NCT05401097

IDH Targeted/Non- Targeted vs Non-targeted/IDH-targeted Approaches in the Treatment of Newly Diagnosed IDH Mutated AML Patients Not Candidates for Intensive Induction Therapy (I- DATA Study)

Randomized, Sequential, Open-Label Study to Evaluate the Efficacy of IDH Targeted/Non- Targeted Versus Non-targeted/IDH-targeted Approaches in the Treatment of Newly Diagnosed IDH Mutated AML Patients Not Candidates for Intensive Induction Therapy (I- DATA Study)

• Status: Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 125 (estimated)
• Sponsor: Alice Mims · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This phase II study compares the order of treatment with ivosidenib or enasidenib and azacitidine plus venetoclax in treating older patients with acute myeloid leukemia with genetic changes in the IDH1 or IDH2 genes (IDH mutated). Ivosidenib is in a class of medications called isocitrate dehydrogenase-1 (IDH1) inhibitors. It works by slowing or stopping the growth of cancer cells. Enasidenib is in a class of medications called an IDH2 inhibitor. It also works by slowing or stopping the growth of cancer cells. Venetoclax is in a class of medications called B-cell lymphoma-2 (BCL-2) inhibitors. It may stop the growth of cancer cells by blocking Bcl-2, a protein needed for cancer cell survival. Azacitidine is in a class of medications called demethylation agents. It works by helping the bone marrow to produce normal blood cells and by killing abnormal cells. This study may help researchers determine which treatment order is best for older patients with IDH mutated acute myeloid leukemia: 1) ivosidenib or enasidenib followed by azacitidine plus venetoclax; or 2) azacitidine plus venetoclax followed by ivosidenib or enasidenib.

Detailed description

PRIMARY OBJECTIVE: I. To compare overall treatment failure at 24 months in newly diagnosed IDH1 or IDH2 mutated AML patients ≥18 years who are not candidates for intensive induction chemotherapy randomized to either sequential treatment with an IDH inhibitor in combination with azacitidine followed by venetoclax in combination with azacitidine (Arm A) or sequential treatment with venetoclax in combination with azacitidine followed by an IDH inhibitor in combination with azacitidine (Arm B). SECONDARY OBJECTIVES: I. To compare overall survival at 24 months between patients treated on the two sequential treatment arms. II. To compare time to overall treatment failure and time-to-event overall survival between patients treated on the two sequential treatment arms. III. To determine the degree of response and compare complete remission (CR) rates, CR/complete remission with hematologic improvement (CRh)/complete remission with incomplete blood count recovery (CRi) rates, and overall response rates (CR/CRh/CRi/morphologic leukemia free state \[MLFS\]) for first-line therapy and second-line therapy between patients treated on the two sequential treatment arms. IV. To compare the duration of response (CR/CRh/CRi) to first-line therapy and second-line therapy between patients treated on the two sequential treatment arms. V. To determine toxicity profiles for patients treated on the two sequential treatment arms, overall and by first-line treatment and by second-line treatment. VI. To determine causes that would not allow patients that first line treatment fails to go on to second line treatment. VII. To determine the number and proportion of patients who are able to go onto allogeneic transplantation in both treatment arms. EXPLORATORY OBJECTIVES: I. To assess the clonal, biochemical and differentiation changes in AML cells during IDH-inhibitor and venetoclax treatment using flow cytometry and serial next generation sequencing on bone marrow specimens before and during treatment to assess for potential resistance mutations or clonal evolution that may be predictors of relapse. II. To examine molecular properties of AML cells associated with primary and secondary resistance to each treatment arm to determine if particular subtypes of AML may be more or less likely to respond to a certain treatment modality. III. To perform minimal residual disease (MRD) monitoring via liquid biopsy via our custom-designed 30-gene mutation ArcherPlex panel to monitor clonal dynamics during both sequential treatment arms. IV. To determine the feasibility of longitudinal sociodemographic and social determinants of health (SDOH) data collection for adults with AML on a clinical trial. V. To determine the acceptability of longitudinal sociodemographic/SDOH data collection for adults with AML on a clinical trial. VI. To describe changes in SDOH for adults with AML on a clinical trial. VII. To describe associations between SDOH measures and trial outcomes for adults with AML on a clinical trial. OUTLINE: Patients are randomized into 1 of 2 arms. ARM A: For IDH1 mutated AML patients randomized to first-line therapy with IDHi+aza, patients will receive Ivosidenib 500mg po orally daily on Days 1-28 of each 28 day cycle. For IDH2 mutated AML patients randomized to first-line therapy with IDHi+aza, patients will receive Enasidenib 100mg po orally daily on Days 1-28 of each 28 day cycle. Azacitidine will be given to both groups intravenously or subcutaneously at 75mg/m2 daily on days 1-7 or 1-5/8-9 of each 28 day cycle. Subsequent cycles after CR/CRi/CRh/MLFS achievement may be adjusted in timing and dosing. ARM B: For both IDH1 and IDH2 mutated AML patient randomized to first-line therapy with Ven+aza, patients will receive venetoclax dosing with the ramp-up and dosing per the FDA-label (based off of concurrent drug interactions). Azacitidine will be given intravenously at 75mg/m2 daily on days 1-7 of each 28-day cycle. Subsequent cycles after CR/CRi/CRh/MLFS achievement may be adjusted in timing and dosing. After completion of the study treatment, patients are followed up at 30 days and then every 3 months for 5 years from registration, until death, or withdrawal of consent from study assessments and all further follow-up.

Conditions

• Acute Myeloid Leukemia

Interventions

Type	Name	Description
DRUG	Azacitidine	Given IV or SC
PROCEDURE	Biopsy	Undergo biopsy of the bone marrow
DRUG	Enasidenib	Given PO
DRUG	Ivosidenib	Given PO
DRUG	Venetoclax	Given PO

Timeline

• Start date: 2022-09-13
• Primary completion: 2027-09-30
• Completion: 2029-06-30
• First posted: 2022-06-02
• Last updated: 2025-05-14

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study