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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT02677922




Registration number
NCT02677922
Ethics application status
Date submitted
5/02/2016
Date registered
9/02/2016
Date last updated
25/01/2024

Titles & IDs
Public title
A Study to Assess the Safety and Efficacy of Two Combinations of Isocitrate Dehydrogenase (IDH) Mutant Targeted Therapies Plus Azacitidine in Participants With Newly Diagnosed Acute Myeloid Leukemia (AML) Harboring IDH Mutations Who Are Not Candidates to Receive Intensive Induction Chemotherapy
Scientific title
A Phase 1b/2 Open-Label, Randomized Study of 2 Combinations of Isocitrate Dehydrogenase (IDH) Mutant Targeted Therapies Plus Azacitidine: Oral AG-120 Plus Subcutaneous Azacitidine and Oral AG-221 Plus SC Azacitidine in Subjects With Newly Diagnosed Acute Myeloid Leukemia Harboring an IDH1 or an IDH2 Mutation, Respectively, Who Are Not Candidates to Receive Intensive Induction Chemotherapy
Secondary ID [1] 0 0
2015-003951-23
Secondary ID [2] 0 0
AG-221-AML-005
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Leukemia, Myeloid, Acute 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

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - AG-120
Treatment: Drugs - Azacitidine
Treatment: Drugs - AG-221

Experimental: AG-120 + Azacitidine -

Experimental: AG-221 + Azacitidine -

Experimental: Azacitidine -


Treatment: Drugs: AG-120
Specified dose on specified days

Treatment: Drugs: Azacitidine
Specified dose on specified days

Treatment: Drugs: AG-221
Specified dose on specified days
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
The Number of Participants Experiencing Dose-limiting Toxicities (DLTs): Phase 1B (Dose Finding Stage)
Timepoint [1] 0 0
From first dose to 28 days after first dose
Primary outcome [2] 0 0
The Number of Participants Experiencing Adverse Events: Phase 1B (Dose Finding and Expansion Stage)
Timepoint [2] 0 0
From first dose to 28 days after last dose (up to approximately 13 months)
Primary outcome [3] 0 0
Overall Response Rate: Phase 2 (Randomized Stage)
Timepoint [3] 0 0
From first dose up to approximately 26 months
Secondary outcome [1] 0 0
Overall Response Rate: Phase 1B (Dose Finding and Expansion Stage)
Timepoint [1] 0 0
From first dose up to approximately 13 months
Secondary outcome [2] 0 0
Sponsor Derived CR and CRh: Phase 1B (Dose Finding and Expansion Stage)
Timepoint [2] 0 0
From first dose up to approximately 13 months
Secondary outcome [3] 0 0
Event-free Survival (EFS): Phase 2 (Randomized Stage)
Timepoint [3] 0 0
From randomization to the date of documented relapse, progression, or death due to any cause, whichever occurs first (up to approximately 26 months)
Secondary outcome [4] 0 0
The Number of Participants Experiencing Adverse Events: Phase 2 (Randomized Stage)
Timepoint [4] 0 0
From first dose to 28 days after last dose (up to approximately 26 months)
Secondary outcome [5] 0 0
Complete Remission Rate: Phase 2 (Randomized Stage)
Timepoint [5] 0 0
From first dose up to approximately 26 months
Secondary outcome [6] 0 0
Hematologic Improvement (HI) Rate: Phase 2 (Randomized Stage)
Timepoint [6] 0 0
From first dose up to approximately 26 months
Secondary outcome [7] 0 0
Duration of Response: Phase 2 (Randomized Stage)
Timepoint [7] 0 0
From first dose up to approximately 26 months
Secondary outcome [8] 0 0
Time to Response: Phase 2 (Randomized Stage)
Timepoint [8] 0 0
From first dose to to first documented MLFS/CR/CRi/CRp/PR (up to approximately 26 months)
Secondary outcome [9] 0 0
Overall Survival: Phase 2 (Randomized Stage)
Timepoint [9] 0 0
From randomization to date of death (up to approximately 26 months)
Secondary outcome [10] 0 0
One Year Survival Rate: Phase 2 (Randomized Stage)
Timepoint [10] 0 0
From randomization to 1 year after randomization
Secondary outcome [11] 0 0
AUC (0-8)- Area Under the Plasma Concentration-Time Curve: Phase 1B (Expansion Stage)
Timepoint [11] 0 0
Pre-dose, 0.5, 2, 3, 4, 6, 8 hours post dose (± 10 minutes) on day 1 of cycle 1 and 2
Secondary outcome [12] 0 0
Cmax- Maximum Observed Plasma Concentration: Phase 1B (Expansion Stage)
Timepoint [12] 0 0
Pre-dose, 0.5, 2, 3, 4, 6, 8 hours post dose (± 10 minutes) on day 1 of cycle 1 and 2
Secondary outcome [13] 0 0
Tmax- Time of Maximum Observed Plasma Concentration: Phase 1B (Expansion Stage)
Timepoint [13] 0 0
Pre-dose, 0.5, 2, 3, 4, 6, 8 hours post dose (± 10 minutes) on day 1 of cycle 1 and 2
Secondary outcome [14] 0 0
AUC (0-8)- Area Under the Plasma Concentration-Time Curve: Phase 2 (Randomized Stage)
Timepoint [14] 0 0
Pre-dose, 2, 3, 4, 6, and 8 hours post dose (± 10 minutes) on day 1 of cycle 2
Secondary outcome [15] 0 0
AUC (0-24)- Area Under the Plasma Concentration-Time Curve: Phase 2 (Randomized Stage)
Timepoint [15] 0 0
Pre-dose, 2, 3, 4, 6, 8, and 24 hours post dose (± 10 minutes) on day 1 of cycle 2
Secondary outcome [16] 0 0
Cmax- Maximum Observed Plasma Concentration: Phase 2 (Randomized Stage)
Timepoint [16] 0 0
Pre-dose, 2, 3, 4, 6, 8, and 24 hours post dose (± 10 minutes) on day 1 of cycle 2
Secondary outcome [17] 0 0
Tmax- Time of Maximum Observed Plasma Concentration: Phase 2 (Randomized Stage)
Timepoint [17] 0 0
Pre-dose, 2, 3, 4, 6, 8, and 24 hours post dose (± 10 minutes) on day 1 of cycle 2
Secondary outcome [18] 0 0
Change From Baseline in Health-related Quality-of-Life Domain Scores of the EORTC QLQ-C30: Phase 2 (Randomized Stage)
Timepoint [18] 0 0
Baseline and Day 1 Cycle 5
Secondary outcome [19] 0 0
Change From Baseline in Health Utility Indices of the EQ-5D-5L: Phase 2 (Randomized Stage)
Timepoint [19] 0 0
Baseline and Day 1 Cycle 5
Secondary outcome [20] 0 0
Change From Baseline in Visual Analogue Scale (VAS) Scores of the EQ-5D-5L: Phase 2 (Randomized Stage)
Timepoint [20] 0 0
Baseline and Day 1 Cycle 5
Secondary outcome [21] 0 0
Sponsor Derived CR: Phase 2 (Randomized Stage)
Timepoint [21] 0 0
From first dose to end of study
Secondary outcome [22] 0 0
Sponsor Derived CR and CRh: Phase 2 (Randomized Phase)
Timepoint [22] 0 0
From first dose to end of study
Secondary outcome [23] 0 0
Time to Sponsor Derived CR and CRh: Phase 2 (Randomized Phase)
Timepoint [23] 0 0
From first dose to end of study
Secondary outcome [24] 0 0
Duration of Sponsor Derived CR/CRh: Phase 2 (Randomized Stage)
Timepoint [24] 0 0
From first dose to end of study

Eligibility
Key inclusion criteria
* Newly diagnosed, primary (ie, de novo) or secondary (progression of Myelodysplastic syndrome [MDS] or myeloproliferative neoplasms [MPN], or therapy-related) acute myeloid leukemia (AML) according to the WHO classification with = 20% leukemic blasts in the bone marrow
* Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2
* Agree to serial bone marrow aspirate/biopsies
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* Suspected or proven to have acute promyelocytic leukemia based on morphology, immunophenotype, molecular assay, or karyotype
* AML secondary to chronic myelogenous leukemia (CML)
* Received a targeted agent against an isocitrate dehydrogenase 1 (IDH1) or isocitrate dehydrogenase 2 (IDH2) mutation
* Has or is suspected of having central nervous system (CNS) leukemia. Evaluation of cerebrospinal fluid is only required if CNS involvement by leukemia is suspected during screening

Other protocol defined inclusion/exclusion criteria apply

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 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Active, not recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
3/06/2016
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
31/10/2024
Actual
Sample size
Target
Accrual to date
Final
130
Recruitment in Australia
Recruitment state(s)
SA
Recruitment hospital [1] 0 0
Local Institution - 178 - Adelaide
Recruitment hospital [2] 0 0
Local Institution - 175 - Melbourne
Recruitment hospital [3] 0 0
Local Institution - 177 - Perth
Recruitment postcode(s) [1] 0 0
SA 5000 - Adelaide
Recruitment postcode(s) [2] 0 0
3141 - Melbourne
Recruitment postcode(s) [3] 0 0
6000 - Perth
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
Connecticut
Country [3] 0 0
United States of America
State/province [3] 0 0
Illinois
Country [4] 0 0
United States of America
State/province [4] 0 0
Massachusetts
Country [5] 0 0
United States of America
State/province [5] 0 0
New York
Country [6] 0 0
United States of America
State/province [6] 0 0
Texas
Country [7] 0 0
Belgium
State/province [7] 0 0
Yvoir
Country [8] 0 0
Canada
State/province [8] 0 0
Ontario
Country [9] 0 0
France
State/province [9] 0 0
Lille
Country [10] 0 0
France
State/province [10] 0 0
Marseille Cedex 9
Country [11] 0 0
France
State/province [11] 0 0
Paris Cedex 10
Country [12] 0 0
France
State/province [12] 0 0
Pessac
Country [13] 0 0
France
State/province [13] 0 0
Pierre Benite
Country [14] 0 0
France
State/province [14] 0 0
Toulouse
Country [15] 0 0
France
State/province [15] 0 0
Villejuif CEDEX
Country [16] 0 0
Germany
State/province [16] 0 0
Berlin
Country [17] 0 0
Germany
State/province [17] 0 0
Dresden
Country [18] 0 0
Germany
State/province [18] 0 0
Ulm
Country [19] 0 0
Italy
State/province [19] 0 0
Bologna, Emilia-Romagna
Country [20] 0 0
Italy
State/province [20] 0 0
Firenze
Country [21] 0 0
Italy
State/province [21] 0 0
Genova
Country [22] 0 0
Italy
State/province [22] 0 0
Orbassano
Country [23] 0 0
Italy
State/province [23] 0 0
Padova
Country [24] 0 0
Italy
State/province [24] 0 0
Pesaro
Country [25] 0 0
Italy
State/province [25] 0 0
Roma
Country [26] 0 0
Korea, Republic of
State/province [26] 0 0
Seoul
Country [27] 0 0
Netherlands
State/province [27] 0 0
Utrecht
Country [28] 0 0
Portugal
State/province [28] 0 0
Lisboa
Country [29] 0 0
Spain
State/province [29] 0 0
Barcelona
Country [30] 0 0
Spain
State/province [30] 0 0
Caceres
Country [31] 0 0
Spain
State/province [31] 0 0
Madrid
Country [32] 0 0
Spain
State/province [32] 0 0
Malaga
Country [33] 0 0
Spain
State/province [33] 0 0
Valencia
Country [34] 0 0
Sweden
State/province [34] 0 0
Göteborg
Country [35] 0 0
Switzerland
State/province [35] 0 0
Basel
Country [36] 0 0
Switzerland
State/province [36] 0 0
Zurich
Country [37] 0 0
United Kingdom
State/province [37] 0 0
Birmingham
Country [38] 0 0
United Kingdom
State/province [38] 0 0
Headington
Country [39] 0 0
United Kingdom
State/province [39] 0 0
London
Country [40] 0 0
United Kingdom
State/province [40] 0 0
Sutton (Surrey)

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Celgene
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
The purpose of this study are

1. to determine the recommended combination dose of AG-120 and AG-221 separately when administered with azacitidine and,
2. to investigate the safety, tolerability, and efficacy of the combinations of AG-120 with azacitidine and AG-221 with azacitidine versus with azacitidine alone in participants with acute myeloid leukemia (AML) with the isocitrate dehydrogenase (IDH) enzyme isoforms 1 or 2 mutations, respectively.
Trial website
https://clinicaltrials.gov/study/NCT02677922
Trial related presentations / publications
DiNardo CD, Schuh AC, Stein EM, Montesinos P, Wei AH, de Botton S, Zeidan AM, Fathi AT, Kantarjian HM, Bennett JM, Frattini MG, Martin-Regueira P, Lersch F, Gong J, Hasan M, Vyas P, Dohner H. Enasidenib plus azacitidine versus azacitidine alone in patients with newly diagnosed, mutant-IDH2 acute myeloid leukaemia (AG221-AML-005): a single-arm, phase 1b and randomised, phase 2 trial. Lancet Oncol. 2021 Nov;22(11):1597-1608. doi: 10.1016/S1470-2045(21)00494-0. Epub 2021 Oct 18.
DiNardo CD, Stein AS, Stein EM, Fathi AT, Frankfurt O, Schuh AC, Dohner H, Martinelli G, Patel PA, Raffoux E, Tan P, Zeidan AM, de Botton S, Kantarjian HM, Stone RM, Frattini MG, Lersch F, Gong J, Gianolio DA, Zhang V, Franovic A, Fan B, Goldwasser M, Daigle S, Choe S, Wu B, Winkler T, Vyas P. Mutant Isocitrate Dehydrogenase 1 Inhibitor Ivosidenib in Combination With Azacitidine for Newly Diagnosed Acute Myeloid Leukemia. J Clin Oncol. 2021 Jan 1;39(1):57-65. doi: 10.1200/JCO.20.01632. Epub 2020 Oct 29. Erratum In: J Clin Oncol. 2021 Feb 1;39(4):341. doi: 10.1200/JCO.20.03658.
Public notes

Contacts
Principal investigator
Name 0 0
Bristol-Myers Squibb
Address 0 0
Bristol-Myers Squibb
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/NCT02677922