Enasidenib for Acute Myeloid Leukemia

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: City of Hope Medical Center

Disqualifiers: Active infection, Uncontrolled illness, Active malignancy, 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: 26

Duration: 24 months

35 Participants Needed

Trial Summary

What is the purpose of this trial?

This phase II trial studies the side effects of using enasidenib as maintenance therapy in treating patients with acute myeloid leukemia with IDH2 mutation following donor stem cell transplant. Enasidenib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth.

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 is best to discuss this with the study team or your doctor to understand how your current medications might interact with the trial treatment.

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

Enasidenib has shown promising results in treating acute myeloid leukemia with IDH2 mutations, with clinical trials indicating it induced responses in 40.3% of patients and improved median overall survival to 9.3 months. It is approved in the USA for relapsed or refractory cases, demonstrating its effectiveness in these challenging situations. ^{1 2 3 4 5}

Is Enasidenib safe for humans?

Enasidenib, also known as Idhifa, has been studied for safety in patients with acute myeloid leukemia and is generally considered safe, with clinical trials showing it may improve survival in some patients. ^{1 3 4 5 6}

How is the drug enasidenib unique in treating acute myeloid leukemia?

Enasidenib is unique because it specifically targets and inhibits mutant IDH2 proteins, which are involved in the development of acute myeloid leukemia. Unlike traditional chemotherapy, enasidenib is taken orally and works by promoting the differentiation of immature white blood cells into mature, functional cells, offering a novel approach for patients with relapsed or refractory AML with an IDH2 mutation. ^{1 2 3 4 7}

Research Team

Amandeep Salhotra

Principal Investigator

City of Hope Medical Center

Eligibility Criteria

This trial is for adults with acute myeloid leukemia (AML) and an IDH2 mutation who've had a donor stem cell transplant. They must not be pregnant, have good organ function, no severe active infections or other cancers, and agree to birth control. People with Gilbert's disease or uncontrolled illnesses can't join.

Inclusion Criteria

Seronegative for human immunodeficiency virus (HIV) antigen/antibody (Ag/Ab) combo, hepatitis C virus (HCV), active hepatitis B virus (HBV) (surface antigen negative), and syphilis (rapid plasma reagin [RPR]). If positive, hepatitis C ribonucleic acid (RNA) quantitation must be performed

My platelet count is at least 20,000/mm^3, or I'm being treated for specific infections with a lower count.

My liver function tests are normal or near normal.

Exclusion Criteria

Any other condition that would, in the investigator's judgment, contraindicate the patient's participation in the clinical study due to safety concerns with clinical study procedures

I am not pregnant or breastfeeding.

Prospective participants, who, in the opinion of the investigator, may not be able to comply with all study procedures (including compliance issues related to feasibility/logistics)

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, with treatment repeating every 28 days for up to 24 cycles

24 months

Monthly visits for 24 cycles

Follow-up

Participants are monitored for safety and effectiveness after treatment completion, with follow-up at 30 days and periodically up to 2 years

24 months

Periodic visits up to 2 years

Treatment Details

Interventions

• Enasidenib Mesylate

Trial Overview Enasidenib Mesylate is being tested as a maintenance therapy for AML patients post-stem cell transplant. The study aims to see if this drug can prevent cancer growth by inhibiting certain enzymes needed by cancer cells.

Participant Groups

Group I: Treatment (enasidenib mesylate) Experimental Treatment 1 Intervention

Patients receive enasidenib PO QD on days 1-28. Treatment repeats every 28 days for up to 24 cycles in the absence of disease progression or unacceptable toxicity.

Who Is Running the Clinical Trial?

City of Hope Medical Center

Lead Sponsor

Trials

614

Recruited

1,924,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Findings from Research

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 (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, 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]

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]

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 mesylate, an IDH2 inhibitor approved for relapsed/refractory acute myeloid leukemia (AML), can cause a differentiation syndrome (IDH-DS) in about 12% of patients, characterized by symptoms like dyspnea and fever, typically occurring around 30 days after treatment begins.

IDH-DS can be effectively managed with systemic corticosteroids, and while treatment may need to be interrupted for some patients, permanent discontinuation is rarely necessary, highlighting the importance of prompt recognition and management of this syndrome.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Differentiation Syndrome Associated With Enasidenib, a Selective Inhibitor of Mutant Isocitrate Dehydrogenase 2: Analysis of a Phase 1/2 Study. Fathi, AT., DiNardo, CD., Kline, I., et al.[2022]

References

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

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

2. England pubmed.ncbi.nlm.nih.gov

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

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

Enasidenib: First Global Approval. [2022]

4. Netherlands pubmed.ncbi.nlm.nih.gov

Enasidenib: First Mutant IDH2 Inhibitor for the Treatment of Refractory and Relapsed Acute Myeloid Leukemia. [2022]

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

Positive First Trial of Enasidenib for AML. [2022]

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

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

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

Differentiation Syndrome Associated With Enasidenib, a Selective Inhibitor of Mutant Isocitrate Dehydrogenase 2: Analysis of a Phase 1/2 Study. [2022]