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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT01564784




Registration number
NCT01564784
Ethics application status
Date submitted
26/03/2012
Date registered
28/03/2012
Date last updated
9/01/2019

Titles & IDs
Public title
A Study Of Inotuzumab Ozogamicin Versus Investigator's Choice Of Chemotherapy In Patients With Relapsed Or Refractory Acute Lymphoblastic Leukemia
Scientific 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)
Secondary ID [1] 0 0
2011-005491-41
Secondary ID [2] 0 0
B1931022
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Acute Lymphoblastic Leukemia 0 0
Condition category
Condition code
Cancer 0 0 0 0
Leukaemia - Acute leukaemia
Cancer 0 0 0 0
Leukaemia - Chronic leukaemia
Cancer 0 0 0 0
Children's - Leukaemia & Lymphoma
Cancer 0 0 0 0
Lymphoma (non Hodgkin's lymphoma) - High grade lymphoma
Cancer 0 0 0 0
Lymphoma (non Hodgkin's lymphoma) - Low grade lymphoma

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - inotuzumab ozogamicin
Treatment: Drugs - FLAG (fludarabine, cytarabine and G-CSF)
Treatment: Drugs - HIDAC (high dose cytarabine)
Treatment: Drugs - cytarabine and mitoxantrone

Experimental: Arm A -

Active comparator: Arm B -


Treatment: Drugs: 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

Treatment: Drugs: 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

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

Treatment: Drugs: 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
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Percentage of Participants With Hematologic Remission (Complete Remission [CR]/Complete Remission With Incomplete Hematologic Recovery [CRi]) as Assessed by the Endpoint Adjudication Committee (EAC)
Timepoint [1] 0 0
Screening, Day 16 to 28 of Cycles 1, 2 and 3, then every 1 to 2 cycles (or as clinically indicated) up to approximately 4 weeks (end of treatment [EoT]) from the last dose
Primary outcome [2] 0 0
Overall Survival (OS)
Timepoint [2] 0 0
Up to 5 years after randomization or 2 years from randomization of the last participant, whichever occurs first.
Secondary outcome [1] 0 0
Duration of Remission (DoR) for Participants Who Achieved CR/CRi (Per Investigator Assessment)
Timepoint [1] 0 0
Up to 2 years from randomization
Secondary outcome [2] 0 0
Progression-Free Survival (PFS)
Timepoint [2] 0 0
Up to 2 years from randomization
Secondary outcome [3] 0 0
Percentage of Participants Who Had a Hematopoietic Stem-Cell Transplant (HSCT)
Timepoint [3] 0 0
Up to 19 weeks from last dose
Secondary outcome [4] 0 0
Percentage of Participants Achieving MRD Negativity (Based on Central Laboratory Analysis) in Participants Achieving a CR/CRi (Per EAC Assessment)
Timepoint [4] 0 0
Up to approximately 4 weeks (EoT) from last dose of study drug
Secondary outcome [5] 0 0
Cytogenetic Status (Based on Local Laboratory Analysis) of Participants With CR/CRi (Per EAC Assessment)
Timepoint [5] 0 0
Up to approximately 4 weeks (EoT) from last dose of study drug
Secondary outcome [6] 0 0
Maximum Observed Inotuzumab Ozogamicin Serum Concentration (Cmax) and Pre-Dose Inotuzumab Ozogamicin Serum Concentration (Ctrough) Following Single and Multiple Dosing
Timepoint [6] 0 0
Days 1, 4, 8, and 15 of Cycle 1, Days 1 and 8 of Cycle 2 and Day 1 of Cycle 4
Secondary outcome [7] 0 0
Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire, Core 30 (EORTC QLQ-C30) Score
Timepoint [7] 0 0
Day 1 of each cycle prior to dosing and EoT
Secondary outcome [8] 0 0
Change From Baseline in EuroQol 5 Dimension Health Questionnaire (EQ-5D) Index Score
Timepoint [8] 0 0
Day 1 of each cycle prior to dosing and EoT
Secondary outcome [9] 0 0
Change From Baseline in EQ-5D VAS
Timepoint [9] 0 0
Day 1 of each cycle prior to dosing and EoT
Secondary outcome [10] 0 0
Percentage of Participants With Veno-Occlusive Liver Disease (VOD)/Sinusoidal Obstruction Syndrome (SOS) Following Post Study HSCT
Timepoint [10] 0 0
Up to 2 years from randomization

Eligibility
Key inclusion criteria
* CD22 expression
* Adequate liver and renal functions
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* Isolated extramedullary disease
* Active Central Nervous System [CNS] disease

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
2/08/2012
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
4/01/2017
Sample size
Target
Accrual to date
Final
326
Recruitment in Australia
Recruitment state(s)
SA,VIC
Recruitment hospital [1] 0 0
Royal Adelaide Hospital - Adelaide
Recruitment hospital [2] 0 0
Eastern Clinical Research Unit, Box Hill Hospital - Box Hill
Recruitment postcode(s) [1] 0 0
5000 - Adelaide
Recruitment postcode(s) [2] 0 0
3128 - Box Hill
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Colorado
Country [3] 0 0
United States of America
State/province [3] 0 0
Connecticut
Country [4] 0 0
United States of America
State/province [4] 0 0
Florida
Country [5] 0 0
United States of America
State/province [5] 0 0
Georgia
Country [6] 0 0
United States of America
State/province [6] 0 0
Illinois
Country [7] 0 0
United States of America
State/province [7] 0 0
Iowa
Country [8] 0 0
United States of America
State/province [8] 0 0
Kansas
Country [9] 0 0
United States of America
State/province [9] 0 0
Kentucky
Country [10] 0 0
United States of America
State/province [10] 0 0
Maryland
Country [11] 0 0
United States of America
State/province [11] 0 0
Massachusetts
Country [12] 0 0
United States of America
State/province [12] 0 0
Michigan
Country [13] 0 0
United States of America
State/province [13] 0 0
New Jersey
Country [14] 0 0
United States of America
State/province [14] 0 0
New Mexico
Country [15] 0 0
United States of America
State/province [15] 0 0
New York
Country [16] 0 0
United States of America
State/province [16] 0 0
North Carolina
Country [17] 0 0
United States of America
State/province [17] 0 0
Ohio
Country [18] 0 0
United States of America
State/province [18] 0 0
Oklahoma
Country [19] 0 0
United States of America
State/province [19] 0 0
Pennsylvania
Country [20] 0 0
United States of America
State/province [20] 0 0
South Carolina
Country [21] 0 0
United States of America
State/province [21] 0 0
Texas
Country [22] 0 0
United States of America
State/province [22] 0 0
Utah
Country [23] 0 0
United States of America
State/province [23] 0 0
Washington
Country [24] 0 0
United States of America
State/province [24] 0 0
West Virginia
Country [25] 0 0
Argentina
State/province [25] 0 0
Cordoba
Country [26] 0 0
Canada
State/province [26] 0 0
Ontario
Country [27] 0 0
China
State/province [27] 0 0
Guangdong
Country [28] 0 0
China
State/province [28] 0 0
Henan
Country [29] 0 0
China
State/province [29] 0 0
Jilin
Country [30] 0 0
China
State/province [30] 0 0
Beijing
Country [31] 0 0
China
State/province [31] 0 0
Tianjin
Country [32] 0 0
Czechia
State/province [32] 0 0
Brno
Country [33] 0 0
Czechia
State/province [33] 0 0
Hradec Kralove
Country [34] 0 0
Czechia
State/province [34] 0 0
Praha 10
Country [35] 0 0
Finland
State/province [35] 0 0
Helsinki
Country [36] 0 0
France
State/province [36] 0 0
Dijon
Country [37] 0 0
France
State/province [37] 0 0
Grenoble Cedex 09
Country [38] 0 0
France
State/province [38] 0 0
Le Chesnay Cedex
Country [39] 0 0
France
State/province [39] 0 0
Limoges Cedex
Country [40] 0 0
France
State/province [40] 0 0
Marseille
Country [41] 0 0
France
State/province [41] 0 0
Paris Cedex 10
Country [42] 0 0
France
State/province [42] 0 0
Pierre Benite Cedex
Country [43] 0 0
France
State/province [43] 0 0
Saint Priest en Jarez Cedex
Country [44] 0 0
France
State/province [44] 0 0
Toulouse Cedex 9
Country [45] 0 0
France
State/province [45] 0 0
Vandoeuvre-les-Nancy
Country [46] 0 0
Germany
State/province [46] 0 0
Nordrhein-westfalen
Country [47] 0 0
Germany
State/province [47] 0 0
Frankfurt
Country [48] 0 0
Germany
State/province [48] 0 0
Heidelberg
Country [49] 0 0
Germany
State/province [49] 0 0
Köln
Country [50] 0 0
Germany
State/province [50] 0 0
Muenchen
Country [51] 0 0
Germany
State/province [51] 0 0
Muenster
Country [52] 0 0
Hungary
State/province [52] 0 0
Budapest
Country [53] 0 0
Hungary
State/province [53] 0 0
Debrecen
Country [54] 0 0
Italy
State/province [54] 0 0
CA
Country [55] 0 0
Italy
State/province [55] 0 0
FC
Country [56] 0 0
Italy
State/province [56] 0 0
Bologna
Country [57] 0 0
Italy
State/province [57] 0 0
Catania
Country [58] 0 0
Italy
State/province [58] 0 0
Cona, Ferrara
Country [59] 0 0
Italy
State/province [59] 0 0
Genova
Country [60] 0 0
Italy
State/province [60] 0 0
Milano
Country [61] 0 0
Italy
State/province [61] 0 0
Monza
Country [62] 0 0
Italy
State/province [62] 0 0
Napoli
Country [63] 0 0
Italy
State/province [63] 0 0
Pavia
Country [64] 0 0
Italy
State/province [64] 0 0
Ravenna
Country [65] 0 0
Italy
State/province [65] 0 0
Udine
Country [66] 0 0
Japan
State/province [66] 0 0
Aichi
Country [67] 0 0
Japan
State/province [67] 0 0
Hyogo
Country [68] 0 0
Japan
State/province [68] 0 0
Miyagi
Country [69] 0 0
Japan
State/province [69] 0 0
Osaka
Country [70] 0 0
Japan
State/province [70] 0 0
Tokyo
Country [71] 0 0
Japan
State/province [71] 0 0
Akita
Country [72] 0 0
Japan
State/province [72] 0 0
Fukuoka
Country [73] 0 0
Japan
State/province [73] 0 0
Kanagawa
Country [74] 0 0
Korea, Republic of
State/province [74] 0 0
Jeonnam
Country [75] 0 0
Korea, Republic of
State/province [75] 0 0
Seoul
Country [76] 0 0
Netherlands
State/province [76] 0 0
South Holland
Country [77] 0 0
Poland
State/province [77] 0 0
Gdansk
Country [78] 0 0
Poland
State/province [78] 0 0
Lodz
Country [79] 0 0
Poland
State/province [79] 0 0
Warsaw
Country [80] 0 0
Poland
State/province [80] 0 0
Wroclaw
Country [81] 0 0
Singapore
State/province [81] 0 0
Singapore
Country [82] 0 0
Spain
State/province [82] 0 0
Barcelona
Country [83] 0 0
Spain
State/province [83] 0 0
Castille AND LION
Country [84] 0 0
Spain
State/province [84] 0 0
Catalonia
Country [85] 0 0
Spain
State/province [85] 0 0
Mallorca
Country [86] 0 0
Spain
State/province [86] 0 0
Madrid
Country [87] 0 0
Spain
State/province [87] 0 0
Murcia
Country [88] 0 0
Spain
State/province [88] 0 0
Sevilla
Country [89] 0 0
Spain
State/province [89] 0 0
Valencia
Country [90] 0 0
Sweden
State/province [90] 0 0
Lund
Country [91] 0 0
Sweden
State/province [91] 0 0
Stockholm
Country [92] 0 0
Taiwan
State/province [92] 0 0
Kaohsiung
Country [93] 0 0
Taiwan
State/province [93] 0 0
Taipei
Country [94] 0 0
United Kingdom
State/province [94] 0 0
Hampshire
Country [95] 0 0
United Kingdom
State/province [95] 0 0
Bristol
Country [96] 0 0
United Kingdom
State/province [96] 0 0
Hull
Country [97] 0 0
United Kingdom
State/province [97] 0 0
London
Country [98] 0 0
United Kingdom
State/province [98] 0 0
Manchester
Country [99] 0 0
United Kingdom
State/province [99] 0 0
Nottingham
Country [100] 0 0
United Kingdom
State/province [100] 0 0
Oxford

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Pfizer
Address
Country
Other collaborator category [1] 0 0
Commercial sector/industry
Name [1] 0 0
UCB Pharma
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/study/NCT01564784
Trial related presentations / publications
Stelljes M, Advani AS, DeAngelo DJ, Wang T, Neuhof A, Vandendries E, Kantarjian H, Jabbour E. Time to First Subsequent Salvage Therapy in Patients With Relapsed/Refractory Acute Lymphoblastic Leukemia Treated With Inotuzumab Ozogamicin in the Phase III INO-VATE Trial. Clin Lymphoma Myeloma Leuk. 2022 Sep;22(9):e836-e843. doi: 10.1016/j.clml.2022.04.022. Epub 2022 Apr 27.
Shi Z, Zhu Y, Zhang J, Chen B. Monoclonal antibodies: new chance in the management of B-cell acute lymphoblastic leukemia. Hematology. 2022 Dec;27(1):642-652. doi: 10.1080/16078454.2022.2074704.
Kantarjian HM, Stock W, Cassaday RD, DeAngelo DJ, Jabbour E, O'Brien SM, Stelljes M, Wang T, Paccagnella ML, Nguyen K, Sleight B, Vandendries E, Neuhof A, Laird AD, Advani AS. Inotuzumab Ozogamicin for Relapsed/Refractory Acute Lymphoblastic Leukemia in the INO-VATE Trial: CD22 Pharmacodynamics, Efficacy, and Safety by Baseline CD22. Clin Cancer Res. 2021 May 15;27(10):2742-2754. doi: 10.1158/1078-0432.CCR-20-2399. Epub 2021 Feb 18.
Stock W, Martinelli G, Stelljes M, DeAngelo DJ, Gokbuget N, Advani AS, O'Brien S, Liedtke M, Merchant AA, Cassaday RD, Wang T, Zhang H, Vandendries E, Jabbour E, Marks DI, Kantarjian HM. Efficacy of inotuzumab ozogamicin in patients with Philadelphia chromosome-positive relapsed/refractory acute lymphoblastic leukemia. Cancer. 2021 Mar 15;127(6):905-913. doi: 10.1002/cncr.33321. Epub 2020 Nov 24.
DeAngelo DJ, Advani AS, Marks DI, Stelljes M, Liedtke M, Stock W, Gokbuget N, Jabbour E, Merchant A, Wang T, Vandendries E, Neuhof A, Kantarjian H, O'Brien S. Inotuzumab ozogamicin for relapsed/refractory acute lymphoblastic leukemia: outcomes by disease burden. Blood Cancer J. 2020 Aug 7;10(8):81. doi: 10.1038/s41408-020-00345-8.
Jabbour E, Gokbuget N, Advani A, Stelljes M, Stock W, Liedtke M, Martinelli G, O'Brien S, Wang T, Laird AD, Vandendries E, Neuhof A, Nguyen K, Dakappagari N, DeAngelo DJ, Kantarjian H. Impact of minimal residual disease status in patients with relapsed/refractory acute lymphoblastic leukemia treated with inotuzumab ozogamicin in the phase III INO-VATE trial. Leuk Res. 2020 Jan;88:106283. doi: 10.1016/j.leukres.2019.106283. Epub 2019 Nov 25.
Fujishima N, Uchida T, Onishi Y, Jung CW, Goh YT, Ando K, Wang MC, Ono C, Matsumizu M, Paccagnella ML, Sleight B, Vandendries E, Fujii Y, Hino M. Inotuzumab ozogamicin versus standard of care in Asian patients with relapsed/refractory acute lymphoblastic leukemia. Int J Hematol. 2019 Dec;110(6):709-722. doi: 10.1007/s12185-019-02749-0. Epub 2019 Nov 13.
Kantarjian HM, DeAngelo DJ, Stelljes M, Liedtke M, Stock W, Gokbuget N, O'Brien SM, Jabbour E, Wang T, Liang White J, Sleight B, Vandendries E, Advani AS. Inotuzumab ozogamicin versus standard of care in relapsed or refractory acute lymphoblastic leukemia: Final report and long-term survival follow-up from the randomized, phase 3 INO-VATE study. Cancer. 2019 Jul 15;125(14):2474-2487. doi: 10.1002/cncr.32116. Epub 2019 Mar 28.
Jabbour EJ, DeAngelo DJ, Stelljes M, Stock W, Liedtke M, Gokbuget N, O'Brien S, Wang T, Paccagnella ML, Sleight B, Vandendries E, Advani AS, Kantarjian HM. Efficacy and safety analysis by age cohort of inotuzumab ozogamicin in patients with relapsed or refractory acute lymphoblastic leukemia enrolled in INO-VATE. Cancer. 2018 Apr 15;124(8):1722-1732. doi: 10.1002/cncr.31249. Epub 2018 Jan 30.
Kebriaei P, Cutler C, de Lima M, Giralt S, Lee SJ, Marks D, Merchant A, Stock W, van Besien K, Stelljes M. Management of important adverse events associated with inotuzumab ozogamicin: expert panel review. Bone Marrow Transplant. 2018 Apr;53(4):449-456. doi: 10.1038/s41409-017-0019-y. Epub 2018 Jan 12.
Kantarjian HM, DeAngelo DJ, Advani AS, Stelljes M, Kebriaei P, Cassaday RD, Merchant AA, Fujishima N, Uchida T, Calbacho M, Ejduk AA, O'Brien SM, Jabbour EJ, Zhang H, Sleight BJ, Vandendries ER, Marks DI. Hepatic adverse event profile of inotuzumab ozogamicin in adult patients with relapsed or refractory acute lymphoblastic leukaemia: results from the open-label, randomised, phase 3 INO-VATE study. Lancet Haematol. 2017 Aug;4(8):e387-e398. doi: 10.1016/S2352-3026(17)30103-5. Epub 2017 Jul 4.
Kantarjian HM, DeAngelo DJ, Stelljes M, Martinelli G, Liedtke M, Stock W, Gokbuget N, O'Brien S, Wang K, Wang T, Paccagnella ML, Sleight B, Vandendries E, Advani AS. Inotuzumab Ozogamicin versus Standard Therapy for Acute Lymphoblastic Leukemia. N Engl J Med. 2016 Aug 25;375(8):740-53. doi: 10.1056/NEJMoa1509277. Epub 2016 Jun 12.
Public notes

Contacts
Principal investigator
Name 0 0
Pfizer CT.gov Call Center
Address 0 0
Pfizer
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT01564784