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)

NCT05401097 | Recruiting Phase 2 DMC FDA Drug

• 3 other identifiers: OSU-21330NCI-2022-01324R01CA262496
• Study Type: interventional
• Target: 125
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Acute Myeloid Leukemia

Outcome Measures

Primary Outcomes (1)

• Overall treatment failure

  Defined as: 1) second occurrence of any of disease progression, relapse, failure to achieve complete remission (CR)/complete remission with hematologic improvement (CRh)/complete remission with incomplete blood count recovery (CRi), or 2) death from any cause. Within each treatment sequence, overall treatment failure rate will be defined as the number of patients with events divided by the number of eligible patients randomized. Patients who go to transplant will be considered a treatment success for a particular treatment sequence. All randomized patients meeting the eligibility criteria will be evaluable for treatment failure status by intention to treat. Will be analyzed using a Cochran-Mantel-Haenszel test, testing for a difference in proportions and stratifying on isocitrate dehydrogenase (IDH) mutation status.

  At 12 months from date of randomization

Secondary Outcomes (3)

• Difference in treatment failure rates between the two arms

  Up to 2 years

• Overall survival (OS)

  Up to 5 years

• Duration of response

  Up to 5 years

Study Arms (2)

Arm A (IDHi+Aza followed by Ven+aza)

EXPERIMENTAL

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.

Drug: Azacitidine; Procedure: Biopsy; Drug: Enasidenib; Drug: Ivosidenib; Drug: Venetoclax

Arm B (Ven+aza followed by IDHi+aza)

EXPERIMENTAL

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.

Drug: Azacitidine; Procedure: Biopsy; Drug: Enasidenib; Drug: Ivosidenib; Drug: Venetoclax

Interventions

Azacitidine DRUG

Given IV or SC

Also known as: 5 AZC, 5-AC, 5-Azacytidine, 5-AZC, Azacytidine, Azacytidine, 5-, Ladakamycin, Mylosar, Onureg, U-18496, Vidaza

Arm A (IDHi+Aza followed by Ven+aza); Arm B (Ven+aza followed by IDHi+aza)

Biopsy PROCEDURE

Undergo biopsy of the bone marrow

Also known as: BIOPSY_TYPE, Bx

Arm A (IDHi+Aza followed by Ven+aza); Arm B (Ven+aza followed by IDHi+aza)

Enasidenib DRUG

Given PO

Also known as: AG-221, CC-90007 Free Base

Arm A (IDHi+Aza followed by Ven+aza); Arm B (Ven+aza followed by IDHi+aza)

Ivosidenib DRUG

Given PO

Also known as: AG-120, Tibsovo

Arm A (IDHi+Aza followed by Ven+aza); Arm B (Ven+aza followed by IDHi+aza)

Venetoclax DRUG

Given PO

Also known as: ABT-0199, ABT-199, ABT199, GDC-0199, RG7601, Venclexta, Venclyxto

Arm A (IDHi+Aza followed by Ven+aza); Arm B (Ven+aza followed by IDHi+aza)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients with newly diagnosed IDH1 or IDH2 mutated AML
• Not a candidate for or refuses intensive induction therapy
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-2
• Creatinine clearance \> 40 ml/min
• Aspartate aminotransferase (AST)/ alanine aminotransferase (ALT) \< 5 x upper limit of normal
• Total bilirubin \< 1.5 x upper limit of normal (except for patients with Gilbert's disease)
• At the time of Venetoclax initiation, white blood cells (WBC) needs to be \< 25 × 103 microliter: Hydroxyurea can be used to achieve that level.
• For female patients of childbearing potential, willingness to abstain from heterosexual intercourse or use a protocol-recommended method of contraception from the screening visit throughout the study treatment period and for 30 days following the last dose of either study drug. A serum pregnancy test will be done at screening. A serum or urine pregnancy test will be done on Day 1 of each cycle for women of childbearing potential. If the urine pregnancy test is positive, a serum pregnancy test must be performed per institutional standards.
• The following methods are acceptable methods of contraception for the purpose of this study:
• Highly Effective Contraception Methods that can achieve a failure rate of less than 1% per year when used consistently and correctly are considered as highly effective birth control methods (Clinical Trials Facilitation Group 2014):
• Combined (estrogen and progestin containing) hormonal contraception associated with inhibition of ovulation (oral, intravaginal, transdermal).
• Progestin-only hormonal contraception associated with inhibition of ovulation (oral, injectable, implantable).
• Intrauterine device.
• Intrauterine hormone-releasing system.
• Bilateral tubal occlusion.

You may not qualify if:

• Patients with acute promyelocytic leukemia
• Known active central nervous system involvement of leukemia
• History of active non-myeloid malignancy except for the following: adequately treated local basal cell carcinoma or squamous cell carcinoma of the skin, cervical carcinoma in situ, superficial bladder cancer, asymptomatic prostate cancer without known metastatic disease. patients receiving tamoxifen/Aromatase Inhibitors for non-metastatic breast cancer, or any other cancer that has been in complete remission without treatment for \>= 5 years prior to enrollment
• Evidence of ongoing uncontrolled systemic bacterial, fungal or viral infection at the time of start of study treatment
• Uncontrolled infection with hepatitis C, hepatitis B, or human immunodeficiency virus (HIV)
• Pregnancy or breast feeding
• Concurrent participation in an investigational drug trial with therapeutic intent defined as prior study therapy within 14 days prior to study treatment
• Inability to tolerate oral medications including symptomatic disease significantly affecting gastrointestinal function such as inflammatory bowel disease or resection of stomach or small bowel

Sponsors & Collaborators

• Alice Mims: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

Ohio State University Comprehensive Cancer Center

Columbus, Ohio, 43210, United States

RECRUITING

Related Links

• The Jamesline

MeSH Terms

Conditions

Leukemia, Myeloid, Acute

Interventions

Azacitidine; Biopsy; enasidenib; ivosidenib; venetoclax

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

Aza Compounds; Organic Chemicals; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides; Cytodiagnosis; Cytological Techniques; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Specimen Handling; Diagnostic Techniques, Surgical; Surgical Procedures, Operative; Investigative Techniques

Study Officials

• Alice S Mims, MD

  Ohio State University Comprehensive Cancer Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

The Ohio State University Comprehensive Cancer Center

CONTACT

800-293-5066; OSUCCCClinicaltrials@osumc.edu

Molly Brandenburg

CONTACT

614-685-9573; molly.brandenburg@osumc.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: May 16, 2022
• First Posted: June 2, 2022
• Study Start: September 13, 2022
• Primary Completion (Estimated): September 30, 2027
• Study Completion (Estimated): June 30, 2029
• Last Updated: May 14, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)