Enasidenib for Clonal Cytopenia

Recruiting in Palo Alto (17 mi)

Overseen by Kelly Bolton, M.D.

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

Sponsor: Washington University School of Medicine

Must not be taking: Investigational agents

Disqualifiers: Active malignancy, Uncontrolled illness, others

No Placebo Group

Prior Safety Data

Approved in 2 Jurisdictions

Trial Summary

What is the purpose of this 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.

Do I need to stop my current medications to join the trial?

The trial information does not specify if you need to stop taking your current medications. However, you cannot participate if you are currently receiving therapy for a solid tumor malignancy or any other investigational agents.

What data supports the effectiveness of the drug Enasidenib for Clonal Cytopenia?

Enasidenib has shown effectiveness in treating acute myeloid leukemia (AML) with IDH2 mutations, where it helps cancer cells mature into normal blood cells. In trials, it improved conditions in a significant number of patients with AML, suggesting potential benefits for other blood-related conditions like Clonal Cytopenia. ^{1 2 3 4 5}

What makes the drug Enasidenib unique for treating clonal cytopenia?

Enasidenib is unique because it is an oral drug that specifically targets and inhibits mutant IDH2 proteins, which are involved in certain blood disorders and cancers. This targeted approach is different from traditional chemotherapy, as it directly addresses the genetic mutation causing the disease. ^{2 4 5 6 7}

Research Team

Kelly Bolton, M.D.

Principal Investigator

Washington University School of Medicine

Eligibility Criteria

This trial is for individuals with clonal cytopenia of undetermined significance (CCUS), which includes conditions like anemia, low white blood cell count, and low platelet count. Participants should have mutations in the IDH2 gene.

Inclusion Criteria

I am 18 years old or older.

Agreement to use adequate contraception for women of childbearing potential and men

I have had unexplained low blood counts for at least 6 months.

Exclusion Criteria

I am not currently on any experimental drugs.

I do not have any unmanaged ongoing illnesses.

I am currently undergoing treatment for cancer or have within the last 6 months.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive enasidenib 100 mg daily for 18 cycles, each cycle lasting 28 days

18 months

Visits at baseline, day 1 of cycles 3/6/9/12/15, and end of treatment

Follow-up

Participants are monitored for safety and effectiveness after treatment, including assessment of adverse events

1 month

Treatment Details

Interventions

• Enasidenib (IDH2 Inhibitor)

Trial Overview The study is testing enasidenib, a drug that targets the mutated IDH2 protein. The goal is to see if it can safely and effectively improve blood cell counts in people with CCUS.

Participant Groups

Group I: Enasidenib Experimental Treatment 1 Intervention

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.

Who Is Running the Clinical Trial?

Washington University School of Medicine

Lead Sponsor

Trials

2,027

Recruited

2,353,000+

David H. Perlmutter

Washington University School of Medicine

Chief Executive Officer since 2015

MD from Washington University School of Medicine

Paul Scheel

Washington University School of Medicine

Chief Medical Officer since 2022

MD from Washington University School of Medicine

Damon Runyon Cancer Research Foundation

Collaborator

Trials

10

Recruited

1,100+

Bristol-Myers Squibb

Industry Sponsor

Trials

2,731

Recruited

4,127,000+

Headquarters

New York City, USA

Known For

Oncology & Cardiovascular

Top Products

Eliquis, Opdivo, Revlimid, Orencia

Christopher Boerner

Bristol-Myers Squibb

Chief Executive Officer since 2023

PhD in Business Administration from the Haas School of Business, University of California, Berkeley; BA in Economics and History from Washington University in St. Louis

Deepak L. Bhatt

Bristol-Myers Squibb

Chief Medical Officer since 2024

MD from Yale University; MSc in Clinical Epidemiology from the University of Pennsylvania

Findings from Research

Enasidenib, a selective inhibitor for mutant IDH2, showed a 40.3% overall response rate in patients with relapsed/refractory acute myeloid leukemia (AML) carrying IDH2 mutations, indicating its efficacy as a treatment option.

The study found that while enasidenib effectively suppressed the oncogenic metabolite 2-hydroxyglutarate (2-HG), this suppression alone did not predict patient response, suggesting that differentiation of hematopoietic cells is the primary mechanism of action for the drug.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Enasidenib induces acute myeloid leukemia cell differentiation to promote clinical response. Amatangelo, MD., Quek, L., Shih, A., et al.[2022]

Enasidenib is a targeted treatment for relapsed or refractory acute myeloid leukemia that effectively inhibits mutant IDH2 proteins, as shown in a Phase I/II study assessing its safety and efficacy in patients with IDH2 mutations.

The study revealed that enasidenib significantly induces CYP3A enzyme activity, which is important to consider when prescribing other medications that are metabolized by this pathway, due to the potential for drug interactions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Modeling and simulation of the endogenous CYP3A induction marker 4β-hydroxycholesterol during enasidenib treatment. Li, Y., Connarn, JN., Chen, J., et al.[2022]

Enasidenib is an effective oral treatment for acute myeloid leukemia (AML) that specifically targets IDH2 mutations, showing clinical improvement in 19.6% of patients and laboratory improvement in 38.8% of cases based on clinical trials.

While enasidenib is generally well-tolerated, it can cause differentiation syndrome, a serious side effect that requires careful monitoring by healthcare providers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An evaluation of enasidenib for the treatment of acute myeloid leukemia. Del Principe, MI., Paterno, G., Palmieri, R., et al.[2019]

Enasidenib, an IDH2 inhibitor, was found to be generally well tolerated and effective in inducing responses in 53% of patients with IDH2-mutated myelodysplastic syndromes, even in those previously treated with hypomethylating agents.

The study involved 17 patients with a median follow-up of 11 months, showing a median overall survival of 16.9 months and a median event-free survival of 11 months, highlighting the potential of enasidenib as a treatment option for this patient group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Enasidenib in patients with mutant IDH2 myelodysplastic syndromes: a phase 1 subgroup analysis of the multicentre, AG221-C-001 trial. Stein, EM., Fathi, AT., DiNardo, CD., et al.[2022]

In a clinical trial involving 107 patients with newly diagnosed mutant-IDH2 acute myeloid leukaemia, the combination of enasidenib and azacitidine significantly improved overall response rates, with 74% of patients responding compared to 36% in the azacitidine-only group.

The combination treatment was well tolerated, with no treatment-related deaths reported, although some patients experienced common grade 3 or 4 adverse events like thrombocytopenia and neutropenia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Enasidenib plus azacitidine versus azacitidine alone in patients with newly diagnosed, mutant-IDH2 acute myeloid leukaemia (AG221-AML-005): a single-arm, phase 1b and randomised, phase 2 trial. DiNardo, CD., Schuh, AC., Stein, EM., et al.[2022]

Enasidenib (Idhifa®) is an oral medication that specifically inhibits the IDH2 enzyme and has been approved in the USA for treating adults with relapsed or refractory acute myeloid leukaemia (AML) with an IDH2 mutation.

The approval of enasidenib marks a significant milestone as it is the first global treatment option specifically targeting IDH2 mutations in AML, highlighting its potential efficacy in this specific patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Enasidenib: First Global Approval. Kim, ES.[2022]

Enasidenib is an effective oral treatment for relapsed/refractory acute myeloid leukemia (AML) with IDH2 mutations, showing durable complete remissions in about 20% of patients and leading to improved survival in preclinical models.

The drug works by normalizing levels of the oncometabolite (R)-2-hydroxyglutarate, promoting differentiation of leukemic cells, and is generally well tolerated, although it can cause differentiation syndrome as a notable side effect.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Enasidenib. Krämer, A., Bochtler, T.[2019]

References

1. United States pubmed.ncbi.nlm.nih.gov

Enasidenib induces acute myeloid leukemia cell differentiation to promote clinical response. [2022]

2. New Zealand pubmed.ncbi.nlm.nih.gov

Modeling and simulation of the endogenous CYP3A induction marker 4β-hydroxycholesterol during enasidenib treatment. [2022]

3. England pubmed.ncbi.nlm.nih.gov

An evaluation of enasidenib for the treatment of acute myeloid leukemia. [2019]

4. England pubmed.ncbi.nlm.nih.gov

Enasidenib in patients with mutant IDH2 myelodysplastic syndromes: a phase 1 subgroup analysis of the multicentre, AG221-C-001 trial. [2022]

5. England pubmed.ncbi.nlm.nih.gov

Enasidenib plus azacitidine versus azacitidine alone in patients with newly diagnosed, mutant-IDH2 acute myeloid leukaemia (AG221-AML-005): a single-arm, phase 1b and randomised, phase 2 trial. [2022]

6. New Zealand pubmed.ncbi.nlm.nih.gov

Enasidenib: First Global Approval. [2022]

7. Germany pubmed.ncbi.nlm.nih.gov

Enasidenib. [2019]