A Phase 2 Study Evaluating Olutasidenib in Combination With Hypomethylating Agents in Patients With IDH1-mutated Higher-risk Myelodysplastic Syndromes, Chronic Myelomonocytic Leukemia, or Advanced Myeloproliferative Neoplasm

NCT06597734 | Recruiting Phase 2 DMC FDA Drug

• 2 other identifiers: 2024-0515NCI-2024-07758
• Study Type: interventional
• Target: 45
• Locations: 1 country
• Sites: 1

Brief Summary

To learn if olutasidenib, when combined with a drug called a hypomethylating agent (HMA) can help to control MDS, CMML, and/or MPN. The safety of the drug combination will also be studied.

Conditions

Chronic Myelomonocytic Leukemia; Advanced Myeloproliferative Neoplasms; IDH1-mutated Higher-Risk Myelodysplastic Syndromes

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 (1)

Olutasidenib+Azacitidine-IV or SubQ

EXPERIMENTAL

Participants will take capsules of olutasidenib 2 times each day while you are on study. Each dose should be taken about 12 hours apart at least 1 hour before or 2 hours after a meal. Azacitidine IV or Sub Q for 7 days every 28 days.

Drug: Olutasidenib

Interventions

Olutasidenib DRUG

Given by PO

Olutasidenib+Azacitidine-IV or SubQ

Eligibility Criteria

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

You may qualify if:

• Pathologically proven higher-risk MDS/CMML or advanced MPN
• MDS participants must have International Prognostic Scoring System (IPSS) intermediate-2- or high-risk disease or Revised IPSS (IPSS-R) score \>= 3.5 or Molecular IPSS (IPSS-M) moderate high-, high-, or very high-risk disease or bone marrow blast percentage.
• CMML patients must have CPSS-Mol int-1, int-2, or high-ris disease (Elena C et al, Blood 2016)
• Advanced MPN is defined as bone marrow blast percentage \>=/=10%.
• Participants on the treatment-naive arm must not have received a prior HMA. Agents such as growth factors (e.g. erythropoietin stimulating agents, luspatercept, eltrombopag, granulocyte colony stimulating factors), cyclosporine, and/or hydroxyurea are allowed.
• Patients on the previously-treated arm must have received a prior HMA and/or ivosidenib. Prior stem cell transplantation in allowed\>
• Participants must have a documented IDH1 mutation
• Patients with previously-treated MDS must be ineligible to receive treatment with ivosidenib or have progressed on treatment with ivosidenib.
• Participants \>=/= 18 years old
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2 (Appendix A)
• Acceptable liver function
• Bilirubin \</= 2 times upper limit of normal (ULN) or \<;/= 3 times ULN in participants with Gilbert Syndrome
• Aspartate transaminase (AST), alanine transaminase (ALT), and alkaline phosphatase \</= 3 times ULN
• Acceptable renal function calculated creatinine clearance \>/= 50 mL/min (as assessed by Cockcroft-Gault, MDRD, or CKD-Epi validated measures)
• Negative serum or urine pregnancy test if female of childbearing potential c. For fertile men and women, agreement to use highly effective contraceptive methods for the duration of study participation and 90 days after the last dose of study medication d. Agreement for male participants not to donate sperm and for female participants of childbearing potential not to donate ova during the study and for 90 days after the final dose of study drug

You may not qualify if:

• Participants unable to swallow oral medications, or participants with gastrointestinal conditions (e.g., malabsorption, resection, etc.) deemed by the Investigator to jeopardize intestinal absorption
• Participants with any concurrent uncontrolled clinically significant medical condition, including life-threatening severe infection or psychiatric illness, which could place the participant at unacceptable risk of study treatment
• Patients must have discontinued prior chemotherapy at least 1 week prior to the start of study treatment. Patients with MPN must be off JAK inhibitors at the start of study treatment
• Patients with active graft-versus-host-disease (GVHD) status post stem cell transplantation, including active chronic GVHD requiring topical therapy. Patients must have discontinued calcineurin inhibitors at least 4 weeks prior to the start of study treatment
• Known active hepatitis B (HBV) or hepatitis C (HCV) or HIV infection
• Pregnant or nursing women or women of childbearing potential not using highly effective contraception; male participants not using highly effective contraception
• Participants with white blood cell count \&gt; 25 x109/L Note: hydroxyurea use is permitted to meet this criterion
• Unwillingness or inability to comply with procedures either required in this protocol or considered standard of care

Sponsors & Collaborators

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

Study Sites (1)

MD Anderson Cancer Center

Houston, Texas, 77030, United States

RECRUITING

Related Links

• MD Anderson Cancer Center

MeSH Terms

Conditions

Leukemia, Myelomonocytic, Chronic

Interventions

olutasidenib

Condition Hierarchy (Ancestors)

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

Study Officials

• Kelly Chien, MD

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Kelly Chien, MD

CONTACT

713-745-7584; Kchien@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: September 12, 2024
• First Posted: September 19, 2024
• Study Start: January 28, 2025
• Primary Completion (Estimated): August 31, 2027
• Study Completion (Estimated): August 31, 2029
• Last Updated: April 15, 2026

Record last verified: 2026-04

Locations

US (1)