10 Participants Needed

Enasidenib for Acute Myeloid Leukemia

Recruiting at 27 trial locations
No Placebo GroupAll trial participants will receive the active study treatment (no placebo)
Prior Safety DataThis treatment has passed at least one previous human trial
Approved in 2 JurisdictionsThis treatment is already approved in other countries

Trial Summary

What is the purpose of this trial?

This phase II trial studies the side effects of enasidenib and sees how well it works in treating pediatric patients with acute myeloid leukemia that has come back after treatment (relapsed) or has been difficult to treat with chemotherapy (refractory). Patients must also have a specific genetic change, also called a mutation, in a protein called IDH2. Enasidenib may stop the growth of cancer cells by blocking the mutated IDH2 protein, which is needed for leukemia cell growth.

Will I have to stop taking my current medications?

The trial requires that you stop taking certain medications before starting enasidenib. Specifically, you must discontinue drugs with a narrow therapeutic range that are sensitive to certain enzymes, as well as the drug rosuvastatin, more than 5 half-lives before the first dose of enasidenib. Additionally, you cannot be on other anti-cancer agents or investigational drugs during the trial.

What data supports the effectiveness of the drug Enasidenib for treating acute myeloid leukemia?

Research shows that Enasidenib, a drug targeting specific genetic mutations in acute myeloid leukemia, has been effective in some patients, with 40.3% showing positive responses and a median survival of 9.3 months. It is approved for use in patients with relapsed or refractory acute myeloid leukemia with IDH2 mutations.12345

Is Enasidenib safe for humans?

Enasidenib, also known as Idhifa, has been evaluated in clinical trials for safety in patients with acute myeloid leukemia, and it is generally considered safe, although the FDA approved it with less supporting evidence than usual.13456

What makes the drug Enasidenib unique for treating acute myeloid leukemia?

Enasidenib is unique because it specifically targets and inhibits mutant IDH2 proteins, which are involved in the development of certain types of acute myeloid leukemia. It is taken orally and is particularly used for patients with relapsed or refractory AML who have an IDH2 mutation, offering a targeted approach compared to traditional chemotherapy.23567

Research Team

SZ

Sara Zarnegar-Lumley

Principal Investigator

Children's Oncology Group

Eligibility Criteria

This trial is for patients with acute myeloid leukemia that's returned or hasn't responded to chemo, and have an IDH2 mutation. They should be able to perform daily activities at least halfway normally, not have certain AML types like Down syndrome-related or t(15;17), no known allergies to enasidenib, and mustn't be pregnant or breastfeeding. Participants need proper kidney function, acceptable blood counts, and can't be on conflicting medications.

Inclusion Criteria

I consider my donor lymphocyte infusion as a re-treatment effort.
My chemotherapy treatments are considered separate attempts.
I haven't taken any cancer drugs that lower blood counts in the last 7 days.
See 34 more

Exclusion Criteria

I am not on any cancer treatments, except possibly hydroxyurea for leukemia.
I have been on a stable or decreasing dose of corticosteroids for at least 7 days.
My AML is not linked to Down syndrome or t(15;17).
See 8 more

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive enasidenib orally once daily on days 1-28. Treatment repeats every 28 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity.

Up to 12 months
Monthly visits for each cycle

Follow-up

Participants are monitored for safety and effectiveness after treatment completion, with follow-up at 30 days, then periodically up to 1 year.

Up to 1 year
Periodic visits

Treatment Details

Interventions

  • Enasidenib
Trial OverviewThe trial is testing the effectiveness and side effects of a drug called enasidenib in treating relapsed/refractory acute myeloid leukemia with an IDH2 mutation. It involves collecting biospecimens and performing bone marrow procedures to see if blocking the mutated protein with enasidenib stops cancer growth.
Participant Groups
1Treatment groups
Experimental Treatment
Group I: Treatment (enasidenib)Experimental Treatment5 Interventions
Patients receive enasidenib PO QD on days 1-28. Treatment repeats every 28 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo bone marrow aspiration and/or biopsy and collection of blood on study.

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

Find a Clinic Near You

Who Is Running the Clinical Trial?

Children's Oncology Group

Lead Sponsor

Trials
467
Recruited
241,000+

National Cancer Institute (NCI)

Collaborator

Trials
14,080
Recruited
41,180,000+

Findings from Research

Enasidenib is a targeted therapy approved by the FDA for patients with refractory or relapsed acute myeloid leukemia (AML) who have a specific mutation (IDH2).
The drug has shown the ability to induce remissions in some patients and may decrease the need for blood transfusions, although its approval was based on less supporting evidence than typically required.
Enasidenib Approved for AML, but Best Uses Unclear.[2018]
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.
An evaluation of enasidenib for the treatment of acute myeloid leukemia.Del Principe, MI., Paterno, G., Palmieri, R., et al.[2019]
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.
Modeling and simulation of the endogenous CYP3A induction marker 4β-hydroxycholesterol during enasidenib treatment.Li, Y., Connarn, JN., Chen, J., et al.[2022]

References

Enasidenib Approved for AML, but Best Uses Unclear. [2018]
An evaluation of enasidenib for the treatment of acute myeloid leukemia. [2019]
Modeling and simulation of the endogenous CYP3A induction marker 4β-hydroxycholesterol during enasidenib treatment. [2022]
Positive First Trial of Enasidenib for AML. [2022]
Enasidenib: First Mutant IDH2 Inhibitor for the Treatment of Refractory and Relapsed Acute Myeloid Leukemia. [2022]
Enasidenib: First Global Approval. [2022]
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]