Enasidenib for Acute Myeloid Leukemia

Not currently recruiting at 30 trial locations

Age: < 65

Sex: Any

Trial Phase: Phase 2

Sponsor: Children's Oncology Group

Must not be taking: Corticosteroids, Investigational drugs, Anti-cancer agents, Anti-GVHD agents

Disqualifiers: Down syndrome, Pregnancy, Breastfeeding, 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: Unknown

Duration: Up to 12 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how well enasidenib (also known as Idhifa) works for children and young adults with a challenging type of blood cancer called acute myeloid leukemia (AML), particularly when it has returned or resisted other treatments. Enasidenib targets a specific mutation in a protein called IDH2, which contributes to the growth of leukemia cells. Participants must have AML that is either relapsed or resistant to standard chemotherapy and must possess this specific IDH2 mutation. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

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.

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

Research has shown that enasidenib is approved by the FDA for treating adults with acute myeloid leukemia (AML) that involves a specific change in the IDH2 gene, indicating some known safety in people. Studies have found that while enasidenib can help treat AML, it may cause side effects. Common side effects include nausea, vomiting, and diarrhea. There is also a risk of tumor lysis syndrome, a serious condition that occurs when cancer cells break down quickly, releasing substances into the blood that can harm the kidneys and heart. Doctors often prescribe medications to help prevent this.

Overall, enasidenib is usually well-tolerated, but awareness of these side effects is important. Trial participants will be closely monitored to manage any issues that arise. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Enasidenib is unique because it specifically targets a mutated enzyme called IDH2, which is often found in patients with acute myeloid leukemia (AML). While traditional treatments for AML, like chemotherapy, broadly attack rapidly dividing cells, enasidenib works differently by directly addressing this genetic mutation. This targeted approach can potentially lead to fewer side effects and improved outcomes for patients whose leukemia is driven by this mutation. Researchers are excited about enasidenib because it offers a more personalized treatment option, potentially providing a new avenue of hope for those who don't respond well to standard therapies.

What evidence suggests that enasidenib might be an effective treatment for acute myeloid leukemia?

Research has shown that enasidenib, the treatment under study in this trial, works well for patients with acute myeloid leukemia (AML) who have a specific change in the IDH2 protein. Studies have found that enasidenib helps patients live longer and increases the chances of complete remission compared to standard treatments. In a group of patients whose AML returned or did not respond to other treatments, enasidenib led to a positive response in 40.3% of cases. Additionally, patients taking enasidenib experienced better survival rates and fewer complications. These findings suggest that enasidenib can be a helpful treatment option for people with this specific type of AML. ^{4 6 7 8 9}

Who Is on the Research Team?

Sara Zarnegar-Lumley

Principal Investigator

Children's Oncology Group

Are You a Good Fit for This Trial?

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.

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).

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• Enasidenib

Trial Overview The 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.

How Is the Trial Designed?

Group I: Treatment (enasidenib) Experimental Treatment 5 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

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+

Published Research Related to This Trial

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 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 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.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Enasidenib Approved for AML, but Best Uses Unclear. [2018]

Enasidenib, an allosteric inhibitor of mutated IDH2, has shown a good safety and efficacy profile in treating relapsed or refractory acute myeloid leukemia (AML), with a reported overall survival rate of 9.3 months for patients whose disease has relapsed.

In clinical trials, Enasidenib demonstrated an overall survival rate of 40.3% and a complete response rate of 19.3%, indicating its potential as a significant treatment option for AML, although it is associated with adverse effects like elevated bilirubin levels and differentiation syndrome.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Enasidenib: First Mutant IDH2 Inhibitor for the Treatment of Refractory and Relapsed Acute Myeloid Leukemia. Dogra, R., Bhatia, R., Shankar, R., 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 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]

The investigational drug enasidenib, which targets IDH2 mutations, has shown a safety profile and potential to improve survival in patients with relapsed or refractory acute myeloid leukemia.

In a clinical trial, enasidenib induced responses in 40.3% of patients, leading to a median overall survival of 9.3 months.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Positive First Trial of Enasidenib for AML. [2022]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/36108427/

Real-world clinical outcomes with enasidenib in relapsed ... Results from this real-world study confirm the effectiveness of enasidenib among patients with IDH2-mutated RR AML and demonstrate that hospitalizations were ...

2. sciencedirect.com sciencedirect.com/science/article/abs/pii/S2152265025017215

AML-751: Clinical Efficacy and Safety of Enasidenib in ... Regarding secondary efficacy outcomes, pooled OS and EFS rates were 47% (95% CI, 0.23–0.73; P < 0.0001) and 33% (95% CI, 0.17–0.55; P = 0.0448). The incidence ...

3. annalsofoncology.org annalsofoncology.org/article/S0923-7534(24)01399-1/fulltext

MO61-6 Efficacy of enasidenib on acute myeloid leukemia Enasidenib demonstrated a significant improvement in overall survival and complete remission rate compared to standard therapy.

4. investor.agios.com investor.agios.com/news-releases/news-release-details/new-data-phase-12-trial-oral-idhifar-enasidenib-demonstrate-0

New Data from Phase 1/2 Trial of Oral IDHIFA® ... Data from 214 of the R/R AML patients with an IDH2 mutation who were treated at the recommended Phase 2 starting dose of 100 mg daily demonstrated a 37 percent ...

5. consultqd.clevelandclinic.org consultqd.clevelandclinic.org/enasidenib-effective-treatment-for-refractory-acute-myeloid-leukemia

Enasidenib Effective Treatment for Refractory Acute Myeloid ... Enasidenib at doses of 50 mg to 650 mg daily produced an overall response rate (ORR) of 40.3 percent (95% CI, 33-38) and a 19.3 percent (95% CI, ...

6. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/label/2025/209606s007lbl.pdf

IDHIFA® (enasidenib) tablets, for oral use - accessdata.fda.gov IDHIFA is a prescription medicine used to treat people with acute myeloid leukemia (AML) with an isocitrate dehydrogenase-2 (IDH2) mutation whose disease has ...

7. idhifa.com idhifa.com/

IDHIFA®: For Relapsed / Refractory Acute Myeloid Leukemia ... Learn more about IDHIFA® (enasidenib) for patients with relapsed/refractory acute myeloid leukemia (AML) with an IDH2 mutation. See safety info and BOXED ...

8. mayoclinic.org mayoclinic.org/drugs-supplements/enasidenib-oral-route/description/drg-20406484

Enasidenib (oral route) - Side effects & dosage This medicine may increase risk of a serious condition called tumor lysis syndrome. Your doctor may give you a medicine to help prevent this.

9. fda.gov fda.gov/drugs/drug-safety-and-availability/fda-warns-symptoms-serious-condition-affecting-blood-cells-are-not-being-recognized-leukemia

FDA warns that symptoms of a serious condition Idhifa ... FDA warns that symptoms of a serious condition affecting the blood cells are not being recognized with the leukemia medicine Idhifa (enasidenib).