Olutasidenib for the Treatment of Patients With IDH1 Mutated AML, MDS or CMML After Donor Hematopoietic Cell Transplant

NCT06543381 | Recruiting Phase 1 DMC FDA Drug

• 3 other identifiers: 23483NCI-2024-06471P30CA033572
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 2

Brief Summary

This phase I trial tests the safety, side effects, and effectiveness of olutasidenib in preventing the return of disease (relapse) in patients who have undergone donor (allogeneic) hematopoietic cell transplant for acute myeloid leukemia (AML), myelodysplastic syndrome (MDS), or chronic myelomonocytic leukemia (CMML) carrying an IDH1 mutation. Olutasidenib is in a class of medications called IDH1 inhibitors. It works by slowing or stopping the growth of cancer cells. Giving olutasidenib may be safe, tolerable and/or effective in preventing relapse in patients with IDH1 mutated AML, MDS or CMML after an allogeneic hematopoietic cell transplant.

Conditions

Myelodysplastic Syndrome; Acute Myeloid Leukemia; Chronic Myelomonocytic Leukemia

Outcome Measures

Primary Outcomes (2)

• Incidence of adverse events (AEs)

  AEs will be graded according to National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0.

  Up to 30 days after last dose of study treatment

• Proportion of patients completing at least 6 months of study therapy

  Tolerability will be defined as the proportion of patients who complete at least 6 months of study therapy.

  Up to 2 years

Secondary Outcomes (7)

• Overall survival (OS)

  From start of treatment to death, assessed up to 2 years

• Leukemia-free survival (LFS)

  From start of treatment to relapse or death, assessed up to 2 years

• Time to relapse

  From start of treatment to relapse, assessed up to 2 years

• Non-relapse mortality (NRM)

  From start of treatment to death from causes other than relapse, assessed up to 2 years

• Graft versus host disease (GVHD) free, relapse-free survival (GRFS)

  From start of treatment to grade III or IV acute GVHD, chronic GVHD requiring systemic therapy, relapse, or death, assessed up to 2 years

Study Arms (1)

Treatment (olutasidenib)

EXPERIMENTAL

Starting 50-120 days after transplant, patients receive olutasidenib PO BID on days 1-28 of each cycle. Cycles repeat every 28 days for up to 24 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo blood sample collection on study.

Procedure: Biospecimen Collection; Drug: Olutasidenib

Interventions

Biospecimen Collection PROCEDURE

Undergo blood sample collection

Also known as: Biological Sample Collection, Biospecimen Collected, Specimen Collection

Treatment (olutasidenib)

Olutasidenib DRUG

Given PO

Also known as: FT 2102, FT-2102, FT2102, IDH1-R132 Inhibitor FT-2102, Rezlidhia

Treatment (olutasidenib)

Eligibility Criteria

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

You may qualify if:

• Documented informed consent of the participant and/or legally authorized representative
• Agreement to allow the use of archival tissue from diagnostic tumor biopsies. If unavailable, exceptions may be granted with study principal investigator (PI) approval
• Age: ≥ 18 years
• Eastern Cooperative Oncology Group (ECOG) ≤ 2 or Karnofsky performance status (KPS) ≥ 70
• Patients who are scheduled to receive or have already undergone allogeneic hematopoietic cell transplantation (alloHCT) from any donor type, any conditioning regimen, and regardless of GVHD prophylaxis will be include
• Patients must have AML, MDS, or CMML with mIDH1 diagnosis at diagnosis (regardless of time from HCT). Note: Patient with pre-HCT disease relapse will no be included if mIDH1 is not detected after relapse
• Day 30 marrow post alloHCT should show evidence of morphologic remission with \< 5% bone marrow (BM) blasts. Patients with MRD-positive status either by flow cytometry or IDH1 mutation testing will be eligible
• Patients with previous therapy with IDH1 inhibitors will be included
• Absolute neutrophil count (ANC) \> 1000/mm\^3 (within 28 days prior to day 1 of protocol)
• Hemoglobin ≥ 8.0 gm/dL (within 28 days prior to day 1 of protocol)
• Platelets ≥ 50,000/mm\^3 (within 28 days prior to day 1 of protocol) Note: Patients with lower counts can enroll if infection cytomegalovirus (CMV)/human herpes virus 6 (HHV6), etc. is being treated actively
• Bilirubin ≤ 2 x upper limit of normal (ULN) (within 28 days prior to day 1 of protocol) (unless has Gilbert's disease). Patients with abnormal liver function tests (LFTs) due to active GVHD will not be eligible
• Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase \[SGOT\])/alanine aminotransferase (ALT) (serum glutamic pyruvic transaminase \[SGPT\]) ≤ 2 x ULN (within 28 days prior to day 1 of protocol). Patients with abnormal LFTs due to active GVHD will not be eligible
• Creatinine clearance of ≥ 30/min/1.73 m\^2 for participants with creatinine levels above institutional normal per 24 hour urine test or the Cockcroft-Gault formula (within 28 days prior to day 1 of protocol)
• Corrected QT interval (QTc) ≤ 480 ms (Note: To be performed within 28 days prior to day 1 of protocol therapy)

You may not qualify if:

• Patients with more than one allogeneic HCT
• History of allergic reactions attributed to compounds of similar chemical or biological composition to study agent
• Active diarrhea considered clinically significant and may impair oral drug administration
• Clinically significant uncontrolled illness
• Uncontrolled infection requiring systemic antimicrobials
• Active infection: Patients with treated viral, bacterial or fungal infections that are controlled on therapy will be allowed to participate
• Participant has detectable human immunodeficiency virus (HIV) viral load within the previous 6 months (must have viral load testing prior to study enrollment if participant has a known history of HIV 1/2 antibodies)
• Active hepatitis B or C, or HIV
• Females only: Pregnant or breastfeeding
• Active grade II-IV acute GVHD per Mount Sinai Acute Graft Versus Host Disease International Consortium (MAGIC) criteria and/or requiring systemic steroids with prednisone dose equivalent of ≥ 0.25 mg/kg at end of 4 weeks. Patients with a mild form of acute GVHD involving skin, gut or liver requiring topical steroid creams or oral beclomethasone (8 mg/day), entocort, (9 mg/day) and/or solumedrol (and equivalent prednisone) will be allowed
• Any other condition that would, in the investigator's judgment, contraindicate the patient's participation in the clinical study due to safety concerns with clinical study procedures
• Prospective participants who, in the opinion of the investigator, may not be able to comply with all study procedures (including compliance issues related to feasibility/logistics)

Sponsors & Collaborators

• City of Hope Medical Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (2)

City of Hope Medical Center

Duarte, California, 91010, United States

RECRUITING

Cleveland Clinic Cancer Center

Cleveland, Ohio, 44195, United States

NOT YET RECRUITING

MeSH Terms

Conditions

Leukemia, Myeloid, Acute; Leukemia, Myelomonocytic, Chronic; Myelodysplastic Syndromes

Interventions

Specimen Handling; olutasidenib

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Myelodysplastic-Myeloproliferative Diseases; Bone Marrow Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Investigative Techniques

Study Officials

• Amandeep Salhotra, MD

  City of Hope Medical Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Amandeep Salhotra, MD

CONTACT

1-626-359-8111; asalhotra@coh.org

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 5, 2024
• First Posted: August 9, 2024
• Study Start: January 17, 2025
• Primary Completion (Estimated): February 5, 2027
• Study Completion (Estimated): February 5, 2027
• Last Updated: March 5, 2026

Record last verified: 2026-03

Locations

US (2)