Enasidenib for Clonal Cytopenia

Recruiting at 1 trial location

Overseen By Kelly Bolton, M.D.

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Washington University School of Medicine

Must not be taking: Investigational agents

Disqualifiers: Active malignancy, Uncontrolled illness, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 1

Duration: 18 months

15 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests enasidenib, a drug that may help individuals with clonal cytopenia of undetermined significance (CCUS), a condition characterized by unexplained low blood cell counts. Researchers believe enasidenib might improve these counts by blocking a specific protein called IDH2. The trial aims to determine if enasidenib is safe and effective for treating CCUS. Individuals with low blood counts for at least six months and a specific IDH2 gene mutation might be suitable candidates for this trial. As a Phase 2 trial, this research focuses on measuring enasidenib's effectiveness in an initial, smaller group, offering participants a chance to contribute to important findings.

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.

Is there any evidence suggesting that enasidenib is likely to be safe for humans?

Research shows that enasidenib is generally safe and well-tolerated in people with certain blood cancers. Previous studies indicate it is safe for patients with IDH2-mutated myeloid malignancies, a type of blood cancer. The treatment did not cause major safety issues, and patients handled it well. The FDA noted that enasidenib did not require special safety measures, such as a Risk Evaluation and Mitigation Strategy (REMS), indicating no major safety concerns.

While enasidenib is approved for other uses, this trial aims to test its safety specifically for clonal cytopenia, a condition with low blood cell counts. Safety data from other conditions suggest enasidenib might be a safe option for this trial as well, but this study will help confirm that. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for clonal cytopenia?

Most treatments for clonal cytopenia focus on managing symptoms or controlling the progression of the disease, often using drugs that target specific mutations or involve supportive care like blood transfusions. Enasidenib stands out because it specifically targets the mutated IDH2 enzyme, which plays a role in certain blood disorders. By inhibiting this enzyme, enasidenib not only addresses the underlying cause but also has the potential to delay progression to more severe conditions like AML or MDS. Researchers are excited about enasidenib because it offers a more targeted approach, potentially reducing the need for more aggressive treatments and improving patient outcomes.

What evidence suggests that enasidenib might be an effective treatment for clonal cytopenia?

Earlier studies have shown that enasidenib holds promise for treating acute myeloid leukemia, a type of blood cancer, in patients with IDH2 mutations, achieving a response rate of 40.3%. Enasidenib blocks the mutated IDH2 protein, which plays a role in these blood conditions. In this trial, participants will receive enasidenib to evaluate its potential to improve blood cell counts in people with clonal cytopenia of undetermined significance (CCUS). Although specific data for CCUS is limited, the drug's success in similar conditions suggests it could be effective. Researchers aim to determine if these benefits apply to CCUS in this ongoing study. ^{1 6 7 8 9}

Who Is on the Research Team?

Giulia Petrone, M.D.

Principal Investigator

Washington University School of Medicine

Are You a Good Fit for This Trial?

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

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

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

My cancer has a specific IDH2 gene mutation.

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.

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• Enasidenib

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.

How Is the Trial Designed?

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.

Enasidenib is already approved in United States, European Union for the following indications:

Approved in United States as Idhifa for:

• Relapsed or refractory acute myeloid leukemia (AML) with an isocitrate dehydrogenase-2 (IDH2) mutation

Approved in European Union as Idhifa for:

• Acute myeloid leukaemia (AML) with an isocitrate dehydrogenase 2 (IDH2) mutation

Who Is Running the Clinical Trial?

Washington University School of Medicine

Lead Sponsor

Trials

2,027

Recruited

2,353,000+

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

Published Research Related to This Trial

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]

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]

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, 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 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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06240754

Study Details | NCT06240754 | Enasidenib for Patients ... The purpose of this study is to find out whether enasidenib is a safe and effective treatment for CCUS.

2. cancer.gov cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2021-12349

A Study of Enasidenib in Patients with Clonal Cytopenia ... This phase I trial studies the safety of enasidenib in improving blood counts in patients with clonal cytopenia of undetermined significance (CCUS) and an IDH2 ...

3. centerwatch.com centerwatch.com/clinical-trials/listings/NCT05102370/a-study-of-enasidenib-in-people-with-clonal-cytopenia-of-undetermined-significance

A Study of Enasidenib in People With Clonal Cytopenia ... Study researchers think that a drug called enasidenib may help people with clonal cytopenia of undetermined significance (CCUS) because the drug blocks the ...

4. withpower.com withpower.com/trial/phase-1-anemia-9-2021-d90a3

Enasidenib for Clonal Cytopenia · Info for Participants Enasidenib has shown effectiveness in treating acute myeloid leukemia (a type of blood cancer) with IDH2 mutations, with a response rate of 40.3% in patients ...

5. ashpublications.org ashpublications.org/thehematologist/article/doi/10.1182/hem.V21.4.2024414/516780/Targeting-the-Natural-History-of-Clonal

Targeting the Natural History of Clonal Hematopoiesis This small pilot study is open at several sites and designed to assess enasidenib in patients with clonal cytopenia of undetermined significance (CCUS) who ...

6. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/nda/2017/209606Orig1s000RiskR.pdf

209606Orig1s000 - accessdata.fda.gov The Agency informed the Applicant that based on the currently available data, there were no safety issues that require a REMS for enasidenib.

7. ashpublications.org ashpublications.org/blood/article/130/6/722/36814/Enasidenib-in-mutant-IDH2-relapsed-or-refractory

Enasidenib in mutant IDH2 relapsed or refractory acute ... Enasidenib, a selective inhibitor of mutant IDH2 enzymes, was safe and well tolerated in patients with IDH2-mutated myeloid malignancies. Enasidenib induced ...

8. mds-hub.com mds-hub.com/medical-information/safety-and-efficacy-of-enasidenib-in-idh2-mutated-myelodysplastic-syndrome

Safety and efficacy of enasidenib in IDH2-mutated ... This study demonstrated encouraging response rates in patients with IDH2-mutated MDS and requires further observation in a larger study ...

9. ctv.veeva.com ctv.veeva.com/study/a-study-of-enasidenib-in-people-with-clonal-cytopenia-of-undetermined-significance

A Study of Enasidenib in People With Clonal Cytopenia of ... The purpose of this study is to find out whether enasidenib is a safe and effective treatment for CCUS.