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

Sponsor

Memorial Sloan Kettering Cancer Center (Other)

Overall Status

Recruiting

CT.gov ID

NCT05102370

Collaborator

(none)

Enrollment

Locations

Arm

Anticipated Duration (Months)

1.3

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

Brief 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.

Condition or Disease	Intervention/Treatment	Phase
Clonal Cytopenia of Undetermined Significance CCUS Clonal Cytopenia of Undetermined Significance	Drug: Enasidenib	Phase 1

Study Design

Study Type:

Interventional

Anticipated Enrollment :

15 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Oct 6, 2021

Anticipated Primary Completion Date :

Oct 6, 2023

Anticipated Study Completion Date :

Oct 6, 2023

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Participants with CCUS with mutations in IDH2 Participants will have CCUS with mutations in IDH2	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.

Arm

Intervention/Treatment

Experimental: Participants with CCUS with mutations in IDH2

Participants will have CCUS with mutations in IDH2

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.

Outcome Measures

Primary Outcome Measures

Best Response [Up to 18 months]
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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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).

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Mayo Clinic (Data Collection Only)	Rochester	Minnesota	United States	55905
2	Washington University (Data Collection and Specimen Analysis)	Saint Louis	Missouri	United States	63110
3	Memorial Sloan Kettering at Basking Ridge (All Protocol Activities)	Basking Ridge	New Jersey	United States	07920
4	Memoral Sloan Kettering Monmouth (All protocol activities)	Middletown	New Jersey	United States	07748
5	Memorial Sloan Kettering Bergen (Limited protocol activities)	Montvale	New Jersey	United States	07645
6	Memorial Sloan Kettering Suffolk-Commack (Limited protocol activities)	Commack	New York	United States	11725
7	Memorial Sloan Kettering Westchester (All Protocol Activities)	Harrison	New York	United States	10604
8	Memorial Sloan Kettering Cancer Center (All Protocol Activities)	New York	New York	United States	10065
9	Memorial Sloan Kettering Nassau (Limited protocol activities)	Rockville Centre	New York	United States	11553
10	Cleveland Clinic (Data Collection Only)	Cleveland	Ohio	United States	44195
11	Ohio State University (Data Collection Only)	Columbus	Ohio	United States	43210
12	Oregon Health & Science University (Data Collection Only)	Portland	Oregon	United States	97239