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

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

NCT ID: NCT06566742

Condition: Myelodysplastic Syndromes
Chronic Myelomonocytic Leukemia
Clonal Cytopenia of Undetermined Significance

Conditions: Official terms:
Leukemia
Leukemia, Myelomonocytic, Acute
Leukemia, Myelomonocytic, Chronic
Leukemia, Myelomonocytic, Juvenile
Myelodysplastic Syndromes
Cytopenia
Syndrome

Study type: Interventional

Study phase: Phase 2

Overall status: Not yet recruiting

Study design:

Allocation: N/A

Intervention model: Single Group Assignment

Primary purpose: Treatment

Masking: None (Open Label)

Intervention:

Intervention type: Drug
Intervention name: Olutasidenib
Description: Given by PO
Arm group label: Olutasidenib

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.

Criteria for eligibility:
Criteria:
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

Gender: All

Minimum age: 18 Years

Maximum age: N/A

Healthy volunteers: Accepts Healthy Volunteers

Locations:

Facility:
Name: MD Anderson Cancer Center

Address:
City: Houston
Zip: 77030
Country: United States

Contact:
Last name: Kelly Chien, MD

Phone: 713-745-7584
Email: kchien@mdanderson.org

Investigator:
Last name: Kelly Chien, MD
Email: Principal Investigator

Start date: February 28, 2025

Completion date: August 31, 2029

Lead sponsor:
Agency: M.D. Anderson Cancer Center
Agency class: Other

Collaborator:
Agency: Rigel Pharmaceuticals
Agency class: Industry

Source: M.D. Anderson Cancer Center

Record processing date: ClinicalTrials.gov processed this data on November 12, 2024

Source: ClinicalTrials.gov page: https://clinicaltrials.gov/ct2/show/NCT06566742
http://www.mdanderson.org