A Study of Enasidenib in People With Clonal Cytopenia of Undetermined Significance

Study Overview
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Brief Summary
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Study researchers think that a drug called enasidenib may help people with clonal cytopenia of undetermined significance (CCUS) because the drug blocks the mutated IDH2 protein, which may improve blood cell counts. The purpose of this study is to find out whether enasidenib is a safe and effective treatment for CCUS.

Official Title
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A Pilot Study of Enasidenib for Patients With Clonal Cytopenia of Undetermined Significance and Mutations in IDH2

Conditions
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Clonal Cytopenia of Undetermined Significance, CCUS Clonal Cytopenia of Undetermined Significance

Intervention / Treatment
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* Drug: Enasidenib


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≥18 years at the time of signing the informed consent form. Willing and able to adhere to the study visit schedule and other protocol requirements. Unexplained cytopenia for at least 6 months. Cytopenia is defined as the presence of ≥1 blood count indexes below the following thresholds: Hgb <10 g/dL ANC <1.8 × 10^9/L Platelets <100 × 10^9/L Results of bone marrow biopsy within 1 month of study entry (screening bone marrow biopsy) must not indicate hematologic disease. IDH2 gene mutation (R140 or R172), performed locally, at a frequency >2%. ECOG performance status of 0-2. Adequate organ function, defined as: Serum aspartate aminotransferase/serum glutamic oxaloacetic transaminase (AST/SGOT) and alanine aminotransferase (ALT/SGPT) ≤3x upper limit of normal (ULN), unless the subject has Gilbert's syndrome. Serum total bilirubin <1.5x ULN. Higher levels are acceptable if these can be attributed to ineffective erythropoiesis. In these cases, approval from the study Principal Investigator is required. Creatinine clearance greater than 50 mL/min based on the Cockroft-Gault glomerular filtration rate estimation. Patients being enrolled on study on the basis of anemia, will only be eligible if folate, B12, serum iron, serum ferritin, total iron binding capacity, haptoglobin and peripheral smear within normal limits Women of childbearing potential may participate provided they have a negative serum pregnancy test at screening and a negative serum or urine pregnancy test within 72 h of starting treatment. Women of childbearing potential (WOCBP) and males with partners who are WOCBP must agree to abstain from sexual intercourse or to use 1 highly effective form of contraception during the study and for at least 4 months following the last dose of enasidenib. Males with partners who are WOCBP must agree to use a barrier method. Exclusion Criteria: Active malignancy defined as >1-cm disease on most recent CT scan in the past 6 months or recent history of cancer (i.e. within the past 5 years) with >50% chance of cancer recurrence in the next 5 years. Current or prior history of hematologic malignancy. Therapy (including maintenance therapy) for solid-tumor malignancy within the last 6 months. Known dysphagia, short-gut syndrome, gastroparesis, or other conditions that limit the ingestion or gastrointestinal absorption of drugs administered orally. Active uncontrolled systemic fungal, bacterial, or viral infection (defined as ongoing signs/symptoms related to the infection without improvement despite appropriate antibiotics, antiviral therapy, and/or other treatment). Positive direct Coombs test Evidence of hypersplenism on physical exam Pregnant or lactating (women).

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Participants with CCUS with mutations in IDH2<br>Participants will have CCUS with mutations in IDH2 | Drug: Enasidenib<br>* Study participants will receive enasidenib 100 mg daily for 18 months. Participants will continue treatment with enasidenib until confirmed progression to AML or MDS, development of unacceptable toxicity, or suspicion of disease progression, provided the patient is deriving clinical benefit, which will be determined at the discretion of the principal investigator.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Best Response | The primary objective is to estimate the rate of hematologic improvement. The endpoint is evaluated as the best response at any point in up to 18 months of treatment with enasidenib. | Up to 18 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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CCUS, Clonal Cytopenia of Undetermined Significance, Enasidenib, 21-268, Memorial Sloan Kettering Cancer Center