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

Phase 2

Recruiting

• Conditions: Myelodysplastic Syndromes; Chronic Myelomonocytic Leukemia; Clonal Cytopenia of Undetermined Significance
• Interventions: Drug: Olutasidenib

• Registration Number: NCT06566742
• Lead Sponsor: M.D. Anderson Cancer Center

Brief Summary

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

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.

Study Timeline

• Study First Submitted: 2024-08-20
• Study First Submitted QC: 2024-08-20
• Study First Posted: 2024-08-22
• Study Start: 2024-12-10
• Status Verified: 2025-03
• Last Update Submitted: 2025-03-26
• Last Update Posted: 2025-04-01
• Primary Completion: 2027-08-31
• Study Completion: 2029-08-31

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 15

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 109/L, hemoglobin < 13 g/dL in males or < 12 g/dL in females, and/or platelets < 150 x 109/L) for at least 30 days that are otherwise unexplained and with no diagnostic hematopathologic features of myeloid neoplasms.
   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. Participants must have a documented IDH1 mutation with VAF ≥ 0.02

3. Participants ≥ 18 years old

4. Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2 (Appendix A)

5. Acceptable liver function

   1. Bilirubin ≤ 2 times upper limit of normal (ULN) or ≤ 3 times ULN in participants with Gilbert Syndrome
   2. Aspartate transaminase (AST), alanine transaminase (ALT), and alkaline phosphatase ≤ 3 times ULN

6. Acceptable renal function with serum creatinine ≤ 1.5 times ULN or calculated creatinine clearance ≥ 50 mL/min (as assessed by Cockcroft-Gault, MDRD, or CKD-Epi validated measures)

7. Negative serum or urine pregnancy test if female of childbearing potential

8. 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)

9. Agreement for male patients 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

10. Ability and willingness to signed informed consent prior to beginning study and undergoing procedures

Exclusion Criteria

1. Participants unable to swallow oral medications, or patients with gastrointestinal conditions (e.g., malabsorption, resection, etc.) deemed by the Investigator to jeopardize intestinal absorption
2. Participants 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 (HBV) or hepatitis C (HCV) or HIV infection
4. Pregnant or nursing women or women of childbearing potential not using highly effective contraception; male participants not using highly effective contraception as defined in the inclusion criteria
5. Participant with white blood cell count > 25 x109/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 & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Olutasidenib	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.

Primary Outcome Measures

Name	Time	Method
Safety and adverse events (AEs)	Through study completion; an average of 1 year.	Incidence of Adverse Events, Graded According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version (v) 5.0

Trial Locations

Locations (2)

MD Anderson Cancer Center; 🇺🇸 Houston, Texas, United States

MD Anderson Cancer Center; 🇺🇸 Houston, Texas, United States