Olutasidenib, Venetoclax, and Azacitidine in IDH1 Mutated Newly Diagnosed Acute Myeloid Leukemia Patients Eligible for Intensive Induction Chemotherapy

NCT06782542 | Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: 20240763
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is as follows:

1. 1.Determine whether people receiving the combination treatment of olutasidenib, venetoclax, and azacitidine have the same, more, or fewer side effects compared to the usual chemotherapy treatment that people with this condition receive.
2. 2.Determine how well the combination treatment of olutasidenib, venetoclax, and azacitidine works compared to the usual chemotherapy treatment that people with this condition receive.

Conditions

Acute Myeloid Leukemia; IDH1 Mutation

Outcome Measures

Primary Outcomes (2)

• Number of Participants Experiencing Excessive Toxicity

  The number of participants experiencing excessive toxicity in six (6) patient safety lead-in over the duration of study treatment will be reported. All treatment-emergent adverse events (TEAEs) will be graded using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.

  Up to 12 months

• Composite Complete Remission (CRc)

  Composite complete remission (CRc) among participants will be reported as a percentage. CRc is includes number of participants experiencing complete remission \[CR\], complete remission with partial hematologic recovery \[CRh\] or complete remission with incomplete hematologic recovery \[CRi\] after up to 3 cycles as defined by modified 2022 European LeukemiaNet (ELN) criteria.

  Up to 3 months

Secondary Outcomes (20)

• Number of Participants Experiencing Unacceptable Toxicity

  Up to 13 months

• Number of Participants Experiencing Treatment-Emergent Adverse Events

  Up to 13 months

• Number of Participants Experiencing Serious Adverse Events

  Up to 13 months

• Number of Participants Experiencing Adverse events of special interest (AESIs)

  Up to 13 months

• Number of participants who died within 30-days

  Up to 30 days

Study Arms (1)

OLUVENAZA Treatment Group

EXPERIMENTAL

Participants in this group will receive combination treatment of Olutasidenib, Venetoclax and Azacitidine orally for up to 12 cycles, each cycle lasting 28 days. Total participation duration is about 14 months

Drug: Olutasidenib; Drug: Venetoclax; Drug: Azacitidine

Interventions

Olutasidenib DRUG

Olutasidenib will be supplied as 150 mg capsules to be administered orally, twice per day (BID) on an empty stomach (fasting at least 1 hour before or 2 hours after a meal), starting on Cycle 1 Day 1, and will be given continuously.

OLUVENAZA Treatment Group

Venetoclax DRUG

Participants will receive Venetoclax as a 100mg tablet to be self-administered orally with a meal and water once daily, two hours after starting Olutasidenib administration, starting on Cycle 1 Day 1. The dosing regimen of Venetoclax is as follows: * Cycle 1: Days 1 - 21 over a 28-day cycle * Cycle 1 Week 1: Ramp-up dosing schedule up to 400mg (4 x 100mg/tablet) * For participants with blast clearance: Cycle 2 and beyond: Days 1 - 14 over a 28-day cycle * For participants with persistent clearance: Cycle 2 through 4: Days 1 - 21

OLUVENAZA Treatment Group

Azacitidine DRUG

Participants will receive Azacitidine 75 mg/m2 per day via subcutaneous (SC) injection or intravenous (IV) infusion on Days 1-7 of each cycle.

OLUVENAZA Treatment Group

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Participant is an adult male or female participant aged 18-75 years considered eligible to undergo intensive induction chemotherapy at the time of signing the informed consent form (ICF).
• Eastern Cooperative Oncology Group (ECOG) performance status ≤2
• Confirmed diagnosis of:
• Newly diagnosed AML Isocitrate dehydrogenase 1 (IDH1) R132 mutated disease as assessed locally. Note: historical results from within 30 days of informed consent will be accepted if the participant did not receive systemic treatment after collection.
• Secondary AML, including prior hypomethylating agents (HMA) exposure for myelodysplastic syndrome (MDS), myeloproliferative neoplasms (MPN), or MDS/MPN is allowed.
• Participant must have adequate organ function, defined by the following:
• Aspartate transaminase (AST) and alanine aminotransferase (ALT) values ≤3 × upper limit of normal (ULN) or ≤5 × ULN for participants with leukemic involvement.
• Bilirubin ≤2 ULN (≤3 × ULN in participants with Gilbert Syndrome) or ≤3 × ULN for participants with leukemic involvement.
• Creatinine clearance ≥30 mL/min (using Cockcroft-Gault), or serum creatinine ≤1.5 × ULN.
• The interval from prior treatment for an antecedent hematologic disorder to the first dose of study treatment (C1D1) will be at least 7 days for cytotoxic or non-cytotoxic (immunotherapy) agents. In addition, the following will be allowed:
• Intrathecal chemotherapy for prophylactic use or for controlled central nervous system (CNS) leukemia.
• Use of hydroxyurea for participants with rapidly proliferative disease is allowed before the start of study therapy and for the first 4 weeks on study treatment.
• Recovery from non-hematologic toxic effects of prior treatment to Grade ≤1, or baseline value according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 classification (excluding infertility, alopecia, or Grade 1 neuropathy).
• Baseline QT interval corrected using the Fridericia equation (QTcF) ≤ 480 msec. Note: This criterion does not apply to participants with a bundle branch block (BBB); for participants with BBB, a cardiology consult is recommended to ensure that QTcF is not prolonged.
• Female participants who are women of childbearing potential (WOCBP) must have a negative serum or urine (beta-human chorionic gonadotropin (βhCG)) pregnancy test at screening and negative serum or urine test documented within the 24-hour period prior to the first dose of study drug. WOCBP are defined as sexually mature women without prior hysterectomy or who have had any evidence of menses in the past 12 months. However, women who have been amenorrheic for 12 or more months are still considered to be of childbearing potential if the amenorrhea is possibly due to prior chemotherapy, anti-estrogens, or ovarian suppression (Section 4.8.1).

You may not qualify if:

• Relapsed/Refractory AML.
• ELN (2022) favorable risk AML, except for nucleophosmin 1 (NPM1) mutated AML, which is allowed.
• Acute promyelocytic leukemia (APL).
• Positive Fms related receptor tyrosine kinase 3-Internal tandem duplication (FLT3-ITD) mutation.
• Active CNS involvement by leukemia (other extramedullary disease is allowed).
• Participants \<18 years or \>75 years of age.
• Female participant who is pregnant or breastfeeding.
• Participant plans to become pregnant or father a child (including ova or sperm donation) while enrolled in this study or within 3 months after last dose of study treatment (Section 4.8).
• Participant has a known allergy or history of hypersensitivity to study drugs or their excipients.
• Previous therapy with olutasidenib (or ivosidenib or other IDH1 inhibitor) or venetoclax (or another B cell lymphoma 2 (BCL-2) inhibitor).
• Participant has active evidence of clinically significant unstable medical condition such as uncontrolled infection, severe metabolic abnormality, poorly controlled psychiatric illness, or symptomatic coronary artery disease (other than stable angina), which could place the participant at unacceptable risk of study treatment, per the Investigator's judgement.
• Participants receiving treatment with strong Cytochrome P450, family 3, subfamily A (CYP3A) inhibitors within 7 to 14 days or 5 half-lives (whichever is longer) prior to the first dose of study medication. Azoles are allowed with appropriate venetoclax dose reductions. Please note that participants receiving these medications would qualify for this study after undergoing a washout period of 7 to 14 days or 5 half-lives, whatever is longer for the inhibitor/inducer.
• Participants receiving treatment with strong CYP3A inducers within 7 to 14 days or 5 half-lives (whichever is longer) prior to the first dose of study medication. Please note that participants receiving these medications would qualify for this study after undergoing a washout period of 7 to 14 days or 5 half-lives, whatever is longer for the inhibitor/inducer.
• History of allogeneic hematopoietic stem cell transplant (HSCT) for a diagnosis other than AML if there is clinically significant active graft-versus-host disease (GVHD) or ongoing immunosuppressive therapy is required beyond prednisone 10 mg daily or equivalent. Otherwise, prior allogeneic HSCT is allowed.
• Participants with a concurrent active malignancy under treatment.

Sponsors & Collaborators

• Justin Watts, MD: lead
• Rigel Pharmaceuticals: collaborator

Study Sites (1)

University of Miami

Miami, Florida, 33136, United States

RECRUITING

MeSH Terms

Conditions

Leukemia, Myeloid, Acute

Interventions

olutasidenib; venetoclax; Azacitidine

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

Study Officials

• Justin Watts, MD

  University of Miami

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Justin Watts, MD

CONTACT

(305) 2438986; jxw401@miami.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Associate Professor of Clinical

Study Record Dates

• First Submitted: January 15, 2025
• First Posted: January 20, 2025
• Study Start: March 31, 2026
• Primary Completion (Estimated): March 31, 2029
• Study Completion (Estimated): March 31, 2029
• Last Updated: April 16, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)