion Date :
Jan 4, 2017

Arms and Interventions

Arm Intervention/Treatment
Experimental: Arm A

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
Active Comparator: Arm B

Drug: 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

Drug: HIDAC (high dose cytarabine)
cytarabine 3 g/m^2 IV every 12 hours for up to 12 times

Drug: 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

Outcome Measures

Primary Outcome Measures

  1. Percentage of Participants With Hematologic Remission (Complete Remission [CR]/Complete Remission With Incomplete Hematologic Recovery [CRi]) as Assessed by the Endpoint Adjudication Committee (EAC) [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]

    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.

  2. Overall Survival (OS) [Up to 5 years after randomization or 2 years from randomization of the last participant, whichever occurs first.]

    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.

Secondary Outcome Measures

  1. Duration of Remission (DoR) for Participants Who Achieved CR/CRi (Per Investigator Assessment) [Up to 2 years from randomization]

    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.

  2. Progression-Free Survival (PFS) [Up to 2 years from randomization]

    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.

  3. Percentage of Participants Who Had a Hematopoietic Stem-Cell Transplant (HSCT) [Up to 19 weeks from last dose]

    HSCT rate was defined as the percentage of participants who underwent SCT following treatment with inotuzumab ozogamicin or Investigator's choice of chemotherapy.

  4. Percentage of Participants Achieving MRD Negativity (Based on Central Laboratory Analysis) in Participants Achieving a CR/CRi (Per EAC Assessment) [Up to approximately 4 weeks (EoT) from last dose of study drug]

    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.

  5. Cytogenetic Status (Based on Local Laboratory Analysis) of Participants With CR/CRi (Per EAC Assessment) [Up to approximately 4 weeks (EoT) from last dose of study drug]

    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.

  6. Maximum Observed Inotuzumab Ozogamicin Serum Concentration (Cmax) and Pre-Dose Inotuzumab Ozogamicin Serum Concentration (Ctrough) Following Single and Multiple Dosing [Days 1, 4, 8, and 15 of Cycle 1, Days 1 and 8 of Cycle 2 and Day 1 of Cycle 4]

    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).

  7. Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire, Core 30 (EORTC QLQ-C30) Score [Day 1 of each cycle prior to dosing and EoT]

    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.

  8. Change From Baseline in EuroQol 5 Dimension Health Questionnaire (EQ-5D) Index Score [Day 1 of each cycle prior to dosing and EoT]

    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).

  9. Change From Baseline in EQ-5D VAS [Day 1 of each cycle prior to dosing and EoT]

    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.

  10. Percentage of Participants With Veno-Occlusive Liver Disease (VOD)/Sinusoidal Obstruction Syndrome (SOS) Following Post Study HSCT [Up to 2 years from randomization]

    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.

Eligibility Criteria

Criteria

Ages Eligible for Study:
18 Years and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:

  • CD22 expression

  • Adequate liver and renal functions

Exclusion Criteria:

  • Isolated extramedullary disease

  • Active Central Nervous System [CNS] disease

Contacts and Locations

Locations

Site City State Country Postal Code
1 Investigational Drug Services - UC San Diego Moores Cancer Center La Jolla California United States 92037-0845
2 UC San Diego Medical Center - La Jolla La Jolla California United States 92037
3 UC San Diego Moores Cancer Center La Jolla California United States 92093-0698
4 Children's Center for Cancer and Blood Diseases, Childrens Hospital Los Angeles Los Angeles California United States 90027
5 Keck Hospital of USC Los Angeles California United States 90033
6 LAC+USC Medical Center Los Angeles California United States 90033
7 USC Norris Comprehensive Cancer Center Los Angeles California United States 90033
8 USC/Norris Comprehensive Cancer Center / Investigational Drug Services Los Angeles California United States 90033
9 USC/Norris Comprehensive Cancer Center Los Angeles California United States 90033
10 UCLA Drug Information/Investigation Drug Los Angeles California United States 90095
11 UCLA Hematology/Oncology Clinic Los Angeles California United States 90095
12 UCLA Ronald Reagan Medical Center Los Angeles California United States 90095
13 UCLA Rrmc Los Angeles California United States 90095
14 UC Irvine Medical Center Orange California United States 92868-3201
15 Children's Hospital of Orange County Orange California United States 92868
16 UC Irvine Medical Center Orange California United States 92868
17 Freidenrich Center for Translational Research (CTRU), Stanford University Palo Alto California United States 94304
18 UC San Diego Medical Center - Hillcrest San Diego California United States 92103
19 Martha Hamilton, Investigational Drug Services, Dept of Pharmacy Stanford California United States 94305
20 Stanford Cancer Institute Stanford California United States 94305
21 Stanford University Hospital and Clinics Stanford California United States 94305
22 University of Colorado Cancer Center Aurora Colorado United States 80045
23 University of Colorado Hospital, Cancer Center Infusion Center Aurora Colorado United States 80045
24 University of Colorado Hospital Aurora Colorado United States 80045
25 Yale-New Haven Hospital & Smilow Cancer Center New Haven Connecticut United States 06510
26 Miami Children's Hospital Miami Florida United States 33155
27 MD Anderson Cancer Center Orlando - 5th Floor Investigational Pharmacy Orlando Florida United States 32806
28 MD Anderson Cancer Center Orlando Orlando Florida United States 32806
29 Orlando Heart Health Institute Orlando Florida United States 32806
30 Orlando Regional Medical Center Orlando Florida United States 32806
31 Emory University Hospital Atlanta Georgia United States 30322
32 Investigational Drug Service, Emory University Clinic Atlanta Georgia United States 30322
33 The Emory Clinic Atlanta Georgia United States 30322
34 Winship Cancer Institute, Emory University Atlanta Georgia United States 30322
35 Blood and Marrow Transplant Group of Georgia Atlanta Georgia United States 30342
36 Northside Hospital Atlanta Georgia United States 30342
37 Georgia Regents Medical Center Pharmacy, Georgia Regents University Cancer Center Augusta Georgia United States 30912
38 Georgia Regents University Augusta Georgia United States 30912
39 Northwestern Medical Faculty Foundation Chicago Illinois United States 60611
40 Northwestern Medicine Developmental Therapeutics Institute Chicago Illinois United States 60611
41 Northwestern Memorial Hospital Chicago Illinois United States 60611
42 The University of Chicago Chicago Illinois United States 60637
43 University of Chicago Medical Center, Dept. of Pharmacy Chicago Illinois United States 60637
44 University of Iowa Hospitals and Clinics Iowa City Iowa United States 52242
45 University of Kansas Hospital Kansas City Kansas United States 66160
46 University of Kansas Cancer Center Westwood Kansas United States 66205
47 Norton Cancer Institute Louisville Kentucky United States 40202
48 Norton Cancer Institute, Suburban Louisville Kentucky United States 40207
49 University of Maryland Baltimore Maryland United States 21201
50 Oncology Investigational Drug Service Baltimore Maryland United States 21231-2410
51 The Sidney Kimmel Comprehensive Cancer Center Baltimore Maryland United States 21231-2410
52 Massachusetts General Hospital (MGH) Boston Massachusetts United States 02114
53 Brigham and Women's Hospital Boston Massachusetts United States 02115
54 Dana-Farber Cancer Institute Boston Massachusetts United States 02215
55 University of Michigan Health System- Ann Arbor Michigan United States 48109
56 Karmanos Cancer Institute Detroit Michigan United States 48201
57 Karmanos Cancer Institute Weisberg Cancer Treatment Center Farmington Hills Michigan United States 48334
58 Hackensack University Medical Center Hackensack New Jersey United States 07601
59 John Theurer Cancer Center at Hackensack University Medical Center Hackensack New Jersey United States 07601
60 Rutgers Cancer Institute of New Jersey New Brunswick New Jersey United States 08903
61 University of New Mexico Comprehensive Cancer Center Albuquerque New Mexico United States 87131-0001
62 UNM Cancer Center Albuquerque New Mexico United States 87131
63 Monter Cancer Center Lake Success New York United States 11042
64 North Shore University Hospital Manhasset New York United States 11030
65 New York Presbyterian Hospital-Weill Cornell Medical College New York New York United States 10021
66 NewYork-Presbyterian Hospital New York New York United States 10065
67 Weill Cornell Medical College - New York-Presbyterian Hospital New York New York United States 10065
68 University of Rochester Medical Center Rochester New York United States 14642
69 Stony Brook University Medical Center Stony Brook New York United States 11794-7007
70 Stony Brook University Medical Center, The Cancer Center Stony Brook New York United States 11794-9447
71 Division of Hematology/Oncology, Stony Brook University Hospital Stony Brook New York United States 11794
72 Stony Brook University Medical Center Stony Brook New York United States 11794
73 UNC Cancer Hospital Infusion Pharmacy Chapel Hill North Carolina United States 27514
74 UNC Hospitals - The University of North Carolina at Chapel Hill Chapel Hill North Carolina United States 27599-7600
75 Wake Forest Baptist Health Winston-Salem North Carolina United States 27157
76 University of Cincinnati Medical Center Cincinnati Ohio United States 45219
77 University Hospitals of Cleveland Cleveland Ohio United States 44106
78 Cleveland Clinic Foundation Cleveland Ohio United States 44195
79 OU Medical Center Presbyterian Tower Oklahoma City Oklahoma United States 73104
80 Stephenson Cancer Center Oklahoma City Oklahoma United States 73104
81 IDS-investigational drug pharmacy Penn State Milton S. Hershey Medical Center Hershey Pennsylvania United States 17033
82 Penn State Milton S. Hershey Medical Center, Hershey Pennsylvania United States 17033
83 Hollings Cancer Center Charleston South Carolina United States 29425
84 MUSC Hospital Charleston South Carolina United States 29425
85 Parkland Health and Hospital System Dallas Texas United States 75235
86 Baylor Charles A. Sammons Cancer Center Dallas Texas United States 75246
87 Baylor University Medical Center Dallas Texas United States 75246
88 University of Texas Southwestern Universtiy Hospital - William P Clements Jr. Dallas Texas United States 75390
89 UT Southwestern Medical Center at Dallas Dallas Texas United States 75390
90 UT Southwestern University Hospital- Zale Lipshy Dallas Texas United States 75390
91 The University of Texas MD Anderson Cancer Center Houston Texas United States 77030
92 LDS Hospital Salt Lake City Utah United States 84143
93 Seattle Cancer Care Alliance Seattle Washington United States 98109
94 University of Washington Seattle Washington United States 98195
95 West Virginia University Hospitals Pharmaceutical Services Morgantown West Virginia United States 26506
96 West Virginia University Hospitals Morgantown West Virginia United States 26506
97 Sanatorio Allende Cordoba Argentina 5000
98 Royal Adelaide Hospital Adelaide South Australia Australia 5000
99 Eastern Clinical Research Unit, Box Hill Hospital Box Hill Victoria Australia 3128
100 Princess Margaret Cancer Centre Toronto Ontario Canada M5G 2M9
101 Guangdong General Hospital Guangzhou Guangdong China 510080
102 Henan Cancer Hostipal Zhengzhou Henan China 450008
103 The first hospital of jilin university Changchun Jilin China 130021
104 Beijing Chao-yang Hospital Beijing China 100020
105 Peking University People's Hospital Beijing China 100044
106 The 307th Hospital of PLA Beijing China 100071
107 Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences, Tianjin China 300020
108 Interni Hematologicka a Onkologicka Klinika Brno Czechia 62500
109 Fakultni Nemocnice Hradec Kralove Hradec Kralove Czechia 50005
110 Fakultni nemocnice Kralovske Vinohrady Praha 10 Czechia 10034
111 HUS-Kuvantaminen Helsinki Finland 00290
112 HYKS/Hematologian klinikka Helsinki Finland 00290
113 CHU de Dijon-Hopital d'Enfants-Service d'hematologie Clinique Dijon France 21000
114 C.H.U. de Grenoble, Hopital Albert Michallon Grenoble Cedex 09 France 38043
115 Hopital Universitaire Andre Mignot Le Chesnay Cedex France 78157
116 CHU Dupuytren Limoges Cedex France 87042
117 Institut Paoli-Calmettes Marseille France 13009
118 Hôpital Saint-Louis Paris Cedex 10 France 75475
119 Centre Hospitalier Lyon Sud Pierre Benite Cedex France 69495
120 Institut de Cancérologie Lucien Neuwirth Saint Priest en Jarez Cedex France 42271
121 Iuct - Oncopole Toulouse Cedex 9 France 31059
122 CHU Brabois- Service d'hematologie Vandoeuvre-les-Nancy France 54511
123 Zentralapotheke des Universitaetsklinikums Muenster Muenster Nordrhein-westfalen Germany 48149
124 Klinikum der Goethe Universitaet Frankfurt Germany 60590
125 Universitaetsklinikum Heidelberg Heidelberg Germany 69120
126 Universitätsklinikum Köln, Klinik I für Innere Medizin Köln Germany 50937
127 Klinikum Rechts der Isar der TU München Muenchen Germany 81675
128 Institut fuer klinische Radiologie Muenster Germany 48149
129 Universitaetsklinikum Muenster Muenster Germany 48149
130 Egyesitett Szent Istvan és Szent Laszlo Korhaz-Rendelointezet; Budapest Hungary 1097
131 Debreceni Egyetem Orvos-es Egeszsegtudomanyi Centrum II. Belgyogyaszati Klinika Debrecen Hungary 4032
132 Azienda Ospedaliera Brotzu CTMO P.O. Businco Cagliari CA Italy 09121
133 Farmacia Cagliari CA Italy 09121
134 U.O. Radiodiagnostica Cagliari CA Italy 09121
135 IRST-Ematologia Meldola (FC) FC Italy 47014
136 Istituto di Ematologia Seragnoli Bologna Italy 40138
137 A.O.U. Vittorio Emanuele di Catania-Ospedale Ferrarotto Catania Italy 95124
138 Radiology (Radiology Only) Catania Italy 95124
139 U.O. di Ematologia Dip. Medicine Specialistiche A.O.U. Arcispedale Sant'Anna Cona, Ferrara Italy 44124
140 Clinica Ematologica Genova Italy 16132
141 Pharmacy Genova Italy 16132
142 Radiology Department (Radiology ONLY) Genova Italy 16132
143 Radiology Department Genova Italy 16132
144 U.O. Ematologia 1 Genova Italy 16132
145 S.C. Pharmacy Milano Italy 20162
146 S.C. Radiology Milano Italy 20162
147 SC Ematologia Milano Italy 20162
148 A.O. San Gerardo - Farmacia Monza Italy 20900
149 A.O. San Gerardo di Monza Monza Italy 20900
150 AORN "A. Cardarelli" Napoli Italy 80131
151 RAdiology Department (RAdiology only) Napoli Italy 80131
152 Clinica Ematologica Pavia Italy 27100
153 Radiologist Department Ravenna Italy 48121
154 Servizio di Farmacia Ravenna Italy 48121
155 U.O. Ematologia, Ospedale S. Maria delle Croci Ravenna Italy 48121
156 Clinica Ematologica Udine Italy 33100
157 Radiology (Radiology Only) Udine Italy 33100
158 Nagoya Daini Red Cross Hospital Nagoya Aichi Japan 4668650
159 The Hospital of Hyogo College of Medicine Nishinomiya-shi Hyogo Japan 6638501
160 Tohoku University Hospital Sendai Miyagi Japan 9808574
161 Osaka City University Hospital Osaka-city Osaka Japan 5458586
162 National Cancer Center Hospital Chuo-ku Tokyo Japan 1040045
163 Akita University Hospital Akita Japan 010-8543
164 National Hospital Organization Kyushu Cancer Center Fukuoka Japan 8111395
165 Tokai University Hospital Kanagawa Japan 259-1193
166 Chonnam National University, Hwasun Hospital Hwasun-Gun Jeonnam Korea, Republic of 519-763
167 Asan Medical Center Seoul Korea, Republic of 05505
168 Samsung Medical Center Seoul Korea, Republic of 135 710
169 Erasmus Medical Center Rotterdam South Holland Netherlands 3015 CE
170 Erasmus Medical Center Rotterdam South Holland Netherlands 3075 EA
171 Klinika Hematologii i Transplantologii Gdansk Poland 80-952
172 Oddzial Hematologii, Klinika Hematologii, Regionalny Osrodek Onkologiczny Wojewodzki Szpital Lodz Poland 93510
173 Instytut Hematologii i Transfuzjologii, Klinika Hematologii Warsaw Poland 02-776
174 Dolnoslaskie Centrum Transplantacji Komorkowych z Krajowym Bankiem Dawcow Szpiku Wroclaw Poland 53-439
175 National University Hospital/National University Cancer Institute Singapore (NCIS) Singapore Singapore 119228
176 Singapore General Hospital Singapore Singapore 169608
177 Hospital Universitari Germans Trias i Pujol Badalona Barcelona Spain 08916
178 Hospital Universitario de Salamanca Salamanca Castille AND LION Spain 37007
179 Hospital Vall d'Hebron Barcelona Catalonia Spain 08035
180 Hospital Son Llatzer Palma de Mallorca Mallorca Spain 07198
181 Hospital de la Santa Creu i Sant Pau(Nuevo Hospital) Barcelona Spain 08025
182 Hospital General Universitario Gregorio Maranon Madrid Spain 28007
183 Hospital Ramon y Cajal Madrid Spain 28034
184 Hospital Universitario 12 de Octubre Madrid Spain 28041
185 Hospital General Universitario Jose Maria Morales Meseguer Murcia Spain 30008
186 Hospital Universitario Virgen del Rocio Sevilla Spain 41013
187 Hospital Clinico Universitario de Valencia Valencia Spain 46010
188 Universitetssjukhus Lund, Hematologkliniken Lund Sweden 221 85
189 Hematology Center Stockholm Sweden 17176
190 Chang Gung Medical Foundation, Kaohsiung Branch Kaohsiung Taiwan 83301
191 National Taiwan University Hospital Taipei Taiwan 10002
192 Southampton General Hospital Southampton Hampshire United Kingdom SO16 6YD
193 Bristol Haematology and Oncology Centre Bristol United Kingdom BS2 8ED
194 Castle Hill Hospital Hull United Kingdom HU16 5JQ
195 Department of Academic Oncology London United Kingdom NW3 2QG
196 The Christie NHS Foundation Trust Manchester United Kingdom M20 4BX
197 Nottingham University Hospitals NHS Trust Nottingham United Kingdom NG5 1PB
198 Churchill Hospital Oxford United Kingdom OX3 7LJ

Sponsors and Collaborators

  • Pfizer
  • UCB Pharma

Investigators

  • Study Director: Pfizer CT.gov Call Center, Pfizer

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.
Responsible Party:
Pfizer
ClinicalTrials.gov Identifier:
NCT01564784
Other Study ID Numbers:
  • B1931022
  • 2011-005491-41
First Posted:
Mar 28, 2012
Last Update Posted:
Jan 9, 2019
Last Verified:
Dec 1, 2018
Individual Participant Data (IPD) Sharing Statement:
Yes
Plan to Share IPD:
Yes
Additional relevant MeSH terms:
Leukemia
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Leukemia, Lymphoid
Cytarabine
Fludarabine
Mitoxantrone
Inotuzumab Ozogamicin

Study Results

Participant Flow

Recruitment Details
Pre-assignment Detail 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 164 143
COMPLETED 30 10
NOT COMPLETED 134 133

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 Participants 164 143 307
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]
45.9
(17.07)
45.6
(16.32)
45.7
(16.70)
Sex: Female, Male (Count of 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.
Measure Participants 109 109
Number (95% Confidence Interval) [Percentage of Participants]
80.7
49.2%
29.4
20.6%
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Inotuzumab Ozogamicin, Defined Investigator's Choice of Chemotherapy
Comments
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value <0.0001
Comments
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
Parameter Dispersion Type:
Value:
Estimation Comments
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.
Measure Participants 164 162
Median (95% Confidence Interval) [Months]
7.7
6.2
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Inotuzumab Ozogamicin, Defined Investigator's Choice of Chemotherapy
Comments
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.0105
Comments
Method 1-sided stratified log-rank p-value
Comments
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.751
Confidence Interval (2-Sided) 97.5%
0.568 to 0.993
Parameter Dispersion Type:
Value:
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.
Measure Participants 85 32
Median (95% Confidence Interval) [Months]
5.4
3.5
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Inotuzumab Ozogamicin, Defined Investigator's Choice of Chemotherapy
Comments
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.0021
Comments
Method 1-sided stratified log-rank p-value
Comments
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.490
Confidence Interval (2-Sided) 95%
0.297 to 0.809
Parameter Dispersion Type:
Value:
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.
Measure Participants 164 162
Median (95% Confidence Interval) [Months]
5.0
1.7
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Inotuzumab Ozogamicin, Defined Investigator's Choice of Chemotherapy
Comments
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value <0.0001
Comments
Method 1-sided stratified log-rank p-value
Comments
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.450
Confidence Interval (2-Sided) 97.5%
0.336 to 0.602
Parameter Dispersion Type:
Value:
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.
Measure Participants 164 162
Number (95% Confidence Interval) [Percentage of Participants]
42.7
26%
11.1
7.8%
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Inotuzumab Ozogamicin, Defined Investigator's Choice of Chemotherapy
Comments
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value <0.0001
Comments
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
Parameter Dispersion Type:
Value:
Estimation Comments
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.
Measure Participants 88 32
Number (95% Confidence Interval) [Percentage of Participants]
78.4
47.8%
28.1
19.7%
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Inotuzumab Ozogamicin, Defined Investigator's Choice of Chemotherapy
Comments
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value <0.0001
Comments
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.
Measure Participants 54 22
Number (95% Confidence Interval) [Percentage of Participants]
3.7
2.3%
18.2
12.7%
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
Statistical Test of Hypothesis p-Value 0.3168
Comments
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
Statistical Test of Hypothesis p-Value 0.2160
Comments
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).
Measure Participants 163
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.
Measure Participants 164 162
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
(NA)
Physical Functioning C5D1
11.52
(3.51)
NA
(NA)
Physical Functioning C6D1
7.22
(5.94)
NA
(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
(NA)
Role Functioning C5D1
12.88
(6.10)
NA
(NA)
Role Functioning C6D1
16.67
(11.42)
NA
(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
(NA)
Emotional Functioning C5D1
6.82
(2.83)
NA
(NA)
Emotional Functioning C6D1
2.78
(4.27)
NA
(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
(NA)
Cognitive Functioning C5D1
0.76
(4.17)
NA
(NA)
Cognitive Functioning C6D1
-8.33
(2.51)
NA
(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
(NA)
Social Functioning C5D1
12.88
(6.00)
NA
(NA)
Social Functioning C6D1
16.67
(5.03)
NA
(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
(NA)
Global Health Status C5D1
8.71
(6.68)
NA
(NA)
Global Health Status C6D1
0.69
(6.76)
NA
(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
(NA)
Dyspnoea C5D1
-3.03
(6.55)
NA
(NA)
Dyspnoea C6D1
-2.78
(6.43)
NA
(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
(NA)
Insomnia C5D1
-4.55
(4.55)
NA
(NA)
Insomnia C6D1
-11.11
(9.48)
NA
(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
(NA)
Appetite Loss C5D1
-6.06
(7.80)
NA
(NA)
Appetite Loss C6D1
2.78
(9.59)
NA
(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
(NA)
Constipation C5D1
0.00
(5.37)
NA
(NA)
Constipation C6D1
5.56
(5.56)
NA
(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
(NA)
Diarrhoea C5D1
-9.52
(4.68)
NA
(NA)
Diarrhoea C6D1
-2.78
(4.95)
NA
(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
(NA)
Financial Difficulties C5D1
-3.03
(3.74)
NA
(NA)
Financial Difficulties C6D1
-5.56
(3.75)
NA
(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
(NA)
Fatigue C5D1
-7.32
(5.61)
NA
(NA)
Fatigue C6D1
0.00
(6.42)
NA
(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
(NA)
Nausea and Vomiting C5D1
2.27
(2.96)
NA
(NA)
Nausea and Vomiting C6D1
0.00
(2.90)
NA
(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
(NA)
Pain C5D1
0.76
(7.48)
NA
(NA)
Pain C6D1
-2.78
(9.59)
NA
(NA)
Pain EoT
-1.98
(2.88)
-7.26
(3.75)
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
Statistical Test of Hypothesis p-Value 0.0139
Comments
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
Parameter Dispersion Type:
Value:
Estimation Comments
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
Statistical Test of Hypothesis p-Value 0.0065
Comments
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
Parameter Dispersion Type:
Value:
Estimation Comments
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
Statistical Test of Hypothesis p-Value 0.3307
Comments
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
Parameter Dispersion Type:
Value:
Estimation Comments
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
Statistical Test of Hypothesis p-Value 0.1904
Comments
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
Parameter Dispersion Type:
Value:
Estimation Comments
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
Statistical Test of Hypothesis p-Value 0.0336
Comments
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
Parameter Dispersion Type:
Value:
Estimation Comments
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
Statistical Test of Hypothesis p-Value 0.1572
Comments
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
Parameter Dispersion Type:
Value:
Estimation Comments
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
Statistical Test of Hypothesis p-Value 0.1281
Comments
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
Parameter Dispersion Type:
Value:
Estimation Comments
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
Statistical Test of Hypothesis p-Value 0.6207
Comments
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
Parameter Dispersion Type:
Value:
Estimation Comments
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
Statistical Test of Hypothesis p-Value 0.0193
Comments
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
Parameter Dispersion Type:
Value:
Estimation Comments
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
Statistical Test of Hypothesis p-Value 0.6249
Comments
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
Parameter Dispersion Type:
Value:
Estimation Comments
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
Statistical Test of Hypothesis p-Value 0.1534
Comments
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
Parameter Dispersion Type:
Value:
Estimation Comments
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
Statistical Test of Hypothesis p-Value 0.4915
Comments
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
Parameter Dispersion Type:
Value:
Estimation Comments
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
Statistical Test of Hypothesis p-Value 0.1789
Comments
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
Parameter Dispersion Type:
Value:
Estimation Comments
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
Statistical Test of Hypothesis p-Value 0.4578
Comments
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
Parameter Dispersion Type:
Value:
Estimation Comments
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
Statistical Test of Hypothesis p-Value 0.8428
Comments
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
Parameter Dispersion Type:
Value:
Estimation Comments
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.
Measure Participants 164 162
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
(NA)
Cycle 5, Day 1
0.04
(0.04)
NA
(NA)
Cycle 6, Day 1
0.03
(0.04)
NA
(NA)
EoT
-0.01
(0.02)
-0.04
(0.02)
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Inotuzumab Ozogamicin, Defined Investigator's Choice of Chemotherapy
Comments
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.1710
Comments
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
Parameter Dispersion Type:
Value:
Estimation Comments
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.
Measure Participants 164 162
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
(NA)
Cycle 5, Day 1
7.62
(4.43)
NA
(NA)
Cycle 6, Day 1
15.09
(9.14)
NA
(NA)
EoT
4.62
(2.38)
-0.52
(2.88)
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Inotuzumab Ozogamicin, Defined Investigator's Choice of Chemotherapy
Comments
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.1172
Comments
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
Parameter Dispersion Type:
Value:
Estimation Comments
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.
Measure Participants 79 35
Number [Percentage of Participants]
22.8
13.9%
8.6
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 (%) # Events Affected / at Risk (%) # Events
Total / (NaN) / (NaN)
Serious Adverse Events
Inotuzumab Ozogamicin Defined Investigator's Choice of Chemotherapy
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total 85/164 (51.8%) 72/143 (50.3%)
Blood and lymphatic system disorders
Anaemia 1/164 (0.6%) 0/143 (0%)
Febrile neutropenia 19/164 (11.6%) 27/143 (18.9%)
Leukopenia 1/164 (0.6%) 0/143 (0%)
Neutropenia 2/164 (1.2%) 0/143 (0%)
Pancytopenia 0/164 (0%) 2/143 (1.4%)
Thrombocytopenia 1/164 (0.6%) 1/143 (0.7%)
Cardiac disorders
Acute coronary syndrome 1/164 (0.6%) 0/143 (0%)
Atrial fibrillation 1/164 (0.6%) 1/143 (0.7%)
Cardiac arrest 1/164 (0.6%) 0/143 (0%)
Cardiac failure congestive 1/164 (0.6%) 0/143 (0%)
Left ventricular dysfunction 2/164 (1.2%) 0/143 (0%)
Myocardial infarction 1/164 (0.6%) 0/143 (0%)
Pericarditis 1/164 (0.6%) 0/143 (0%)
Eye disorders
Blindness unilateral 1/164 (0.6%) 0/143 (0%)
Gastrointestinal disorders
Abdominal pain 3/164 (1.8%) 1/143 (0.7%)
Abdominal pain lower 1/164 (0.6%) 0/143 (0%)
Abdominal pain upper 1/164 (0.6%) 0/143 (0%)
Ascites 1/164 (0.6%) 0/143 (0%)
Colitis ischaemic 1/164 (0.6%) 0/143 (0%)
Diarrhoea 0/164 (0%) 1/143 (0.7%)
Dysphagia 0/164 (0%) 1/143 (0.7%)
Gastritis haemorrhagic 1/164 (0.6%) 0/143 (0%)
Gastrointestinal haemorrhage 1/164 (0.6%) 0/143 (0%)
Ileal perforation 0/164 (0%) 1/143 (0.7%)
Intestinal ischaemia 1/164 (0.6%) 1/143 (0.7%)
Intra-abdominal haemorrhage 1/164 (0.6%) 0/143 (0%)
Large intestinal ulcer 1/164 (0.6%) 0/143 (0%)
Lower gastrointestinal haemorrhage 1/164 (0.6%) 0/143 (0%)
Mesenteric haemorrhage 1/164 (0.6%) 0/143 (0%)
Nausea 2/164 (1.2%) 0/143 (0%)
Oesophageal stenosis 0/164 (0%) 1/143 (0.7%)
Pancreatitis 1/164 (0.6%) 0/143 (0%)
Proctalgia 0/164 (0%) 1/143 (0.7%)
Small intestinal obstruction 1/164 (0.6%) 0/143 (0%)
Stomatitis 2/164 (1.2%) 1/143 (0.7%)
Upper gastrointestinal haemorrhage 1/164 (0.6%) 0/143 (0%)
Vomiting 1/164 (0.6%) 0/143 (0%)
General disorders
Asthenia 3/164 (1.8%) 0/143 (0%)
Chest pain 1/164 (0.6%) 0/143 (0%)
Disease progression 8/164 (4.9%) 5/143 (3.5%)
Fatigue 1/164 (0.6%) 0/143 (0%)
Mucosal inflammation 0/164 (0%) 1/143 (0.7%)
Multiple organ dysfunction syndrome 2/164 (1.2%) 2/143 (1.4%)
Pain 1/164 (0.6%) 0/143 (0%)
Pyrexia 5/164 (3%) 3/143 (2.1%)
Hepatobiliary disorders
Cholecystitis 1/164 (0.6%) 0/143 (0%)
Hepatic vein thrombosis 1/164 (0.6%) 0/143 (0%)
Hyperbilirubinaemia 0/164 (0%) 3/143 (2.1%)
Venoocclusive liver disease 23/164 (14%) 3/143 (2.1%)
Infections and infestations
Adenoviral upper respiratory infection 1/164 (0.6%) 0/143 (0%)
Appendicitis 0/164 (0%) 1/143 (0.7%)
Bacteraemia 3/164 (1.8%) 1/143 (0.7%)
Bacterial infection 0/164 (0%) 1/143 (0.7%)
Brain abscess 1/164 (0.6%) 0/143 (0%)
Bronchopulmonary aspergillosis 0/164 (0%) 1/143 (0.7%)
Candida infection 1/164 (0.6%) 1/143 (0.7%)
Cellulitis 1/164 (0.6%) 1/143 (0.7%)
Clostridium difficile colitis 2/164 (1.2%) 1/143 (0.7%)
Clostridium difficile infection 1/164 (0.6%) 0/143 (0%)
Corona virus infection 1/164 (0.6%) 0/143 (0%)
Cytomegalovirus chorioretinitis 0/164 (0%) 1/143 (0.7%)
Device related infection 1/164 (0.6%) 0/143 (0%)
Diverticulitis 1/164 (0.6%) 0/143 (0%)
Enteritis necroticans 0/164 (0%) 1/143 (0.7%)
Enterococcal bacteraemia 1/164 (0.6%) 0/143 (0%)
Enterococcal sepsis 1/164 (0.6%) 0/143 (0%)
Escherichia bacteraemia 2/164 (1.2%) 2/143 (1.4%)
Escherichia sepsis 1/164 (0.6%) 2/143 (1.4%)
Febrile infection 1/164 (0.6%) 0/143 (0%)
Fungaemia 1/164 (0.6%) 0/143 (0%)
Fungal infection 1/164 (0.6%) 0/143 (0%)
Herpes zoster 1/164 (0.6%) 0/143 (0%)
Infection 1/164 (0.6%) 0/143 (0%)
Influenza 2/164 (1.2%) 0/143 (0%)
Klebsiella bacteraemia 0/164 (0%) 1/143 (0.7%)
Klebsiella infection 0/164 (0%) 1/143 (0.7%)
Liver abscess 0/164 (0%) 1/143 (0.7%)
Lung infection 1/164 (0.6%) 2/143 (1.4%)
Necrotising fasciitis fungal 0/164 (0%) 1/143 (0.7%)
Neutropenic sepsis 3/164 (1.8%) 4/143 (2.8%)
Parainfluenzae virus infection 1/164 (0.6%) 0/143 (0%)
Pneumonia 10/164 (6.1%) 0/143 (0%)
Pneumonia fungal 0/164 (0%) 3/143 (2.1%)
Pneumonia pseudomonal 0/164 (0%) 1/143 (0.7%)
Pseudomonal bacteraemia 1/164 (0.6%) 2/143 (1.4%)
Pseudomonal sepsis 1/164 (0.6%) 0/143 (0%)
Respiratory tract infection 1/164 (0.6%) 0/143 (0%)
Sepsis 4/164 (2.4%) 10/143 (7%)
Septic embolus 1/164 (0.6%) 0/143 (0%)
Septic shock 3/164 (1.8%) 3/143 (2.1%)
Serratia bacteraemia 1/164 (0.6%) 0/143 (0%)
Sinusitis fungal 1/164 (0.6%) 0/143 (0%)
Staphylococcal bacteraemia 1/164 (0.6%) 1/143 (0.7%)
Staphylococcal sepsis 2/164 (1.2%) 1/143 (0.7%)
Systemic candida 1/164 (0.6%) 1/143 (0.7%)
Systemic mycosis 0/164 (0%) 1/143 (0.7%)
Urinary tract infection 1/164 (0.6%) 1/143 (0.7%)
Urinary tract infection fungal 1/164 (0.6%) 0/143 (0%)
Mucormycosis 1/164 (0.6%) 0/143 (0%)
Injury, poisoning and procedural complications
Fall 1/164 (0.6%) 0/143 (0%)
Subdural haematoma 1/164 (0.6%) 3/143 (2.1%)
Metabolism and nutrition disorders
Fluid overload 1/164 (0.6%) 0/143 (0%)
Hyperglycaemia 2/164 (1.2%) 0/143 (0%)
Lactic acidosis 1/164 (0.6%) 0/143 (0%)
Tumour lysis syndrome 2/164 (1.2%) 0/143 (0%)
Musculoskeletal and connective tissue disorders
Arthralgia 1/164 (0.6%) 0/143 (0%)
Back pain 2/164 (1.2%) 0/143 (0%)
Bone infarction 1/164 (0.6%) 0/143 (0%)
Neck pain 1/164 (0.6%) 0/143 (0%)
Osteonecrosis 1/164 (0.6%) 0/143 (0%)
Nervous system disorders
Cerebrovascular accident 0/164 (0%) 1/143 (0.7%)
Haemorrhage intracranial 1/164 (0.6%) 1/143 (0.7%)
Headache 2/164 (1.2%) 0/143 (0%)
Nervous system disorder 1/164 (0.6%) 1/143 (0.7%)
Renal and urinary disorders
Acute kidney injury 2/164 (1.2%) 0/143 (0%)
Haematuria 1/164 (0.6%) 0/143 (0%)
Respiratory, thoracic and mediastinal disorders
Acute respiratory distress syndrome 1/164 (0.6%) 0/143 (0%)
Epistaxis 0/164 (0%) 1/143 (0.7%)
Pharyngeal stenosis 0/164 (0%) 1/143 (0.7%)
Pleural effusion 1/164 (0.6%) 0/143 (0%)
Respiratory failure 2/164 (1.2%) 6/143 (4.2%)
Respiratory tract oedema 0/164 (0%) 1/143 (0.7%)
Skin and subcutaneous tissue disorders
Dermatitis allergic 1/164 (0.6%) 0/143 (0%)
Vascular disorders
Hypertension 0/164 (0%) 1/143 (0.7%)
Hypotension 0/164 (0%) 3/143 (2.1%)
Shock haemorrhagic 1/164 (0.6%) 0/143 (0%)
Thrombophlebitis 0/164 (0%) 1/143 (0.7%)
Other (Not Including Serious) Adverse Events
Inotuzumab Ozogamicin Defined Investigator's Choice of Chemotherapy
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total 159/164 (97%) 143/143 (100%)
Blood and lymphatic system disorders
Anaemia 54/164 (32.9%) 79/143 (55.2%)
Febrile neutropenia 27/164 (16.5%) 52/143 (36.4%)
Leukopenia 47/164 (28.7%) 54/143 (37.8%)
Lymphopenia 31/164 (18.9%) 36/143 (25.2%)
Neutropenia 79/164 (48.2%) 66/143 (46.2%)
Thrombocytopenia 80/164 (48.8%) 86/143 (60.1%)
Cardiac disorders
Tachycardia 6/164 (3.7%) 16/143 (11.2%)
Eye disorders
Dry eye 1/164 (0.6%) 8/143 (5.6%)
Gastrointestinal disorders
Abdominal distension 10/164 (6.1%) 2/143 (1.4%)
Abdominal pain 19/164 (11.6%) 26/143 (18.2%)
Abdominal pain upper 11/164 (6.7%) 12/143 (8.4%)
Constipation 28/164 (17.1%) 34/143 (23.8%)
Diarrhoea 30/164 (18.3%) 55/143 (38.5%)
Dyspepsia 3/164 (1.8%) 9/143 (6.3%)
Nausea 52/164 (31.7%) 68/143 (47.6%)
Stomatitis 5/164 (3%) 9/143 (6.3%)
Vomiting 25/164 (15.2%) 35/143 (24.5%)
General disorders
Asthenia 14/164 (8.5%) 14/143 (9.8%)
Chest pain 3/164 (1.8%) 9/143 (6.3%)
Chills 18/164 (11%) 17/143 (11.9%)
Fatigue 41/164 (25%) 24/143 (16.8%)
Mucosal inflammation 6/164 (3.7%) 19/143 (13.3%)
Oedema peripheral 13/164 (7.9%) 13/143 (9.1%)
Pain 12/164 (7.3%) 8/143 (5.6%)
Pyrexia 49/164 (29.9%) 57/143 (39.9%)
Hepatobiliary disorders
Hyperbilirubinaemia 35/164 (21.3%) 23/143 (16.1%)
Infections and infestations
Bacteraemia 4/164 (2.4%) 13/143 (9.1%)
Pneumonia 4/164 (2.4%) 12/143 (8.4%)
Sinusitis 4/164 (2.4%) 8/143 (5.6%)
Injury, poisoning and procedural complications
Contusion 10/164 (6.1%) 3/143 (2.1%)
Fall 11/164 (6.7%) 4/143 (2.8%)
Investigations
Alanine aminotransferase increased 25/164 (15.2%) 18/143 (12.6%)
Aspartate aminotransferase increased 37/164 (22.6%) 16/143 (11.2%)
Blood alkaline phosphatase increased 21/164 (12.8%) 10/143 (7%)
Gamma-glutamyltransferase increased 35/164 (21.3%) 12/143 (8.4%)
Lipase increased 15/164 (9.1%) 1/143 (0.7%)
White blood cell count decreased 10/164 (6.1%) 9/143 (6.3%)
Metabolism and nutrition disorders
Decreased appetite 19/164 (11.6%) 18/143 (12.6%)
Fluid overload 2/164 (1.2%) 8/143 (5.6%)
Hyperglycaemia 11/164 (6.7%) 12/143 (8.4%)
Hypoalbuminaemia 10/164 (6.1%) 7/143 (4.9%)
Hypocalcaemia 11/164 (6.7%) 15/143 (10.5%)
Hypokalaemia 25/164 (15.2%) 33/143 (23.1%)
Hypomagnesaemia 10/164 (6.1%) 12/143 (8.4%)
Hyponatraemia 5/164 (3%) 9/143 (6.3%)
Hypophosphataemia 9/164 (5.5%) 10/143 (7%)
Musculoskeletal and connective tissue disorders
Arthralgia 9/164 (5.5%) 7/143 (4.9%)
Back pain 16/164 (9.8%) 10/143 (7%)
Bone pain 3/164 (1.8%) 10/143 (7%)
Pain in extremity 13/164 (7.9%) 16/143 (11.2%)
Nervous system disorders
Dizziness 12/164 (7.3%) 16/143 (11.2%)
Headache 45/164 (27.4%) 38/143 (26.6%)
Psychiatric disorders
Anxiety 8/164 (4.9%) 11/143 (7.7%)
Depression 4/164 (2.4%) 9/143 (6.3%)
Insomnia 24/164 (14.6%) 22/143 (15.4%)
Respiratory, thoracic and mediastinal disorders
Cough 22/164 (13.4%) 23/143 (16.1%)
Dyspnoea 10/164 (6.1%) 18/143 (12.6%)
Epistaxis 24/164 (14.6%) 12/143 (8.4%)
Oropharyngeal pain 6/164 (3.7%) 10/143 (7%)
Pleural effusion 3/164 (1.8%) 8/143 (5.6%)
Skin and subcutaneous tissue disorders
Erythema 7/164 (4.3%) 9/143 (6.3%)
Pruritus 8/164 (4.9%) 10/143 (7%)
Rash 14/164 (8.5%) 27/143 (18.9%)
Vascular disorders
Hypertension 9/164 (5.5%) 8/143 (5.6%)
Hypotension 12/164 (7.3%) 22/143 (15.4%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

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
Responsible Party:
Pfizer
ClinicalTrials.gov Identifier:
NCT01564784
Other Study ID Numbers:
  • B1931022
  • 2011-005491-41
First Posted:
Mar 28, 2012
Last Update Posted:
Jan 9, 2019
Last Verified:
Dec 1, 2018