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

NCT ID: NCT06543381

Last Updated: 2025-02-06

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE1
• Total Enrollment: 15 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-01-17
• Study Completion Date: 2027-02-05

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.

Detailed Description

PRIMARY OBJECTIVE:

I. Evaluate the safety and tolerability of olutasidenib as maintenance therapy after allogeneic hematopoietic cell transplantation (HCT) in patients with IDH1-mutated acute myeloid leukemia (AML), myelodysplastic syndrome (MDS), or chronic myelomonocytic leukemia (CMML).

SECONDARY OBJECTIVES:

I. Assess overall survival (OS) and leukemia-free survival (LFS) at 1 and 2 years after first dose of olutasidenib.

II. Estimate cumulative incidence of relapse (CIR), non-relapse mortality (NRM), graft-versus-host disease (GVHD) free, relapse-free survival (GRFS) at 1 and 2 years after first dose of olutasidenib.

III. Rate and grading of acute GVHD of grades 2-4 and 3-4 at day 100 post allogeneic HCT.

IV. Incidence and grading of chronic GVHD of all grades at 1 and 2 years after first dose of olutasidenib.

EXPLORATORY OBJECTIVES:

I. Monitor disease status by multiparameter flow cytometry among a subset of patients with minimal residual disease (MRD)+ disease when starting olutasidenib.

II. Molecular monitoring of disease status by HopeSeq complete (at City of Hope [COH]) and equivalent next generation sequencing (NGS) assay at Cleveland Clinic.

III. Monitor immune reconstitution by flow cytometry during protocol therapy. IV. Mutant (m)IDH1 testing on peripheral blood samples with standard polymerase chain reaction (PCR).

V. Investigate IFN-ɣ signaling in immune cell subsets before and during maintenance therapy.

VI. Monitor mIDH1 variant allele fraction (VAF) by droplet digital PCR (ddPCR) beads, emulsion, amplification, magnetics (BEAM)ing technology on peripheral blood.

OUTLINE:

Starting 50-120 days after bone marrow transplant, patients receive olutasidenib orally (PO) twice daily (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.

After completion of study treatment, patients are followed up at 30 days and then up to 2 years.

Conditions

Acute Myeloid Leukemia; Chronic Myelomonocytic Leukemia; Myelodysplastic Syndrome

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Treatment (olutasidenib)

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.

Group Type: EXPERIMENTAL

Biospecimen Collection

Intervention Type: PROCEDURE

Undergo blood sample collection

Olutasidenib

Intervention Type: DRUG

Given PO

Interventions

Biospecimen Collection

Undergo blood sample collection

Intervention Type: PROCEDURE

Olutasidenib

Given PO

Intervention Type: DRUG

Other Intervention Names

Biological Sample Collection; Biospecimen Collected; Specimen Collection; FT 2102; FT-2102; FT2102; IDH1-R132 Inhibitor FT-2102; Rezlidhia

Eligibility Criteria

Inclusion Criteria

• 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)
• Seronegative for HIV antigen/antibody (Ag/Ab) combo, hepatitis C virus (HCV) (if positive, hepatitis C ribonucleic acid [RNA] quantitation must be performed), active hepatitis B virus (HBV) (surface antigen negative), and syphilis (rapid plasma reagin [RPR]) (within 28 days prior to day 1 of protocol)
• Women of childbearing potential (WOCBP): negative urine or serum pregnancy test (within 28 days prior to day 1 of protocol). If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required
• Agreement by females and males of childbearing potential, defined as not being surgically sterilized (men and women) or have not been free from menses for > 1 year (women only), to use an effective method of birth control or abstain from heterosexual activity for the course of the study through at least 3 months after the last dose of protocol therapy

Exclusion Criteria

• 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
• Other active malignancy. Participants with history of prior malignancy treated with curative intent who achieved CR more than 2 years before study entry are eligible. This exclusion rule does not apply to non-melanoma skin tumors and in-situ cervical cancer
• 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)

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

City of Hope Medical Center

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Amandeep Salhotra, MD

Role: PRINCIPAL_INVESTIGATOR

City of Hope Medical Center

Locations

City of Hope Medical Center

Duarte, California, United States

Site Status: RECRUITING

Cleveland Clinic Cancer Center

Cleveland, Ohio, United States

Site Status: NOT_YET_RECRUITING

Countries

United States

Central Contacts

Amandeep Salhotra, MD

Role: CONTACT

asalhotra@coh.org

1-626-359-8111

Facility Contacts

Amandeep Salhotra

Role: primary

asalhotra@coh.org

626-218-2405

Abhay Singh, MD, MPH

Role: primary

singha21@ccf.org

866-320-4573

Other Identifiers

23483

Identifier Type: -

Identifier Source: org_study_id

NCI-2024-06471

Identifier Type: REGISTRY

Identifier Source: secondary_id

23483

Identifier Type: OTHER

Identifier Source: secondary_id

P30CA033572

Identifier Type: NIH

Identifier Source: secondary_id

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