Enasidenib for Clonal Cytopenia

Recruiting at 12 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

4 Participants Needed

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.

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.

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

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 who had relapsed or were resistant to other treatments. This suggests it may also be beneficial for other conditions involving similar mutations, 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. ^{1 2 3 6 7}

Research Team

Eytan Stein, MD

Principal Investigator

Memorial Sloan Kettering Cancer Center

Eligibility Criteria

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.

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

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

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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, 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 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, 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 (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. 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]

2. 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]

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

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

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

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

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

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

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

Enasidenib: First Global Approval. [2022]

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

Enasidenib. [2019]