Olutasidenib Combined With Co-targeted Therapy in Relapsed or Refractory IDH1-mutated Myeloid Malignancies Harboring Activated Signaling Pathway Mutations

NCT07032727 | Recruiting Phase 2 DMC FDA Drug

• 2 other identifiers: 2025-0520NCI-2025-04331
• Study Type: interventional
• Target: 68
• Locations: 1 country
• Sites: 1

Brief Summary

To learn about the safety and tolerability of study drug combinations in patients with relapsed/refractory, IDH1-mutated myeloid malignancies with a co-signaling mutation.

Conditions

IDH1-Mutated Malignancies; Mutations; Targeted Therapy

Outcome Measures

Primary Outcomes (1)

• Safety and adverse events (AEs)

  Incidence of Adverse Events, Graded According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version (v) 5.0

  Through study completion; an average of 1 year

Study Arms (5)

Arm 1A Safety Lead-In/Expansion:

EXPERIMENTAL

Treatment with Olutasidenib + Cladribine + Cytarabine

Drug: Olutasidenib; Drug: Cladribine (CLAD); Drug: Cytarabine

Arm 1B Expansion

EXPERIMENTAL

Treatment with Olutasidenib + Cladribine + Cytarabine + Venetoclax

Drug: Olutasidenib; Drug: Cladribine (CLAD); Drug: Venetoclax; Drug: Cytarabine

Arm 2A Safety Lead-In/Expansion

EXPERIMENTAL

Treatment with Olutasidenib + Gilteritnib

Drug: Olutasidenib; Drug: Gilteritinib

Arm 2B Expansion

EXPERIMENTAL

Treatment with Olutasidenib + Gilteritnib + Venetoclax

Drug: Olutasidenib; Drug: Venetoclax; Drug: Gilteritinib

Arm 3A Safety Lead-In/Expansion:

EXPERIMENTAL

Treatment with Olutasidenib + Ruxolitinib

Drug: Olutasidenib; Drug: Ruxolitinib

Interventions

Cytarabine DRUG

Given SQ

Arm 1A Safety Lead-In/Expansion:; Arm 1B Expansion

Olutasidenib DRUG

Given by po

Arm 1A Safety Lead-In/Expansion:; Arm 1B Expansion; Arm 2A Safety Lead-In/Expansion; Arm 2B Expansion; Arm 3A Safety Lead-In/Expansion:

Cladribine (CLAD) DRUG

Given by IV

Arm 1A Safety Lead-In/Expansion:; Arm 1B Expansion

Venetoclax DRUG

Given by po

Arm 1B Expansion; Arm 2B Expansion

Gilteritinib DRUG

Given by po

Arm 2A Safety Lead-In/Expansion; Arm 2B Expansion

Ruxolitinib DRUG

Given by po

Arm 3A Safety Lead-In/Expansion:

Eligibility Criteria

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

You may qualify if:

• Age ≥ 18 years.
• Participants with a diagnosis of relapsed and/or refractory AML (including biphenotypic or bilineage leukemia including a myeloid component) OR high-risk MDS, MPN, or MDS/MPN (defined as ≥10% blasts on peripheral flow cytometry or bone marrow biopsy).
• Participants must have a documented IDH1 mutation.
• Participants must also have a documented co-signaling mutation in one or more of the following: KRAS, NRAS, PTPN11, CBL, NF1, FLT3-ITD, FLT3-TKD, KIT, JAK2, MPL, CALR, CSF3R.
• Eastern Cooperative Oncology Group (ECOG) Performance Status ≤2.
• Adequate renal function with estimated GFR ≥ 30 by the 2021 Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI).
• Adequate hepatic function, defined as direct bilirubin ≤ 2x upper limit of normal (ULN) and AST and ALT ≤ 3x ULN unless the increase is due to Gilbert's disease or leukemic involvement, in which case direct bilirubin, AST, and ALT ≤ 5x ULN will be considered eligible.
• The interval from prior treatment to time of initiation will be at least 14 days OR five half-lives for both cytotoxic and non-cytotoxic (e.g. immunotherapy agent(s)). Oral hydroxyurea and/or cytarabine (up to 2g/m2) is allowed for participants with rapidly proliferative disease prior tothe start and during the first two cycles of therapy, for clinical benefit and after discussion with the PI. Continuation of concurrent intrathecal therapy for controlled CNS disease is permitted.
• Ability to understand and the willingness to sign an informed consent document.

You may not qualify if:

• Participants who have received prior olutasidenib (Rezlidhiai, previously FT-2102).
• Participants with translocation t(15;17) or acute promyelocytic leukemia (French-American British (FAB) class M3-AML).
• Participants with any concurrent uncontrolled clinically significant medical condition, including life threatening infection, which could place the patient at unacceptable risk of study treatment.
• Participants with any uncontrolled psychiatric illness that would limit compliance with study requirements.
• Participants with a New York Heart Association (NYHA) Functional Classification of III or IV.
• Participants with active graft-versus-host-disease (GVHD) status post stem cell transplant (Participants without active GVHD on phototherapy for chronic skin GVHD are permitted after discussion with the PI). Participants must have discontinued calcineurin inhibitors at least 4 weeks prior to the start of study treatment.
• Participants with active, uncontrolled CNS leukemia.
• Participants with any severe gastrointestinal or metabolic condition which could interfere with the absorption of oral study medications.
• Known active hepatitis B (HBV), hepatitis C (HCV), or human immunodeficiency virus (HIV) infection. For participants with evidence of chronic HBV or HIV infection, the HBV or HIV viral load must be undetectable, respectively. For participants with a history of HCV, it must be treated and cured with an undetectable HCV viral load.
• Participant has white blood cell count \>25 x 109/L (Note: Hydroxyurea and cytarabine are permitted to mean this criterion).
• The effects of the study drug on the developing human fetus or transmission through breast feeding are unknown. Therefore, nursing women and women with a positive urine pregnancy test and excluded. Additionally, women of child-bearing potential (WOCBP) and men who are sexually active with WOCBP who are not willing to maintain adequate contraception are excluded.
• ii. History of hysterectomy or bilateral salpingo-oophorectomy. iii. Ovarian failure (Follicle Stimulating Hormone and Estradiol in menopausal range, who have received Whole Pelvic Radiation Therapy).
• iv. History of bilateral tubal ligation or another surgical sterilization procedure.
• b. Approved methods of birth control are as follows: hormonal contraception (i.e. birth control pills, injection, transdermal patch, vaginal ring, hormonal implant), intrauterine device (IUD), tubal ligation or hysterectomy, subject/partner post-vasectomy, double barrier methods (e.g. condom in combination with spermicide). Abstinence for the duration of the trial and drug washout period is an acceptable practice; however periodic abstinence, the rhythm method, and the withdrawal method are not acceptable methods of birth control. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform the treating physician immediately.
• c. Adequate contraception must be maintained from initiation of the study drug until 90 days after the last dose of the study drug.

Sponsors & Collaborators

• Rigel Pharmaceuticals: collaborator
• M.D. Anderson Cancer Center: lead

Study Sites (1)

MD Anderson Cancer Center

Houston, Texas, 77030, United States

RECRUITING

Related Links

• MD Anderson Cancer Center

MeSH Terms

Interventions

olutasidenib; Cladribine; venetoclax; gilteritinib; ruxolitinib; Cytarabine

Intervention Hierarchy (Ancestors)

2-Chloroadenosine; Adenosine; Purine Nucleosides; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Deoxyadenosines; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Arabinonucleosides

Study Officials

• Courtney DiNardo, MD

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Courtney DiNardo, MD

CONTACT

713-794-1141; cdinardo@mdanderson.org

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 16, 2025
• First Posted: June 24, 2025
• Study Start: September 12, 2025
• Primary Completion (Estimated): June 1, 2027
• Study Completion (Estimated): June 1, 2029
• Last Updated: April 15, 2026

Record last verified: 2026-04

Locations

US (1)