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

Clonal Cytopenia of Undetermined Significance Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05102370
• Other study ID #: 21-268
• Status: Recruiting
• Phase: Phase 1
• Start date: October 6, 2021
• Est. completion date: October 6, 2025

Study information

• Verified date: December 2023
• Source: Memorial Sloan Kettering Cancer Center
• Contact: Eytan Stein, MD
• Phone: 646-608-3749
• Email: SteinE[@]mskcc.org
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 15
• Est. completion date: October 6, 2025
• Est. primary completion date: October 6, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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).

Related Conditions & MeSH terms

• Anemia
• Clonal Cytopenia of Undetermined Significance
• Leukopenia
• Thrombocytopenia

Intervention

Drug:
• Enasidenib
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.

Locations

Country	Name	City	State
United States	Memorial Sloan Kettering at Basking Ridge (All Protocol Activities)	Basking Ridge	New Jersey
United States	Cleveland Clinic (Data Collection Only)	Cleveland	Ohio
United States	Ohio State University (Data Collection Only)	Columbus	Ohio
United States	Memorial Sloan Kettering Suffolk-Commack (Limited protocol activities)	Commack	New York
United States	Memorial Sloan Kettering Westchester (All Protocol Activities)	Harrison	New York
United States	Memorial Sloan Kettering Monmouth (All protocol activities)	Middletown	New Jersey
United States	Memorial Sloan Kettering Bergen (Limited protocol activities)	Montvale	New Jersey
United States	Memorial Sloan Kettering Cancer Center (All Protocol Activities)	New York	New York
United States	Oregon Health & Science University (Data Collection Only)	Portland	Oregon
United States	Mayo Clinic (Data Collection Only)	Rochester	Minnesota
United States	Memorial Sloan Kettering Nassau (Limited protocol activities)	Rockville Centre	New York
United States	Washington University (Data Collection and Specimen Analysis)	Saint Louis	Missouri

Sponsors (1)

Lead Sponsor	Collaborator
Memorial Sloan Kettering Cancer Center

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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

External Links

•   Memorial Sloan Kettering Cancer Center