Evaluating olutasidenib for patients with specific blood disorders

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

This study is testing if a new drug called olutasidenib can help people with certain blood disorders feel better and improve their health.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 15 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: M.D. Anderson Cancer Center (Academic / other)
• Locations: 1 site (Houston, Texas)
• Trial ID: NCT06566742 on ClinicalTrials.gov

What this trial studies

This clinical trial aims to assess the effectiveness of olutasidenib in treating patients with IDH1-mutated clonal cytopenia of undetermined significance (CCUS), lower-risk myelodysplastic syndromes (MDS), and chronic myelomonocytic leukemia (CMML). The primary objective is to determine the response rate to olutasidenib monotherapy, while secondary objectives include evaluating transfusion independence, safety, survival rates, and the potential for leukemia transformation. Additionally, the study will explore gene expression and DNA methylation profiles to identify predictors of treatment response. Participants will receive olutasidenib and be monitored for various clinical outcomes.

Who should consider this trial

Good fit: Ideal candidates include adults aged 18 and older with pathologically proven CCUS or lower-risk MDS/CMML and a documented IDH1 mutation.

Not a fit: Patients without an IDH1 mutation or those with higher-risk MDS/CMML may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could provide a new therapeutic option for patients with IDH1-mutated blood disorders, potentially improving their quality of life and clinical outcomes.

How similar studies have performed: Other studies have shown promising results with similar targeted therapies in hematologic malignancies, suggesting potential for success in this approach.

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 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.

Where this trial is running

Houston, Texas

• MD Anderson Cancer Center — Houston, Texas, United States (Recruiting)

Study contacts

• Principal investigator: Kelly Chien, MD — M.D. Anderson Cancer Center
• Study coordinator: Kelly Chien, MD

Conditions Myelodysplastic Syndromes; Chronic Myelomonocytic Leukemia; Clonal Cytopenia of Undetermined Significance