Enasidenib for Patients With Clonal Cytopenia of Undetermined Significance and Mutations in IDH2A Decentralized Trial

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

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Clonal Cytopenia of Undetermined Significance; CCUS Clonal Cytopenia of Undetermined Significance
• Intervention / Treatment: Drug: Enasidenib

• Study Type: Interventional
• Enrollment (Estimated): 15
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Kelly Bolton, M.D., Ph.D.; Phone Number: 314-273-5711; Email: bolton@wustl.edu

Study Locations

• United States
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Washington University School of Medicine
      • Principal Investigator: Kelly Bolton, M.D., Ph.D.
      • Contact: Kelly Bolton, M.D. Ph.D.; Phone Number: 314-273-5711; Email: bolton@wustl.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• 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 × 109/L
  • Platelets <100 × 109/L
• IDH2 gene mutation (R140 or R172), performed locally, at a frequency ≥ 2%.
• At least 18 years of age.
• ECOG performance status 0-2

• Adequate organ function as defined below:

  • AST(SGOT)/ALT(SGPT) ≤ 3.0 x IULN
  • Serum total bilirubin < 1.5 x IULN (un upper limit of bilirubin 5 mg/dL is acceptable if it can be attributed to Gilbert's syndrome or erythropoiesis)
  • Creatinine clearance > 50 mL/min by Cockcroft-Gault glomerular filtration rate estimation or serum creatinine ≤ 2 x IULN
• The effects of enasidenib on the developing human fetus are unknown. For this reason, women of childbearing potential and men must agree to use adequate contraception prior to study entry, for the duration of study participation, and for 4 months after the last dose of enasidenib. Should a woman become pregnant or suspect she is pregnant while participating in this study, she must inform her treating physician immediately. Men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of the study, and for 4 months after the last dose of enasidenib.
• Ability to understand and willingness to sign an IRB approved written informed consent document (or that of legally authorized representative, if applicable).

Exclusion Criteria:

• Indication of hematologic disease by bone marrow biopsy within 6 months of study entry.

  • Evidence of disease progression from time of bone marrow biopsy to enrollment based on investigator review of symptoms and complete blood counts
• Active malignancy (defined as > 1 cm disease on most recent CT scan in the past 6 months).
• Currently receiving therapy for solid tumor malignancy or received within the last 6 months.
• Currently receiving any other investigational agents.
• Known dysphagia, short-gut syndrome, gastroparesis, or other conditions that limit the ingestion or gastrointestinal absorption of drugs administered orally.
• A history of allergic reactions attributed to compounds of similar chemical or biologic composition to enasidenib or other agents used in the study.
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, or cardiac arrhythmia.
• Pregnant and/or breastfeeding. Women of childbearing potential must have a negative pregnancy test within 72 hours of study entry.
• Positive direct Coombs test.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Enasidenib; Participants will receive enasidenib 100 mg daily for 18 cycles (each cycle is 28 days). 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.

Drug: Enasidenib; Provided by BMS.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Best hematologic response	Hematologic response to enasidenib will be evaluated according to a modified version of the IWG 2006 Criteria for Hematologic Improvement for patients with MDS on clinical trials	Up to 18 cycles (each cycle is 28 days) of treatment (up to approximately 17 months)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Toxicity as measured by the number of adverse events experienced by participant	Measured by CTCAE v 5.0	From start of treatment through 30 days after the last day of treatment (up to approximately 18 months)
Change in mutant IDH2 variant allele fraction	The IDH2 variant allele fraction reflects the clonal dominance in the blood. Blood samples will be drawn at various time points throughout the study to determine the IDH2 variant allele fraction. The lower the IDH2 variant allele fraction the better the outcome.	Baseline, day 1 of cycles 3/6/9/12/15 (each cycle is 28 days), and end of treatment (up to approximately 17 months)
Acute myeloid leukemia (AML-free) or myelodysplastic syndrome (MDS)-free survival		From start of treatment through completion of follow-up (up to approximately 18 months)

Collaborators and Investigators

• Sponsor: Washington University School of Medicine
• Collaborators: Bristol-Myers Squibb; Damon Runyon Cancer Research Foundation
• Investigators: Principal Investigator: Kelly Bolton, M.D., Ph.D., Washington University School of Medicine

Publications and helpful links

Helpful Links

• Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine

Study record dates

Study Major Dates

• Study Start (Estimated): April 30, 2024
• Primary Completion (Estimated): March 31, 2026
• Study Completion (Estimated): April 30, 2026

Study Registration Dates

• First Submitted: January 16, 2024
• First Submitted That Met QC Criteria: January 26, 2024
• First Posted (Estimated): February 5, 2024

Study Record Updates

• Last Update Posted (Estimated): February 5, 2024
• Last Update Submitted That Met QC Criteria: January 26, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Keywords: IDH2; Enasidenib; CCUS; Clonal Cytopenia of Undetermined Significance
• Additional Relevant MeSH Terms: Hematologic Diseases; Blood Platelet Disorders; Leukocyte Disorders; Anemia; Thrombocytopenia; Leukopenia
• Other Study ID Numbers: 24-x022

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Individual participant data that underlie the results reported in this article after deidentification (including text, tables, figures and appendices) will be available.
• IPD Sharing Time Frame: The data will be available immediately following publication with no end date.
• IPD Sharing Access Criteria: The data will be available immediately following publication with no end date. Access will be provided to anyone and for any purpose.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No