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

• ClinicalTrials.gov Identifier: NCT02677922
• Recruitment Status: Active, not recruiting
• First Posted: February 9, 2016
• Results First Posted: November 22, 2022
• Last Update Posted: January 25, 2024
• Sponsor: Celgene
• Information provided by (Responsible Party): Celgene

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Leukemia, Myeloid, Acute	Drug: AG-120; Drug: Azacitidine; Drug: AG-221	Phase 1; Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 130 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official 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
• Actual Study Start Date: June 3, 2016
• Actual Primary Completion Date: August 2, 2018
• Estimated Study Completion Date: October 31, 2024

Arms and Interventions

Arm	Intervention/treatment
Experimental: AG-120 + Azacitidine	Drug: AG-120; Specified dose on specified days; Drug: Azacitidine; Specified dose on specified days
Experimental: AG-221 + Azacitidine	Drug: Azacitidine; Specified dose on specified days; Drug: AG-221; Specified dose on specified days
Experimental: Azacitidine	Drug: Azacitidine; Specified dose on specified days

Outcome Measures

Primary Outcome Measures :

1. The Number of Participants Experiencing Dose-limiting Toxicities (DLTs): Phase 1B (Dose Finding Stage) [ Time Frame: From first dose to 28 days after first dose ]
   Dose-limiting toxicities (DLTs) are defined as an event that constitute a change from baseline irrespective of outcome and determined by the investigator to be related to treatment. The DLT-evaluable participants were defined as participants who took at least 1 dose of study drug in the Phase 1b Dose-Finding Stage and either had a DLT during Cycle 1 (regardless of amount of study drug exposure), or had no DLT and completed at least 75% of AG-120 or AG-221 doses (21 out of 28 days) and a minimum of 5 doses of AZA, at least 50% of the planned combination doses for AG-120 or AG-221 and AZA administered together (in the same day for 4 out of 7 days) in the first 28 days from C1D1, and were also considered by the Clinical Study Team to have sufficient safety data available to conclude that a DLT did not occur during Cycle 1.
2. The Number of Participants Experiencing Adverse Events: Phase 1B (Dose Finding and Expansion Stage) [ Time Frame: From first dose to 28 days after last dose (up to approximately 13 months) ]
   The number of participants experiencing different types of adverse events (AE). An AE is any noxious, unintended, or untoward medical occurrence that may appear or worsen in a participant during the course of a study. A Serious Adverse Event (SAE) is any AE occurring at any dose that: results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, and/or constitutes an important medical event. Adverse events were analyzed in terms of treatment-emergent AEs (TEAEs). Treatment-emergent adverse events (TEAE) was defined as events that began on or after the start of study drug through 28 days after the last study treatment. The severity/intensity of AEs were graded based upon the Common Terminology Criteria for Adverse Events (CTCAE, Version 4.03) where Grade 3 = Severe, Grade 4 = Life-threatening, and Grade 5 = Death.
3. Overall Response Rate: Phase 2 (Randomized Stage) [ Time Frame: From first dose up to approximately 26 months ]
   The percent of participants with MLFS + CR + CRi + CRp + PR according to modified International Working Group Acute Myeloid Leukemia (IWG AML) response criteria as assessed by investigator. Complete response (CR) and morphologic leukemia-free state (MLFS) are defined as <5% blasts in a BM aspirate sample with marrow spicules and a count of ≥200 nucleated cells. There should be no blasts with Auer rods and no extramedullary disease. CR must also include: absolute neutrophil count (ANC) ≥1,000/μL, Platelet count ≥100,000/μL, and independent of red cell transfusions for ≥1 week before each response assessment. Complete remission with incomplete neutrophil recovery (CRi) is all criteria of CR except ANC. Complete remission with incomplete platelet recovery (CRp) is all criteria of CR except platelet count. Partial remission (PR) is defined as all hematologic criteria of CR with a >50% decrease in the percentage of BM blasts to 5% to 25%. (<5% considered if Auer rods are present).

Secondary Outcome Measures :

1. Overall Response Rate: Phase 1B (Dose Finding and Expansion Stage) [ Time Frame: From first dose up to approximately 13 months ]
   Percent of participants with MLFS + CR + CRi + CRp + PR according to modified International Working Group Acute Myeloid Leukemia (IWG AML) response criteria as assessed by investigator. Complete response (CR) and morphologic leukemia-free state (MLFS) are defined as <5% blasts in a BM aspirate sample with marrow spicules and a count of ≥200 nucleated cells. There should be no blasts with Auer rods and no extramedullary disease. CR must also include: absolute neutrophil count (ANC) ≥1,000/μL, Platelet count ≥100,000/μL, and independent of red cell transfusions for ≥1 week before each response assessment. Complete remission with incomplete neutrophil recovery (CRi) is all criteria of CR except ANC. Complete remission with incomplete platelet recovery (CRp) is all criteria of CR except platelet count. Partial remission (PR) is defined as all hematologic criteria of CR with a >50% decrease in the percentage of BM blasts to 5% to 25%. (<5% considered if Auer rods are present).
2. Sponsor Derived CR and CRh: Phase 1B (Dose Finding and Expansion Stage) [ Time Frame: From first dose up to approximately 13 months ]
   The percent of participants with morphologic complete remission (CR) and morphologic complete remission with partial hematologic recovery (CRh) based on laboratory data. CR is defined as less than 5% blasts in a BM aspirate sample with marrow spicules and with a count of at least 200 nucleated cells. There should be no blasts with Auer rods and absence of extramedullary disease. Plus, all the following conditions should be met: ANC ≥ 1 x 109/L (1,000/μL), platelet count ≥ 100 x 109/L (100,000/μL), independent of red cell transfusions for ≥ 1 week immediately before each response assessment. CRh is defined as less than 5% blasts in a BM aspirate sample with marrow spicules plus ANC > 500 x 109/L (1,000/μL) & Platelet count > 50 x 109/L (100,000/μL). CRh is defined as Response of bone marrow blast <5% with absolute neutrophil count (ANC) > 0.5 × 10^9/L and platelet > 50 × 10^9/L.
3. Event-free Survival (EFS): Phase 2 (Randomized Stage) [ Time Frame: From randomization to the date of documented relapse, progression, or death due to any cause, whichever occurs first (up to approximately 26 months) ]
   Event-Free Survival is the time from date of randomization to the date of documented morphologic relapse, progression, or death from any cause, whichever occurs first. Morphologic Relapse is defined as either reappearance of ≥ 5% blasts in the BM not attributable to any other cause or the development of extramedullary disease. Progression is defined as a > 50% increase of BM blast count percentage from baseline to ≥ 20% for participants with 5 to 70% BM blasts at baseline or a doubling of absolute blast count in peripheral blood from baseline to ≥ 10 x 109/L (10,000/μL) for participants with > 70% BM blasts at baseline or the development of new extramedullary disease.
4. The Number of Participants Experiencing Adverse Events: Phase 2 (Randomized Stage) [ Time Frame: From first dose to 28 days after last dose (up to approximately 26 months) ]
   The number of participants experiencing different types of adverse events (AE). An AE is any noxious, unintended, or untoward medical occurrence that may appear or worsen in a participant during the course of a study. A Serious Adverse Event (SAE) is any AE occurring at any dose that: results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, and/or constitutes an important medical event. Adverse events were analyzed in terms of treatment-emergent AEs (TEAEs). Treatment-emergent adverse events (TEAE) was defined as events that began on or after the start of study drug through 28 days after the last study treatment. The severity/intensity of AEs were graded based upon the Common Terminology Criteria for Adverse Events (CTCAE, Version 4.03) where Grade 3 = Severe, Grade 4 = Life-threatening, and Grade 5 = Death.
5. Complete Remission Rate: Phase 2 (Randomized Stage) [ Time Frame: From first dose up to approximately 26 months ]
   The percent of participants with morphologic complete remission (CR) according to modified International Working Group Acute Myeloid Leukemia Response Criteria (IWG AML). CR is defined as less than 5% blasts in a BM aspirate sample with marrow spicules and with a count of at least 200 nucleated cells. There should be no blasts with Auer rods and absence of extramedullary disease; plus the following conditions: absolute neutrophil count (ANC) ≥1,000/μL, Platelet count ≥100,000/μL, and independent of red cell transfusions for ≥1 week before each response assessment.
6. Hematologic Improvement (HI) Rate: Phase 2 (Randomized Stage) [ Time Frame: From first dose up to approximately 26 months ]
   The percent of participants with hematologic improvement neutrophil response (HI-N) + hematologic improvement platelet response (HI-P) + hematologic improvement erythroid response (HI-E) according to the International Working Group for Myelodysplastic Syndromes for Hematologic Improvement (IWG MDS HI) criteria. HI-E is defined as a hemoglobin increase by ≥ 1.5 g/dL and a relevant reduction in units of RBC transfusions by an absolute number of at least 4 RBC transfusions/8 week compared with the pretreatment transfusion number in the previous 8 week. HI-P is defined as an absolute increase of ≥ 30 X 10^9/L for participants starting with > 20 X and an increase from < 20 X 10^9/L to > 20 X 10^9/L and by at least 100%. HI-N is defined as At least 100% increase and an absolute increase > 0.5 X 10^9/L.
7. Duration of Response: Phase 2 (Randomized Stage) [ Time Frame: From first dose up to approximately 26 months ]
   The time from first documented CR/CRi/CRp/PR/MLFS to documented morphologic relapse, progression, or death due to any cause, whichever occurred first. CR and MLFS are defined as <5% blasts in a BM aspirate sample with marrow spicules + a count of ≥200 nucleated cells with no blasts with Auer rods + no extramedullary disease. CR must also include: ANC ≥ 1,000/μL, Platelet count ≥100,000/μL, + independent of red cell transfusions for ≥1 week before assessment. CRi is all criteria of CR except ANC. CRp is all criteria of CR except platelet count. PR is defined as all hematologic criteria of CR with >50% decrease in BM blasts to 5%-25%. Relapse is defined as reappearance of ≥ 5% blasts in the BM not attributable to other cause or development of extramedullary disease. Progression is defined as > 50% increase of BM blast count from baseline to ≥ 20% or a doubling of absolute blast count in peripheral blood from baseline to ≥ 10,000/μL or development of new extramedullary disease.
8. Time to Response: Phase 2 (Randomized Stage) [ Time Frame: From first dose to to first documented MLFS/CR/CRi/CRp/PR (up to approximately 26 months) ]
   Time from first dose of study drug to first documented MLFS/CR/CRi/CRp/PR according to modified IWG AML response criteria. Complete remission (CR) and morphologic leukemia-free state (MLFS) are defined as <5% blasts in a BM aspirate sample with marrow spicules and a count of ≥200 nucleated cells. There should be no blasts with Auer rods and no extramedullary disease. CR must also include the following conditions: absolute neutrophil count (ANC) ≥1,000/μL, Platelet count ≥100,000/μL, and independent of red cell transfusions for ≥1 week before each response assessment. Complete remission with incomplete neutrophil recovery (CRi) is all criteria of CR except ANC. Complete remission with incomplete platelet recovery (CRp) is all criteria of CR except platelet count. partial remission (PR) is defined as all hematologic criteria of CR with a >50% decrease in the percentage of BM blasts to 5% to 25%. (<5% considered if Auer rods are present).
9. Overall Survival: Phase 2 (Randomized Stage) [ Time Frame: From randomization to date of death (up to approximately 26 months) ]
   Overall survival (OS) is defined as time from randomization to death due to any cause.
10. One Year Survival Rate: Phase 2 (Randomized Stage) [ Time Frame: From randomization to 1 year after randomization ]
    The percent of participants alive at 1 year from randomization
11. AUC (0-8)- Area Under the Plasma Concentration-Time Curve: Phase 1B (Expansion Stage) [ Time Frame: Pre-dose, 0.5, 2, 3, 4, 6, 8 hours post dose (± 10 minutes) on day 1 of cycle 1 and 2 ]
    Area under the plasma concentration-time curve from time zero to 8 hours, calculated using the linear trapezoid rule.
12. Cmax- Maximum Observed Plasma Concentration: Phase 1B (Expansion Stage) [ Time Frame: Pre-dose, 0.5, 2, 3, 4, 6, 8 hours post dose (± 10 minutes) on day 1 of cycle 1 and 2 ]
    Cmax: Maximum observed plasma concentration, obtained directly from the observed concentration versus time data
13. Tmax- Time of Maximum Observed Plasma Concentration: Phase 1B (Expansion Stage) [ Time Frame: Pre-dose, 0.5, 2, 3, 4, 6, 8 hours post dose (± 10 minutes) on day 1 of cycle 1 and 2 ]
    Tmax: Time of maximum observed plasma concentration, obtained directly from the observed concentration versus time data.
14. AUC (0-8)- Area Under the Plasma Concentration-Time Curve: Phase 2 (Randomized Stage) [ Time Frame: Pre-dose, 2, 3, 4, 6, and 8 hours post dose (± 10 minutes) on day 1 of cycle 2 ]
    Area under the plasma concentration-time curve from time zero to 8 hours, calculated using the linear trapezoid rule.
15. AUC (0-24)- Area Under the Plasma Concentration-Time Curve: Phase 2 (Randomized Stage) [ Time Frame: Pre-dose, 2, 3, 4, 6, 8, and 24 hours post dose (± 10 minutes) on day 1 of cycle 2 ]
    AUC0-24: Area under the plasma concentration-time curve from time zero to 24 hours, calculated using the linear trapezoid rule.
16. Cmax- Maximum Observed Plasma Concentration: Phase 2 (Randomized Stage) [ Time Frame: Pre-dose, 2, 3, 4, 6, 8, and 24 hours post dose (± 10 minutes) on day 1 of cycle 2 ]
    Cmax: Maximum observed plasma concentration, obtained directly from the observed concentration versus time data.
17. Tmax- Time of Maximum Observed Plasma Concentration: Phase 2 (Randomized Stage) [ Time Frame: Pre-dose, 2, 3, 4, 6, 8, and 24 hours post dose (± 10 minutes) on day 1 of cycle 2 ]
    Tmax: Time of maximum observed plasma concentration, obtained directly from the observed concentration versus time data.
18. Change From Baseline in Health-related Quality-of-Life Domain Scores of the EORTC QLQ-C30: Phase 2 (Randomized Stage) [ Time Frame: Baseline and Day 1 Cycle 5 ]
    The European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) is composed of 30 items that address general physical symptoms, physical functioning, fatigue and malaise, and social and emotional functioning. Subscale scores are transformed to a 0 to 100 scale, with higher scores on functional scales indicating better function and higher scores on symptom scales indicating worse symptoms. Baseline results are obtained just prior to the start of study treatment on Day 1 of Cycle 1 and will serve as the baseline values. EORTC QLQ-C30 is assessed prior to dosing and prior to interaction with study personnel.
19. Change From Baseline in Health Utility Indices of the EQ-5D-5L: Phase 2 (Randomized Stage) [ Time Frame: Baseline and Day 1 Cycle 5 ]
    The European Quality of Life 5D-5L Scale (EQ-5D-5L) assesses general health-related quality of life. Health is defined in 5 dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Each dimension has 5 levels: no problems, slight problems, moderate problems, severe problems, and extreme problems. Responses are coded so that a '1' indicates no problem, and '5' indicates the most serious problem. The responses for the 5 dimensions are combined in a 5-digit number. These health states are converted to a single index value using the crosswalk method to the EQ-5D-3L value set from the United Kingdom (UK). The EQ-5D-3L health utility index based on the UK population weights range from -0.594 to 1.0 with higher scores indicating higher health utility. Baseline results are obtained just prior to the start of study treatment on Day 1 of Cycle 1 and will serve as the baseline values.
20. Change From Baseline in Visual Analogue Scale (VAS) Scores of the EQ-5D-5L: Phase 2 (Randomized Stage) [ Time Frame: Baseline and Day 1 Cycle 5 ]
    The European Quality of Life 5D-5L (EQ-5D-5L) instrument has a respondent's self-rated today's health scale which is recorded on a VAS with endpoints labeled "the best health you can imagine" and "the worst health you can imagine." The scale is numbered from 0 to 100 with 0 corresponding to the worst imaginable health state and 100 corresponding to the best imaginable health state. A high score represents a better level of QoL. Baseline results are obtained just prior to the start of study treatment on Day 1 of Cycle 1 and will serve as the baseline values.
21. Sponsor Derived CR: Phase 2 (Randomized Stage) [ Time Frame: From first dose to end of study ]
    The number of participants with Morphologic Complete Remission (CR) based on laboratory data. CR is defined as as less than 5% blasts in a BM aspirate sample with marrow spicules and with a count of at least 200 nucleated cells. There should be no blasts with Auer rods and absence of extramedullary disease. Plus, all the following conditions should be met: ANC ≥ 1 x 109/L (1,000/μL), platelet count ≥ 100 x 109/L (100,000/μL), independent of red cell transfusions for ≥ 1 week immediately before each response assessment.
22. Sponsor Derived CR and CRh: Phase 2 (Randomized Phase) [ Time Frame: From first dose to end of study ]
    The number of participants with morphologic complete remission (CR) and morphologic complete remission with partial hematologic recovery (CRh) based on laboratory data. CR is defined as less than 5% blasts in a BM aspirate sample with marrow spicules and with a count of at least 200 nucleated cells. There should be no blasts with Auer rods and absence of extramedullary disease. Plus, all the following conditions should be met: ANC ≥ 1 x 109/L (1,000/μL), platelet count ≥ 100 x 109/L (100,000/μL), independent of red cell transfusions for ≥ 1 week immediately before each response assessment. CRh is defined as Response of bone marrow blast <5% with absolute neutrophil count (ANC) > 0.5 × 10^9/L and platelet > 50 × 10^9/L.
23. Time to Sponsor Derived CR and CRh: Phase 2 (Randomized Phase) [ Time Frame: From first dose to end of study ]
    Time from first dose of study drug to first documented CR/CRh. Morphologic Complete Remission (CR) is defined as as less than 5% blasts in a BM aspirate sample with marrow spicules and with a count of at least 200 nucleated cells. There should be no blasts with Auer rods and absence of extramedullary disease. Plus, all the following conditions should be met: ANC ≥ 1 x 109/L (1,000/μL), platelet count ≥ 100 x 109/L (100,000/μL), independent of red cell transfusions for ≥ 1 week immediately before each response assessment. Morphologic complete remission with partial hematologic recovery (CRh) is defined as less than 5% blasts in a BM aspirate sample with marrow spicules plus ANC > 500 x 109/L (1,000/μL) & Platelet count > 50 x 109/L (100,000/μL).
24. Duration of Sponsor Derived CR/CRh: Phase 2 (Randomized Stage) [ Time Frame: From first dose to end of study ]
    Time from first documented CR/CRh to documented morphologic relapse, PD, or death due to any cause, whichever occurred first. Participants without morphologic relapse, PD, or death due to any cause were censored at the date of the last response assessment. Morphologic Relapse is defined as either reappearance of ≥ 5% blasts in the BM not attributable to any other cause or the development of extramedullary disease. Progression (PD) is defined as a > 50% increase of BM blast count percentage from baseline to ≥ 20% for participants with 5 to 70% BM blasts at baseline or a doubling of absolute blast count in peripheral blood from baseline to ≥ 10 x 109/L (10,000/μL) for participants with > 70% BM blasts at baseline or the development of new extramedullary disease.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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

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

Contacts and Locations

Locations

United States, California

Local Institution - 105

Duarte, California, United States, 91010-301

United States, Connecticut

Local Institution - 107

New Haven, Connecticut, United States, 06510

United States, Illinois

Local Institution - 108

Chicago, Illinois, United States, 60611

Local Institution - 103

Chicago, Illinois, United States, 60637

United States, Massachusetts

Local Institution - 102

Boston, Massachusetts, United States, 02114

Beth Israel Deaconess Medical Center

Boston, Massachusetts, United States, 02115

Local Institution - 902

Boston, Massachusetts, United States, 02115

United States, New York

Local Institution - 106

New York, New York, United States, 10065

United States, Texas

Local Institution - 110

Dallas, Texas, United States, 75390-85520

Australia, South Australia

Local Institution - 178

Adelaide, South Australia, Australia, SA 5000

Australia

Local Institution - 175

Melbourne, Australia, 3141

Local Institution - 177

Perth, Australia, 6000

Belgium

Local Institution - UNK-121

Yvoir, Belgium, 5530

Canada, Ontario

Local Institution - 125

Toronto, Ontario, Canada, M5G 2M9

France

Local Institution - 205

Lille, France, 59037

Local Institution - 206

Marseille Cedex 9, France, 13273

Local Institution - 200

Paris Cedex 10, France, 75475

Local Institution - 204

Pessac, France, 33604

Local Institution - 202

Pierre Benite, France, 69495

Local Institution - 203

Toulouse, France, 31059

Local Institution - 201

Villejuif CEDEX, France, 94805

Germany

Local Institution - 227

Berlin, Germany, 12200

Local Institution - 230

Dresden, Germany, 01307

Local Institution - 225

Ulm, Germany, 89081

Italy

Local Institution - 253

Bologna, Emilia-Romagna, Italy, 40138

Local Institution - 252

Firenze, Italy, 50134

Local Institution - 256

Genova, Italy, 16132

Local Institution - 251

Orbassano, Italy, 10043

Local Institution - 254

Padova, Italy, 35128

Local Institution - 250

Pesaro, Italy, 31122

Local Institution - 255

Roma, Italy, 00189

Korea, Republic of

Local Institution - 351

Seoul, Korea, Republic of, 135-710

Local Institution - 350

Seoul, Korea, Republic of, 138-736

Netherlands

Local Institution - 277

Utrecht, Netherlands, 3584 CX

Portugal

Local Institution - 327

Lisboa, Portugal, 1169-050

Spain

Local Institution - 379

Barcelona, Spain, 08036

Local Institution - 375

Barcelona, Spain, 08907

Local Institution - 376

Caceres, Spain, 10005

Local Institution - 378

Madrid, Spain, 28007

Local Institution - 381

Madrid, Spain, 28033

Local Institution - 380

Malaga, Spain, 29010

Local Institution - 377

Valencia, Spain, 46009

Sweden

Local Institution - UNK-52

Göteborg, Sweden, 413 45

Switzerland

Local Institution - 403

Basel, Switzerland, 4031

Local Institution - 401

Zurich, Switzerland, 0

United Kingdom

Local Institution - 429

Birmingham, United Kingdom, B15 2TH

Local Institution - 427

Headington, United Kingdom, OX3 9DU

Local Institution - 428

London, United Kingdom, SE5 9RS

Local Institution - 430

Sutton (Surrey), United Kingdom, SM2 5PT

Sponsors and Collaborators

Celgene

Investigators

• Study Director: Bristol-Myers Squibb; Bristol-Myers Squibb

  Study Documents (Full-Text)

Documents provided by Celgene:

Study Protocol  [PDF] May 13, 2021

Statistical Analysis Plan  [PDF] March 25, 2020

More Information

Additional Information:

BMS Clinical Trial Information 

BMS Clinical Trial Patient Recruiting 

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

• Responsible Party: Celgene
• ClinicalTrials.gov Identifier: NCT02677922
• Other Study ID Numbers: AG-221-AML-005; 2015-003951-23 ( EudraCT Number )
• First Posted: February 9, 2016
• Results First Posted: November 22, 2022
• Last Update Posted: January 25, 2024
• Last Verified: January 2024

Keywords provided by Celgene:

Acute Myeloid Leukemia; Leukemia; Azacitidine; AG-120; AG-221

Additional relevant MeSH terms:

Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Azacitidine; Antimetabolites, Antineoplastic; Antimetabolites; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Enzyme Inhibitors