A Phase 2 Study Evaluating Olutasidenib in Patients With IDH1-mutated Clonal Cytopenia of Undetermined Significance and Lower-risk Myelodysplastic/Syndromes/Chronic Myelomonocytic Leukemia.

To learn if olutasidenib can help to control CCUS, MDS, and/or CMML. The safety of the drug will also be studied.

Study Overview

• Status: Recruiting
• Conditions: Myelodysplastic Syndromes; Chronic Myelomonocytic Leukemia; Clonal Cytopenia of Undetermined Significance
• Intervention / Treatment: Drug: Olutasidenib

Detailed Description

Primary Objectives - To determine the response rate of olutasidenib monotherapy in patients with IDH1-mutated CCUS or lower-risk MDS/CMML

Secondary Objectives

• To evaluate the rates of transfusion independence, defined as the absence of transfusions over a period of at least 8 weeks
• To ascertain the safety and tolerability of olutasidenib monotherapy in these participants populations
• To determine survival and rates of leukemia transformation
• To analyze reduction in IDH1 clone size

Exploratory Objectives

- To investigate global gene expression profiles, DNA methylation profiles, and other potential prognostic markers to explore predictors of antitumor activity and/or resistance to treatment.

OUTLINE:

Patients receive olutasidenib orally (PO) twice daily (BID) on days 1-28 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients with CCUS receive up to 18 months of olutasidenib. Patients with lower-risk MDS/CMML can receive olutasidenib until disease progression or unacceptable toxicity. Additionally, patients undergo blood sample collection and bone marrow aspiration and biopsy on study.

After completion of study treatment, patients are followed up every 3 months for up to 3 years.

• Study Type: Interventional
• Enrollment (Estimated): 15
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Kelly Chien, MD; Phone Number: (713) 745-7584; Email: kchien@mdanderson.org

Study Locations

• United States
  • Texas
    • Houston, Texas, United States, 77030
      • Recruiting
      • MD Anderson Cancer Center
      • Contact: Kelly Chien, MD; Phone Number: 713-745-7584; Email: Kchien@mdanderson.org
      • Principal Investigator: Kelly Chien, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

1. Pathologically proven CCUS or lower-risk MDS/CMML.

   1. CCUS is defined as the presence of cytopenia (absolute neutrophil count < 1.8 x 10^9/L, hemoglobin < 13 g/dL in males or < 12 g/dL in females, and/or platelets < 150 x 10^9/L) for at least 30 days that are otherwise unexplained and with no diagnostic hematopathologic features of myeloid neoplasms. Patients with known Duffy-null phenotype must have absolute neutrophil counts less than their lower limit of normal.
   2. Lower-risk MDS/CMML includes patients with International Prognostic Scoring System (IPSS) low- or intermediate-1-risk disease and Revised IPSS (IPSS-R) score ≤ 3.5 and Molecular IPSS (IPSS-M) very low-, low-, or moderate low-risk categories.
2. Patients must have a documented IDH1 mutation with variant allele frequency (VAF) ≥ 0.02.
3. Patients ≥ 18 years old.
4. Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2
5. Bilirubin ≤ 2 times upper limit of normal (ULN) or ≤ 3 times ULN in patients with Gilbert Syndrome.
6. Aspartate transaminase (AST), alanine transaminase (ALT), and alkaline phosphatase ≤ 3 times ULN.
7. Acceptable renal function with serum creatinine ≤ 1.5 times ULN or calculated creatinine clearance ≥ 50 mL/min (as assessed by Cockcroft-Gault, Modification of Diet in Renal Disease Formula [MDRD], or Chronic Kidney Disease Epidemiology [CKD-Epi] validated measures).
8. Negative serum or urine pregnancy test if female of childbearing potential.
9. 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. Appropriate highly effective method(s) of contraception include oral or injectable hormonal birth control, intrauterine device (IUD), and double barrier methods (for example a condom in combination with a spermicide).
10. Agreement for male patients not to donate sperm and for female patients of childbearing potential not to donate ova during the study and for 90 days after the final dose of study drug.
11. Ability and willingness to signed informed consent prior to beginning study and undergoing procedures.

Exclusion Criteria:

1. Patients unable to swallow oral medications, or patients with gastrointestinal conditions (e.g., malabsorption, resection, etc.) deemed by the Investigator to jeopardize intestinal absorption.
2. Patients with any concurrent uncontrolled clinically significant medical condition, including life-threatening severe infection or psychiatric illness, which could place the patient at unacceptable risk of study treatment.
3. Known active hepatitis B (hepatitis B virus [HBV]) or hepatitis C (hepatitis C virus [HCV]) or HIV infection.
4. Pregnant or nursing women or women of childbearing potential not using highly effective contraception; male patients not using highly effective contraception as defined in the inclusion criteria.

5. Subject with white blood cell count > 25 x10^9/L.

   • Note: hydroxyurea use is permitted to meet this criterion with no washout required.
6. Unwillingness or inability to comply with procedures either required in this protocol or considered standard of care.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Olutasidenib; 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.	Drug: Olutasidenib; Given by PO

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.

Collaborators and Investigators

• Sponsor: M.D. Anderson Cancer Center
• Collaborators: Rigel Pharmaceuticals
• Investigators: Principal Investigator: Kelly Chien, MD, M.D. Anderson Cancer Center

Publications and helpful links

Helpful Links

• MD Anderson Cancer Center

Study record dates

Study Major Dates

• Study Start (Actual): December 10, 2024
• Primary Completion (Estimated): August 31, 2027
• Study Completion (Estimated): August 31, 2029

Study Registration Dates

• First Submitted: August 20, 2024
• First Submitted That Met QC Criteria: August 20, 2024
• First Posted (Actual): August 22, 2024

Study Record Updates

• Last Update Posted (Actual): March 4, 2026
• Last Update Submitted That Met QC Criteria: March 2, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms; Chronic Disease; Disease Attributes; Neoplasms by Histologic Type; Hematologic Diseases; Leukemia, Myeloid; Myelodysplastic-Myeloproliferative Diseases; Bone Marrow Diseases; Leukemia; Pathological Conditions, Signs and Symptoms; Hemic and Lymphatic Diseases; Leukemia, Myelomonocytic, Chronic; Myelodysplastic Syndromes; olutasidenib
• Other Study ID Numbers: 2024-0509; NCI-2024-07045 (Other Identifier: NCI-CTRP Clinical Registry)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No