Enasidenib for Clonal Cytopenia

Not currently recruiting at 13 trial locations

Overseen By Eytan Stein, MD

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Memorial Sloan Kettering Cancer Center

Disqualifiers: Active malignancy, Hematologic malignancy, Infection, others

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

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

Compensation: Varies

Number of Visits: Unknown

Duration: 18 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether a drug called enasidenib (also known as Idhifa) can help people with clonal cytopenia of undetermined significance (CCUS), a condition characterized by low blood cell counts for unknown reasons. Researchers believe enasidenib might block a mutated protein in the blood, potentially improving blood cell counts. The trial seeks participants who have experienced unexplained low blood counts for at least six months and have a specific gene mutation (IDH2). As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this potentially groundbreaking treatment.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the study team or your doctor.

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

Research has shown that enasidenib has been tested for safety in people with conditions like clonal cytopenia. In earlier studies, patients taking enasidenib experienced some side effects, usually mild, such as nausea and tiredness. More serious side effects occurred less frequently.

Since this trial is in an early stage, researchers are closely monitoring the treatment's safety. However, the FDA has already approved enasidenib for treating other blood disorders, indicating a known safety record in humans. This can offer some reassurance about its overall safety for those considering joining the trial. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Enasidenib is unique because it specifically targets mutations in the IDH2 gene, which are involved in clonal cytopenia. Unlike standard treatments that may not directly address these genetic mutations, enasidenib acts by inhibiting the abnormal enzyme activity caused by the IDH2 mutations, potentially rectifying the blood cell production issues. Researchers are excited about enasidenib because it offers a targeted approach, potentially leading to more effective and personalized treatment options for patients with clonal cytopenia linked to these specific genetic changes.

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

Research suggests that enasidenib, which participants in this trial will receive, may benefit individuals with clonal cytopenia of undetermined significance (CCUS) by targeting a specific genetic change. This drug blocks the altered IDH2 protein, potentially improving blood cell levels. Although direct clinical data for CCUS is limited, enasidenib has shown promise in other conditions with the same IDH2 mutation, supporting its potential effectiveness. Early studies indicated that patients with similar blood issues improved when treated with enasidenib. Therefore, enasidenib is expected to help people with CCUS by addressing the root cause of their low blood cell levels. ^{1 2 3 4 6}

Who Is on the Research Team?

Eytan Stein, MD

Principal Investigator

Memorial Sloan Kettering Cancer Center

Are You a Good Fit for This Trial?

Adults over 18 with clonal cytopenia of undetermined significance (CCUS) and IDH2 gene mutation can join this trial. They must have had unexplained low blood counts for at least 6 months, be in fair health, and able to follow the study plan. Pregnant women or those with active cancer, recent malignancy history, certain infections or conditions affecting drug absorption cannot participate.

Inclusion Criteria

I am able to get out of my bed or chair and move around.

Women of childbearing potential must have negative pregnancy tests and agree to contraception measures

My liver, kidneys, and blood iron levels are functioning well.

Exclusion Criteria

My spleen is overactive.

I have recently been treated for a solid tumor cancer.

I have a stomach or intestine condition that affects how medicines work in my body.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive enasidenib to evaluate its safety and effectiveness for up to 18 months

18 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Enasidenib

Trial Overview The trial is testing Enasidenib's safety and effectiveness on CCUS by blocking a mutated protein that may improve blood cell counts. Participants will take Enasidenib orally to see if it helps increase their white blood cells, platelets, and hemoglobin levels.

How Is the Trial Designed?

Group I: Participants with CCUS with mutations in IDH2 Experimental Treatment 1 Intervention

Participants will have CCUS with mutations in IDH2

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?

Memorial Sloan Kettering Cancer Center

Lead Sponsor

Trials

1,998

Recruited

602,000+

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]

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 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]

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 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 (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, 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]

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. trialx.com trialx.com/clinical-trials/listings/325101/enasidenib-for-patients-with-clonal-cytopenia-of-undetermined-significance-and-mutations-in-idh2a-decentralized-trial/

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

4. 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 ...

5. 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.

6. frontiersin.org frontiersin.org/journals/hematology/articles/10.3389/frhem.2024.1419323/full

Clonal cytopenia of undetermined significance: definitions ... In this review, we focus on CCUS and the current understanding of its classification, risk stratification and potential therapeutic targets.