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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

Primary Purpose

Leukemia, Myeloid, Acute

Status

Active

Phase

Phase 1

Locations

International

Study Type

Interventional

Intervention

AG-120

Azacitidine

AG-221

About this trial

This is an interventional treatment trial for Leukemia, Myeloid, Acute focused on measuring Acute Myeloid Leukemia, Leukemia, Azacitidine, AG-120, AG-221

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Arm Label

AG-120 + Azacitidine

AG-221 + Azacitidine

Azacitidine

Arm Description

Outcomes

Primary Outcome Measures

The Number of Participants Experiencing Dose-limiting Toxicities (DLTs): Phase 1B (Dose Finding Stage)

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.

The Number of Participants Experiencing Adverse Events: Phase 1B (Dose Finding and Expansion Stage)

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.

Overall Response Rate: Phase 2 (Randomized Stage)

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

Overall Response Rate: Phase 1B (Dose Finding and Expansion Stage)

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).

Sponsor Derived CR and CRh: Phase 1B (Dose Finding and Expansion Stage)

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.

Event-free Survival (EFS): Phase 2 (Randomized Stage)

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.

The Number of Participants Experiencing Adverse Events: Phase 2 (Randomized Stage)

Complete Remission Rate: Phase 2 (Randomized Stage)

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.

Hematologic Improvement (HI) Rate: Phase 2 (Randomized Stage)

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.

Duration of Response: Phase 2 (Randomized Stage)

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.

Time to Response: Phase 2 (Randomized Stage)

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).

Overall Survival: Phase 2 (Randomized Stage)

Overall survival (OS) is defined as time from randomization to death due to any cause.

One Year Survival Rate: Phase 2 (Randomized Stage)

The percent of participants alive at 1 year from randomization

AUC (0-8)- Area Under the Plasma Concentration-Time Curve: Phase 1B (Expansion Stage)

Area under the plasma concentration-time curve from time zero to 8 hours, calculated using the linear trapezoid rule.

Cmax- Maximum Observed Plasma Concentration: Phase 1B (Expansion Stage)

Cmax: Maximum observed plasma concentration, obtained directly from the observed concentration versus time data

Tmax- Time of Maximum Observed Plasma Concentration: Phase 1B (Expansion Stage)

Tmax: Time of maximum observed plasma concentration, obtained directly from the observed concentration versus time data.

AUC (0-8)- Area Under the Plasma Concentration-Time Curve: Phase 2 (Randomized Stage)

Area under the plasma concentration-time curve from time zero to 8 hours, calculated using the linear trapezoid rule.

AUC (0-24)- Area Under the Plasma Concentration-Time Curve: Phase 2 (Randomized Stage)

AUC0-24: Area under the plasma concentration-time curve from time zero to 24 hours, calculated using the linear trapezoid rule.

Cmax- Maximum Observed Plasma Concentration: Phase 2 (Randomized Stage)

Cmax: Maximum observed plasma concentration, obtained directly from the observed concentration versus time data.

Tmax- Time of Maximum Observed Plasma Concentration: Phase 2 (Randomized Stage)

Tmax: Time of maximum observed plasma concentration, obtained directly from the observed concentration versus time data.

Change From Baseline in Health-related Quality-of-Life Domain Scores of the EORTC QLQ-C30: Phase 2 (Randomized Stage)

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.

Change From Baseline in Health Utility Indices of the EQ-5D-5L: Phase 2 (Randomized Stage)

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.

Change From Baseline in Visual Analogue Scale (VAS) Scores of the EQ-5D-5L: Phase 2 (Randomized Stage)

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.

Sponsor Derived CR: Phase 2 (Randomized Stage)

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.

Sponsor Derived CR and CRh: Phase 2 (Randomized Phase)

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.

Time to Sponsor Derived CR and CRh: Phase 2 (Randomized Phase)

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).

Duration of Sponsor Derived CR/CRh: Phase 2 (Randomized Stage)

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.

Full Information

NCT ID

NCT02677922

First Posted

February 5, 2016

Last Updated

July 20, 2023

Sponsor

Celgene

1. Study Identification

Unique Protocol Identification Number

NCT02677922

Brief 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

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

Study Type

Interventional

2. Study Status

Record Verification Date

July 2023

Overall Recruitment Status

Active, not recruiting

Study Start Date

June 3, 2016 (Actual)

Primary Completion Date

August 2, 2018 (Actual)

Study Completion Date

October 31, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Celgene

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

The purpose of this study are to determine the recommended combination dose of AG-120 and AG-221 separately when administered with azacitidine and, 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Leukemia, Myeloid, Acute

Keywords

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

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1, Phase 2

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

130 (Actual)

8. Arms, Groups, and Interventions

Arm Title

AG-120 + Azacitidine

Arm Type

Experimental

Arm Title

AG-221 + Azacitidine

Arm Type

Experimental

Arm Title

Azacitidine

Arm Type

Experimental

Intervention Type

Drug

Intervention Name(s)

AG-120

Intervention Description

Specified dose on specified days

Intervention Type

Drug

Intervention Name(s)

Azacitidine

Intervention Description

Specified dose on specified days

Intervention Type

Drug

Intervention Name(s)

AG-221

Intervention Description

Specified dose on specified days

Primary Outcome Measure Information:

Title

The Number of Participants Experiencing Dose-limiting Toxicities (DLTs): Phase 1B (Dose Finding Stage)

Description

Time Frame

From first dose to 28 days after first dose

Title

The Number of Participants Experiencing Adverse Events: Phase 1B (Dose Finding and Expansion Stage)

Description

Time Frame

From first dose to 28 days after last dose (up to approximately 13 months)

Title

Overall Response Rate: Phase 2 (Randomized Stage)

Description

Time Frame

From first dose up to approximately 26 months

Secondary Outcome Measure Information:

Title

Overall Response Rate: Phase 1B (Dose Finding and Expansion Stage)

Description

Time Frame

From first dose up to approximately 13 months

Title

Sponsor Derived CR and CRh: Phase 1B (Dose Finding and Expansion Stage)

Description

Time Frame

From first dose up to approximately 13 months

Title

Event-free Survival (EFS): Phase 2 (Randomized Stage)

Description

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)

Title

The Number of Participants Experiencing Adverse Events: Phase 2 (Randomized Stage)

Description

Time Frame

From first dose to 28 days after last dose (up to approximately 26 months)

Title

Complete Remission Rate: Phase 2 (Randomized Stage)

Description

Time Frame

From first dose up to approximately 26 months

Title

Hematologic Improvement (HI) Rate: Phase 2 (Randomized Stage)

Description

Time Frame

From first dose up to approximately 26 months

Title

Duration of Response: Phase 2 (Randomized Stage)

Description

Time Frame

From first dose up to approximately 26 months

Title

Time to Response: Phase 2 (Randomized Stage)

Description

Time Frame

From first dose to to first documented MLFS/CR/CRi/CRp/PR (up to approximately 26 months)

Title

Overall Survival: Phase 2 (Randomized Stage)

Description

Overall survival (OS) is defined as time from randomization to death due to any cause.

Time Frame

From randomization to date of death (up to approximately 26 months)

Title

One Year Survival Rate: Phase 2 (Randomized Stage)

Description

The percent of participants alive at 1 year from randomization

Time Frame

From randomization to 1 year after randomization

Title

AUC (0-8)- Area Under the Plasma Concentration-Time Curve: Phase 1B (Expansion Stage)

Description

Area under the plasma concentration-time curve from time zero to 8 hours, calculated using the linear trapezoid rule.

Time Frame

Pre-dose, 0.5, 2, 3, 4, 6, 8 hours post dose (± 10 minutes) on day 1 of cycle 1 and 2

Title

Cmax- Maximum Observed Plasma Concentration: Phase 1B (Expansion Stage)

Description

Cmax: Maximum observed plasma concentration, obtained directly from the observed concentration versus time data

Time Frame

Pre-dose, 0.5, 2, 3, 4, 6, 8 hours post dose (± 10 minutes) on day 1 of cycle 1 and 2

Title

Tmax- Time of Maximum Observed Plasma Concentration: Phase 1B (Expansion Stage)

Description

Tmax: Time of maximum observed plasma concentration, obtained directly from the observed concentration versus time data.

Time Frame

Pre-dose, 0.5, 2, 3, 4, 6, 8 hours post dose (± 10 minutes) on day 1 of cycle 1 and 2

Title

AUC (0-8)- Area Under the Plasma Concentration-Time Curve: Phase 2 (Randomized Stage)

Description

Area under the plasma concentration-time curve from time zero to 8 hours, calculated using the linear trapezoid rule.

Time Frame

Pre-dose, 2, 3, 4, 6, and 8 hours post dose (± 10 minutes) on day 1 of cycle 2

Title

AUC (0-24)- Area Under the Plasma Concentration-Time Curve: Phase 2 (Randomized Stage)

Description

AUC0-24: Area under the plasma concentration-time curve from time zero to 24 hours, calculated using the linear trapezoid rule.

Time Frame

Pre-dose, 2, 3, 4, 6, 8, and 24 hours post dose (± 10 minutes) on day 1 of cycle 2

Title

Cmax- Maximum Observed Plasma Concentration: Phase 2 (Randomized Stage)

Description

Cmax: Maximum observed plasma concentration, obtained directly from the observed concentration versus time data.

Time Frame

Pre-dose, 2, 3, 4, 6, 8, and 24 hours post dose (± 10 minutes) on day 1 of cycle 2

Title

Tmax- Time of Maximum Observed Plasma Concentration: Phase 2 (Randomized Stage)

Description

Tmax: Time of maximum observed plasma concentration, obtained directly from the observed concentration versus time data.

Time Frame

Pre-dose, 2, 3, 4, 6, 8, and 24 hours post dose (± 10 minutes) on day 1 of cycle 2

Title

Change From Baseline in Health-related Quality-of-Life Domain Scores of the EORTC QLQ-C30: Phase 2 (Randomized Stage)

Description

Time Frame

Baseline and Day 1 Cycle 5

Title

Change From Baseline in Health Utility Indices of the EQ-5D-5L: Phase 2 (Randomized Stage)

Description

Time Frame

Baseline and Day 1 Cycle 5

Title

Change From Baseline in Visual Analogue Scale (VAS) Scores of the EQ-5D-5L: Phase 2 (Randomized Stage)

Description

Time Frame

Baseline and Day 1 Cycle 5

Title

Sponsor Derived CR: Phase 2 (Randomized Stage)

Description

Time Frame

From first dose to end of study

Title

Sponsor Derived CR and CRh: Phase 2 (Randomized Phase)

Description

Time Frame

From first dose to end of study

Title

Time to Sponsor Derived CR and CRh: Phase 2 (Randomized Phase)

Description

Time Frame

From first dose to end of study

Title

Duration of Sponsor Derived CR/CRh: Phase 2 (Randomized Stage)

Description

Time Frame

From first dose to end of study

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility 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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Bristol-Myers Squibb

Organizational Affiliation

Bristol-Myers Squibb

Official's Role

Study Director

Facility Information:

Facility Name

Local Institution - 105

City

Duarte

State/Province

California

ZIP/Postal Code

91010-301

Country

United States

Facility Name

Local Institution - 107

City

New Haven

State/Province

Connecticut

ZIP/Postal Code

06510

Country

United States

Facility Name

Local Institution - 108

City

Chicago

State/Province

Illinois

ZIP/Postal Code

60611

Country

United States

Facility Name

Local Institution - 103

City

Chicago

State/Province

Illinois

ZIP/Postal Code

60637

Country

United States

Facility Name

Local Institution - 102

City

Boston

State/Province

Massachusetts

ZIP/Postal Code

02114

Country

United States

Facility Name

Beth Israel Deaconess Medical Center

City

Boston

State/Province

Massachusetts

ZIP/Postal Code

02115

Country

United States

Facility Name

Local Institution - 902

City

Boston

State/Province

Massachusetts

ZIP/Postal Code

02115

Country

United States

Facility Name

Local Institution - 106

City

New York

State/Province

New York

ZIP/Postal Code

10065

Country

United States

Facility Name

Local Institution - 110

City

Dallas

State/Province

Texas

ZIP/Postal Code

75390-85520

Country

United States

Facility Name

Local Institution - 178

City

Adelaide

State/Province

South Australia

ZIP/Postal Code

SA 5000

Country

Australia

Facility Name

Local Institution - 175

City

Melbourne

ZIP/Postal Code

3141

Country

Australia

Facility Name

Local Institution - 177

City

Perth

ZIP/Postal Code

6000

Country

Australia

Facility Name

Local Institution - 125

City

Toronto

State/Province

Ontario

ZIP/Postal Code

M5G 2M9

Country

Canada

Facility Name

Local Institution - 205

City

Lille

ZIP/Postal Code

59037

Country

France

Facility Name

Local Institution - 206

City

Marseille Cedex 9

ZIP/Postal Code

13273

Country

France

Facility Name

Local Institution - 200

City

Paris Cedex 10

ZIP/Postal Code

75475

Country

France

Facility Name

Local Institution - 204

City

Pessac

ZIP/Postal Code

33604

Country

France

Facility Name

Local Institution - 202

City

Pierre Benite

ZIP/Postal Code

69495

Country

France

Facility Name

Local Institution - 203

City

Toulouse

ZIP/Postal Code

31059

Country

France

Facility Name

Local Institution - 201

City

Villejuif CEDEX

ZIP/Postal Code

94805

Country

France

Facility Name

Local Institution - 227

City

Berlin

ZIP/Postal Code

12200

Country

Germany

Facility Name

Local Institution - 230

City

Dresden

ZIP/Postal Code

01307

Country

Germany

Facility Name

Local Institution - 253

City

Bologna, Emilia-Romagna

ZIP/Postal Code

40138

Country

Italy

Facility Name

Local Institution - 252

City

Firenze

ZIP/Postal Code

50134

Country

Italy

Facility Name

Local Institution - 256

City

Genova

ZIP/Postal Code

16132

Country

Italy

Facility Name

Local Institution - 251

City

Orbassano

ZIP/Postal Code

10043

Country

Italy

Facility Name

Local Institution - 254

City

Padova

ZIP/Postal Code

35128

Country

Italy

Facility Name

Local Institution - 250

City

Pesaro

ZIP/Postal Code

31122

Country

Italy

Facility Name

Local Institution - 255

City

Roma

ZIP/Postal Code

00189

Country

Italy

Facility Name

Local Institution - 351

City

Seoul

ZIP/Postal Code

135-710

Country

Korea, Republic of

Facility Name

Local Institution - 350

City

Seoul

ZIP/Postal Code

138-736

Country

Korea, Republic of

Facility Name

Local Institution - 277

City

Utrecht

ZIP/Postal Code

3584 CX

Country

Netherlands

Facility Name

Local Institution - 327

City

Lisboa

ZIP/Postal Code

1169-050

Country

Portugal

Facility Name

Local Institution - 379

City

Barcelona

ZIP/Postal Code

08036

Country

Spain

Facility Name

Local Institution - 375

City

Barcelona

ZIP/Postal Code

08907

Country

Spain

Facility Name

Local Institution - 376

City

Caceres

ZIP/Postal Code

10005

Country

Spain

Facility Name

Local Institution - 378

City

Madrid

ZIP/Postal Code

28007

Country

Spain

Facility Name

Local Institution - 381

City

Madrid

ZIP/Postal Code

28033

Country

Spain

Facility Name

Local Institution - 380

City

Malaga

ZIP/Postal Code

29010

Country

Spain

Facility Name

Local Institution - 377

City

Valencia

ZIP/Postal Code

46009

Country

Spain

Facility Name

Local Institution - 403

City

Basel

ZIP/Postal Code

4031

Country

Switzerland

Facility Name

Local Institution - 401

City

Zurich

ZIP/Postal Code

Country

Switzerland

Facility Name

Local Institution - 427

City

Headington

ZIP/Postal Code

OX3 9DU

Country

United Kingdom

Facility Name

Local Institution - 428

City

London

ZIP/Postal Code

SE5 9RS

Country

United Kingdom

Facility Name

Local Institution - 430

City

Sutton (Surrey)

ZIP/Postal Code

SM2 5PT

Country

United Kingdom

12. IPD Sharing Statement

Citations:

PubMed Identifier

34672961

Citation

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.

Results Reference

derived

PubMed Identifier

33119479

Citation

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.

Results Reference

derived

Links:

URL

https://www.bms.com/researchers-and-partners/clinical-trials-and-research.html

Description

BMS Clinical Trial Information

URL

http://www.BMSStudyConnect.com

Description

BMS Clinical Trial Patient Recruiting

Learn more about this trial

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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

Leukemia, Myeloid, Acute

About this trial

Eligibility Criteria

Sites / Locations

Arms of the Study

Arm 1

Arm 2

Arm 3

Outcomes

Primary Outcome Measures

Secondary Outcome Measures

Full Information

1. Study Identification

2. Study Status

3. Sponsor/Collaborators

4. Oversight

5. Study Description

6. Conditions and Keywords

7. Study Design

8. Arms, Groups, and Interventions

10. Eligibility

12. IPD Sharing Statement

Learn more about this trial