AzTrials
AzTrials

Acute Lymphoblastic LeukemiaPhase 3NCT01564784

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

A Phase 3 study testing inotuzumab ozogamicin, FLAG (fludarabine, cytarabine and G-CSF) and HIDAC (high dose cytarabine) in people with Acute Lymphoblastic Leukemia, run by Pfizer at 198 sites in 20 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Acute Lymphoblastic Leukemia
What is being tested?
inotuzumab ozogamicin, FLAG (fludarabine, cytarabine and G-CSF) and HIDAC (high dose cytarabine)
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
326 participants
Where
198 sitesin 20 countries
Study dates
2 Aug 2012to 4 Jan 2017
Phase
Phase 3
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • CD22 expression
  • Adequate liver and renal functions

Who cannot join

  • Isolated extramedullary disease
  • Active Central Nervous System [CNS] disease

Trial locations and contacts

198 sites in 20 countries.

198 sites in 20 countries

United States96 sites

  • University of New Mexico Comprehensive Cancer Center

    Albuquerque, New Mexico, 87131-0001

  • UNM Cancer Center

    Albuquerque, New Mexico, 87131

  • University of Michigan Health System-

    Ann Arbor, Michigan, 48109

  • Emory University Hospital

    Atlanta, Georgia, 30322

  • Investigational Drug Service, Emory University Clinic

    Atlanta, Georgia, 30322

  • The Emory Clinic

    Atlanta, Georgia, 30322

  • Winship Cancer Institute, Emory University

    Atlanta, Georgia, 30322

  • Blood and Marrow Transplant Group of Georgia

    Atlanta, Georgia, 30342

  • Northside Hospital

    Atlanta, Georgia, 30342

  • Georgia Regents Medical Center Pharmacy, Georgia Regents University Cancer Center

    Augusta, Georgia, 30912

  • Georgia Regents University

    Augusta, Georgia, 30912

  • University of Colorado Cancer Center

    Aurora, Colorado, 80045

  • University of Colorado Hospital, Cancer Center Infusion Center

    Aurora, Colorado, 80045

  • University of Colorado Hospital

    Aurora, Colorado, 80045

  • University of Maryland

    Baltimore, Maryland, 21201

  • Oncology Investigational Drug Service

    Baltimore, Maryland, 21231-2410

  • The Sidney Kimmel Comprehensive Cancer Center

    Baltimore, Maryland, 21231-2410

  • Massachusetts General Hospital (MGH)

    Boston, Massachusetts, 02114

  • Brigham and Women's Hospital

    Boston, Massachusetts, 02115

  • Dana-Farber Cancer Institute

    Boston, Massachusetts, 02215

  • UNC Cancer Hospital Infusion Pharmacy

    Chapel Hill, North Carolina, 27514

  • UNC Hospitals - The University of North Carolina at Chapel Hill

    Chapel Hill, North Carolina, 27599-7600

  • Hollings Cancer Center

    Charleston, South Carolina, 29425

  • MUSC Hospital

    Charleston, South Carolina, 29425

  • Northwestern Medical Faculty Foundation

    Chicago, Illinois, 60611

  • Northwestern Medicine Developmental Therapeutics Institute

    Chicago, Illinois, 60611

  • Northwestern Memorial Hospital

    Chicago, Illinois, 60611

  • The University of Chicago

    Chicago, Illinois, 60637

  • University of Chicago Medical Center, Dept. of Pharmacy

    Chicago, Illinois, 60637

  • University of Cincinnati Medical Center

    Cincinnati, Ohio, 45219

  • University Hospitals of Cleveland

    Cleveland, Ohio, 44106

  • Cleveland Clinic Foundation

    Cleveland, Ohio, 44195

  • Parkland Health and Hospital System

    Dallas, Texas, 75235

  • Baylor Charles A. Sammons Cancer Center

    Dallas, Texas, 75246

  • Baylor University Medical Center

    Dallas, Texas, 75246

  • University of Texas Southwestern Universtiy Hospital - William P Clements Jr.

    Dallas, Texas, 75390

  • UT Southwestern Medical Center at Dallas

    Dallas, Texas, 75390

  • UT Southwestern University Hospital- Zale Lipshy

    Dallas, Texas, 75390

  • Karmanos Cancer Institute

    Detroit, Michigan, 48201

  • Karmanos Cancer Institute Weisberg Cancer Treatment Center

    Farmington Hills, Michigan, 48334

  • Hackensack University Medical Center

    Hackensack, New Jersey, 07601

  • John Theurer Cancer Center at Hackensack University Medical Center

    Hackensack, New Jersey, 07601

  • IDS-investigational drug pharmacy Penn State Milton S. Hershey Medical Center

    Hershey, Pennsylvania, 17033

  • Penn State Milton S. Hershey Medical Center,

    Hershey, Pennsylvania, 17033

  • The University of Texas MD Anderson Cancer Center

    Houston, Texas, 77030

  • University of Iowa Hospitals and Clinics

    Iowa City, Iowa, 52242

  • University of Kansas Hospital

    Kansas City, Kansas, 66160

  • Investigational Drug Services - UC San Diego Moores Cancer Center

    La Jolla, California, 92037-0845

  • UC San Diego Medical Center - La Jolla

    La Jolla, California, 92037

  • UC San Diego Moores Cancer Center

    La Jolla, California, 92093-0698

  • Monter Cancer Center

    Lake Success, New York, 11042

  • Children's Center for Cancer and Blood Diseases, Childrens Hospital Los Angeles

    Los Angeles, California, 90027

  • Keck Hospital of USC

    Los Angeles, California, 90033

  • LAC+USC Medical Center

    Los Angeles, California, 90033

  • USC Norris Comprehensive Cancer Center

    Los Angeles, California, 90033

  • USC/Norris Comprehensive Cancer Center / Investigational Drug Services

    Los Angeles, California, 90033

  • USC/Norris Comprehensive Cancer Center

    Los Angeles, California, 90033

  • UCLA Drug Information/Investigation Drug

    Los Angeles, California, 90095

  • UCLA Hematology/Oncology Clinic

    Los Angeles, California, 90095

  • UCLA Ronald Reagan Medical Center

    Los Angeles, California, 90095

  • UCLA Rrmc

    Los Angeles, California, 90095

  • Norton Cancer Institute

    Louisville, Kentucky, 40202

  • Norton Cancer Institute, Suburban

    Louisville, Kentucky, 40207

  • North Shore University Hospital

    Manhasset, New York, 11030

  • Miami Children's Hospital

    Miami, Florida, 33155

  • West Virginia University Hospitals Pharmaceutical Services

    Morgantown, West Virginia, 26506

  • West Virginia University Hospitals

    Morgantown, West Virginia, 26506

  • Rutgers Cancer Institute of New Jersey

    New Brunswick, New Jersey, 08903

  • Yale-New Haven Hospital & Smilow Cancer Center

    New Haven, Connecticut, 06510

  • New York Presbyterian Hospital-Weill Cornell Medical College

    New York, New York, 10021

  • NewYork-Presbyterian Hospital

    New York, New York, 10065

  • Weill Cornell Medical College - New York-Presbyterian Hospital

    New York, New York, 10065

  • OU Medical Center Presbyterian Tower

    Oklahoma City, Oklahoma, 73104

  • Stephenson Cancer Center

    Oklahoma City, Oklahoma, 73104

  • UC Irvine Medical Center

    Orange, California, 92868-3201

  • Children's Hospital of Orange County

    Orange, California, 92868

  • UC Irvine Medical Center

    Orange, California, 92868

  • MD Anderson Cancer Center Orlando - 5th Floor Investigational Pharmacy

    Orlando, Florida, 32806

  • MD Anderson Cancer Center Orlando

    Orlando, Florida, 32806

  • Orlando Heart Health Institute

    Orlando, Florida, 32806

  • Orlando Regional Medical Center

    Orlando, Florida, 32806

  • Freidenrich Center for Translational Research (CTRU), Stanford University

    Palo Alto, California, 94304

  • University of Rochester Medical Center

    Rochester, New York, 14642

  • LDS Hospital

    Salt Lake City, Utah, 84143

  • UC San Diego Medical Center - Hillcrest

    San Diego, California, 92103

  • Seattle Cancer Care Alliance

    Seattle, Washington, 98109

  • University of Washington

    Seattle, Washington, 98195

  • Martha Hamilton, Investigational Drug Services, Dept of Pharmacy

    Stanford, California, 94305

  • Stanford Cancer Institute

    Stanford, California, 94305

  • Stanford University Hospital and Clinics

    Stanford, California, 94305

  • Stony Brook University Medical Center

    Stony Brook, New York, 11794-7007

  • Stony Brook University Medical Center, The Cancer Center

    Stony Brook, New York, 11794-9447

  • Division of Hematology/Oncology, Stony Brook University Hospital

    Stony Brook, New York, 11794

  • Stony Brook University Medical Center

    Stony Brook, New York, 11794

  • University of Kansas Cancer Center

    Westwood, Kansas, 66205

  • Wake Forest Baptist Health

    Winston-Salem, North Carolina, 27157

Other trials in United States

Italy26 sites

  • Istituto di Ematologia Seragnoli

    Bologna, 40138

  • Azienda Ospedaliera Brotzu CTMO P.O. Businco

    Cagliari, CA, 09121

  • Farmacia

    Cagliari, CA, 09121

  • U.O. Radiodiagnostica

    Cagliari, CA, 09121

  • A.O.U. Vittorio Emanuele di Catania-Ospedale Ferrarotto

    Catania, 95124

  • Radiology (Radiology Only)

    Catania, 95124

  • U.O. di Ematologia Dip. Medicine Specialistiche A.O.U. Arcispedale Sant'Anna

    Cona, Ferrara, 44124

  • Clinica Ematologica

    Genova, 16132

  • Pharmacy

    Genova, 16132

  • Radiology Department (Radiology ONLY)

    Genova, 16132

  • Radiology Department

    Genova, 16132

  • U.O. Ematologia 1

    Genova, 16132

  • IRST-Ematologia

    Meldola (FC), FC, 47014

  • S.C. Pharmacy

    Milan, 20162

  • S.C. Radiology

    Milan, 20162

  • SC Ematologia

    Milan, 20162

  • A.O. San Gerardo - Farmacia

    Monza, 20900

  • A.O. San Gerardo di Monza

    Monza, 20900

  • AORN "A. Cardarelli"

    Naples, 80131

  • RAdiology Department (RAdiology only)

    Naples, 80131

  • Clinica Ematologica

    Pavia, 27100

  • Radiologist Department

    Ravenna, 48121

  • Servizio di Farmacia

    Ravenna, 48121

  • U.O. Ematologia, Ospedale S. Maria delle Croci

    Ravenna, 48121

  • Clinica Ematologica

    Udine, 33100

  • Radiology (Radiology Only)

    Udine, 33100

Other trials in Italy

Spain11 sites

  • Hospital Universitari Germans Trias i Pujol

    Badalona, Barcelona, 08916

  • Hospital Vall d'Hebron

    Barcelona, Catalonia, 08035

  • Hospital de la Santa Creu i Sant Pau(Nuevo Hospital)

    Barcelona, 08025

  • Hospital General Universitario Gregorio Maranon

    Madrid, 28007

  • Hospital Ramon y Cajal

    Madrid, 28034

  • Hospital Universitario 12 de Octubre

    Madrid, 28041

  • Hospital General Universitario Jose Maria Morales Meseguer

    Murcia, 30008

  • Hospital Son Llatzer

    Palma de Mallorca, Mallorca, 07198

  • Hospital Universitario de Salamanca

    Salamanca, Castille and LION, 37007

  • Hospital Universitario Virgen del Rocio

    Seville, 41013

  • Hospital Clinico Universitario de Valencia

    Valencia, 46010

Other trials in Spain

France10 sites

  • CHU de Dijon-Hopital d'Enfants-Service d'hematologie Clinique

    Dijon, 21000

  • C.H.U. de Grenoble, Hopital Albert Michallon

    Grenoble, 38043

  • Hopital Universitaire Andre Mignot

    Le Chesnay, 78157

  • CHU Dupuytren

    Limoges, 87042

  • Institut Paoli-Calmettes

    Marseille, 13009

  • Hôpital Saint-Louis

    Paris, 75475

  • Centre Hospitalier Lyon Sud

    Pierre-Bénite, 69495

  • Institut de Cancérologie Lucien Neuwirth

    Saint-Priest-en-Jarez, 42271

  • Iuct - Oncopole

    Toulouse, 31059

  • CHU Brabois- Service d'hematologie

    Vandœuvre-lès-Nancy, 54511

Other trials in France

Japan8 sites

  • Akita University Hospital

    Akita, 010-8543

  • National Cancer Center Hospital

    Chuo-ku, Tokyo, 1040045

  • National Hospital Organization Kyushu Cancer Center

    Fukuoka, 8111395

  • Tokai University Hospital

    Kanagawa, 259-1193

  • Nagoya Daini Red Cross Hospital

    Nagoya, Aichi-ken, 4668650

  • The Hospital of Hyogo College of Medicine

    Nishinomiya-shi, Hyōgo, 6638501

  • Osaka City University Hospital

    Osaka, Osaka, 5458586

  • Tohoku University Hospital

    Sendai, Miyagi, 9808574

Other trials in Japan

China7 sites

  • Beijing Chao-yang Hospital

    Beijing, 100020

  • Peking University People's Hospital

    Beijing, 100044

  • The 307th Hospital of PLA

    Beijing, 100071

  • The first hospital of jilin university

    Changchun, Jilin, 130021

  • Guangdong General Hospital

    Guangzhou, Guangdong, 510080

  • Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences,

    Tianjin, 300020

  • Henan Cancer Hostipal

    Zhengzhou, Henan, 450008

Other trials in China

Germany7 sites

  • Universitätsklinikum Köln, Klinik I für Innere Medizin

    Cologne, 50937

  • Klinikum der Goethe Universitaet

    Frankfurt, 60590

  • Universitaetsklinikum Heidelberg

    Heidelberg, 69120

  • Klinikum Rechts der Isar der TU München

    München, 81675

  • Zentralapotheke des Universitaetsklinikums Muenster

    Münster, North Rhine-Westphalia, 48149

  • Institut fuer klinische Radiologie

    Münster, 48149

  • Universitaetsklinikum Muenster

    Münster, 48149

Other trials in Germany

United Kingdom7 sites

  • Bristol Haematology and Oncology Centre

    Bristol, BS2 8ED

  • Castle Hill Hospital

    Hull, HU16 5JQ

  • Department of Academic Oncology

    London, NW3 2QG

  • The Christie NHS Foundation Trust

    Manchester, M20 4BX

  • Nottingham University Hospitals NHS Trust

    Nottingham, NG5 1PB

  • Churchill Hospital

    Oxford, OX3 7LJ

  • Southampton General Hospital

    Southampton, Hampshire, SO16 6YD

Other trials in United Kingdom

Poland4 sites

  • Klinika Hematologii i Transplantologii

    Gdansk, 80-952

  • Oddzial Hematologii, Klinika Hematologii, Regionalny Osrodek Onkologiczny Wojewodzki Szpital

    Lodz, 93510

  • Instytut Hematologii i Transfuzjologii, Klinika Hematologii

    Warsaw, 02-776

  • Dolnoslaskie Centrum Transplantacji Komorkowych z Krajowym Bankiem Dawcow Szpiku

    Wroclaw, 53-439

Other trials in Poland

Czechia3 sites

  • Interni Hematologicka a Onkologicka Klinika

    Brno, 62500

  • Fakultni Nemocnice Hradec Kralove

    Hradec Králové, 50005

  • Fakultni nemocnice Kralovske Vinohrady

    Prague, 10034

Other trials in Czechia

South Korea3 sites

  • Chonnam National University, Hwasun Hospital

    Hwasun-Gun, Jeollanam-do, 519-763

  • Asan Medical Center

    Seoul, 05505

  • Samsung Medical Center

    Seoul, 135 710

Other trials in South Korea

Australia2 sites

  • Royal Adelaide Hospital

    Adelaide, South Australia, 5000

  • Eastern Clinical Research Unit, Box Hill Hospital

    Box Hill, Victoria, 3128

Other trials in Australia

Finland2 sites

  • HUS-Kuvantaminen

    Helsinki, 00290

  • HYKS/Hematologian klinikka

    Helsinki, 00290

Other trials in Finland

Hungary2 sites

  • Egyesitett Szent Istvan és Szent Laszlo Korhaz-Rendelointezet;

    Budapest, 1097

  • Debreceni Egyetem Orvos-es Egeszsegtudomanyi Centrum II. Belgyogyaszati Klinika

    Debrecen, 4032

Other trials in Hungary

Netherlands2 sites

  • Erasmus Medical Center

    Rotterdam, South Holland, 3015 CE

  • Erasmus Medical Center

    Rotterdam, South Holland, 3075 EA

Other trials in Netherlands

Singapore2 sites

  • National University Hospital/National University Cancer Institute Singapore (NCIS)

    Singapore, 119228

  • Singapore General Hospital

    Singapore, 169608

Other trials in Singapore

Sweden2 sites

  • Universitetssjukhus Lund, Hematologkliniken

    Lund, 221 85

  • Hematology Center

    Stockholm, 17176

Other trials in Sweden

Taiwan2 sites

  • Chang Gung Medical Foundation, Kaohsiung Branch

    Kaohsiung City, 83301

  • National Taiwan University Hospital

    Taipei, 10002

Other trials in Taiwan

Argentina1 site

  • Sanatorio Allende

    Córdoba, 5000

Other trials in Argentina

Canada1 site

  • Princess Margaret Cancer Centre

    Toronto, Ontario, M5G 2M9

Other trials in Canada

About this study

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)

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

Being tested
inotuzumab ozogamicin, FLAG (fludarabine, cytarabine and G-CSF), HIDAC (high dose cytarabine), cytarabine and mitoxantrone
Medical subject headings
Precursor Cell Lymphoblastic Leukemia-Lymphoma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • inotuzumab ozogamicinDrug

    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)Drug

    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)Drug

    cytarabine 3 g/m^2 IV every 12 hours for up to 12 times

  • cytarabine and mitoxantroneDrug

    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

Study groups in NCT01564784
Study groupRoleWhat they receive
Arm AExperimentalNot described
Receives: Drug: inotuzumab ozogamicin
Arm BActive comparatorNot described
Receives: Drug: FLAG (fludarabine, cytarabine and G-CSF); Drug: HIDAC (high dose cytarabine); Drug: cytarabine and mitoxantrone

What is being measured

The primary outcome is the main question the study is designed to answer.

  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)

    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.

    Measured: 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

  2. 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.

    Measured: Up to 5 years after randomization or 2 years from randomization of the last participant, whichever occurs first.

Secondary outcomes (10)

  1. 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.

    Measured: Up to 2 years from randomization

  2. 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.

    Measured: Up to 2 years from randomization

  3. 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.

    Measured: Up to 19 weeks from last dose

  4. 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.

    Measured: Up to approximately 4 weeks (EoT) from last dose of study drug

  5. 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.

    Measured: Up to approximately 4 weeks (EoT) from last dose of study drug

  6. 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).

    Measured: Days 1, 4, 8, and 15 of Cycle 1, Days 1 and 8 of Cycle 2 and Day 1 of Cycle 4

  7. 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.

    Measured: Day 1 of each cycle prior to dosing and EoT

  8. 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).

    Measured: Day 1 of each cycle prior to dosing and EoT

  9. 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.

    Measured: Day 1 of each cycle prior to dosing and EoT

  10. 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.

    Measured: Up to 2 years from randomization

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted28 Mar 2012 (estimated)
  2. Study start2 Aug 2012
  3. Primary completion8 Mar 2016
  4. Study completion4 Jan 2017

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
326 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01564784
Sponsor's protocol ID
B1931022
Other IDs
2011-005491-41
Status last verified
Dec 2018
First submitted
26 Mar 2012
Last updated
9 Jan 2019
Data monitoring committee
Yes
Individual data sharing
Yes: Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical\_trials/trial\_data\_and\_results/data\_requests.

Publications

  • Zhao Y, Laird AD, Roberts KG, Yafawi R, Kantarjian H, DeAngelo DJ, Stelljes M, Liedtke M, Stock W, Gokbuget N, O'Brien S, Jabbour E, Cassaday RD, Loyd MR, Olsen S, Neale G, Liu X, Vandendries E, Advani A, Mullighan CG. Association of leukemic molecular profile with efficacy of inotuzumab ozogamicin in adults with relapsed/refractory ALL. Blood Adv. 2024 Jun 25;8(12):3226-3236. doi: 10.1182/bloodadvances.2023012430.

    PubMed 38607410

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

    PubMed 35643855

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

    PubMed 35622074

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

    PubMed 33602684

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

    PubMed 33231879

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

    PubMed 32769965

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

    PubMed 31790983

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

    PubMed 31655984

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

    PubMed 30920645

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

    PubMed 29381191

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

    PubMed 29330398

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

    PubMed 28687420

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

    PubMed 27292104

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing inotuzumab ozogamicin, FLAG (fludarabine, cytarabine and G-CSF) and HIDAC (high dose cytarabine) in people with Acute Lymphoblastic Leukemia, run by Pfizer at 198 sites in 20 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 2 inclusion and 2 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 9 Jan 2019. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 198 sites in United States, Italy, Spain, France, Japan and 15 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 17 Jan 2018). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Percentage of Participants With Hematologic Remission (Complete Remission [CR]/Complete Remission With Incomplete Hematologic Recovery [CRi]) as Assessed by the Endpoint Adjudication Committee (EAC) (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). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01564784, which also lists 13 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Jan 2019.

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