Using olutasidenib to prevent relapse in patients with IDH1 mutated blood cancers after transplant

Pilot Trial of Olutasidenib Maintenance Post Allogeneic Hematopoietic Cell Transplantation in Patients Carrying IDH1 Mutation With AML, MDS, or CMML Disease

This study is testing if a new drug called olutasidenib can help prevent blood cancers from coming back in patients with a specific gene mutation after they have had a stem cell transplant.

Quick facts

• Phase: Phase 1
• Study type: Interventional
• Enrollment: 15 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: City of Hope Medical Center (Academic / other)
• Drugs / interventions: prednisone
• Locations: 2 sites (Duarte, California and 1 other locations)
• Trial ID: NCT06543381 on ClinicalTrials.gov

What this trial studies

This phase I trial evaluates the safety and effectiveness of olutasidenib, an IDH1 inhibitor, in preventing disease relapse in patients with IDH1 mutated acute myeloid leukemia (AML), myelodysplastic syndrome (MDS), or chronic myelomonocytic leukemia (CMML) who have undergone donor hematopoietic cell transplantation. The study aims to assess overall survival and leukemia-free survival rates, as well as the incidence of relapse and non-relapse mortality. Participants will be monitored for immune reconstitution and disease status through various molecular and cytometric techniques.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 and older with IDH1 mutated AML, MDS, or CMML who have undergone allogeneic hematopoietic cell transplantation.

Not a fit: Patients without an IDH1 mutation or those who have not undergone allogeneic hematopoietic cell transplantation may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could significantly reduce the risk of relapse in patients with IDH1 mutated blood cancers after transplantation.

How similar studies have performed: Other studies have shown promise with IDH1 inhibitors in treating similar conditions, indicating a potential for success in this approach.

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)

Where this trial is running

Duarte, California and 1 other locations

• City of Hope Medical Center — Duarte, California, United States (Recruiting)
• Cleveland Clinic Cancer Center — Cleveland, Ohio, United States (Not_yet_recruiting)

Study contacts

• Principal investigator: Amandeep Salhotra, MD — City of Hope Medical Center
• Study coordinator: Amandeep Salhotra, MD

Conditions Acute Myeloid Leukemia; Chronic Myelomonocytic Leukemia; Myelodysplastic Syndrome