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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to evaluate the effectiveness of enasidenib as a maintenance treatment for individuals with acute myeloid leukemia (AML) who have the IDH2 mutation. It targets those who have undergone a stem cell transplant and are in remission, yet require ongoing management. Participants must have been diagnosed with AML with the IDH2 mutation and have already received a stem cell transplant. The trial seeks to determine if enasidenib can prevent cancer recurrence by targeting enzymes essential for cancer cell growth. As a Phase 2 trial, this research focuses on assessing the treatment's efficacy in an initial, smaller group of participants.

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.

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

Research has shown that enasidenib is generally safe and well-tolerated in patients with IDH2-mutated myeloid diseases. In earlier studies, most patients handled the treatment well, though some experienced side effects. Specifically, 14% of patients developed differentiation syndrome, a condition that can be serious if not treated quickly. Overall, the treatment appears promising, but awareness of these possible side effects is important. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for acute myeloid leukemia?

Unlike the standard chemotherapy treatments for Acute Myeloid Leukemia (AML), which typically target rapidly dividing cells, Enasidenib offers a unique approach by targeting the mutant IDH2 enzyme. This enzyme is often involved in the growth of leukemia cells, and by inhibiting it, Enasidenib can potentially stop the progression of the disease at its source. Researchers are excited about this treatment because it specifically addresses the genetic mutations driving the cancer, offering hope for improved outcomes with potentially fewer side effects than conventional chemotherapy.

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

Research has shown that enasidenib, which participants in this trial will receive, works well for patients with acute myeloid leukemia (AML) who have an IDH2 mutation. Studies have found that it helps patients live longer and increases the chances of their cancer going into complete remission compared to usual treatments. In one study, 37% of patients saw their cancer respond to the treatment. Another study found a 40.3% response rate in patients with hard-to-treat AML. These findings suggest that enasidenib could be a helpful option for managing AML with an IDH2 mutation. ^{2 6 7 8 9}

Who Is on the Research Team?

Amandeep Salhotra

Principal Investigator

City of Hope Medical Center

Are You a Good Fit for This Trial?

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.

Women of childbearing potential (WOCBP): negative urine or serum pregnancy test. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required

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 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, 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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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 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, 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 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]

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. Enasidenib represents a valuable ...

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. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5572791/

Enasidenib in mutant IDH2 relapsed or refractory acute ... Key Points. Enasidenib, a selective inhibitor of mutant IDH2 enzymes, was safe and well tolerated in patients with IDH2-mutated myeloid malignancies.

7. investor.agios.com investor.agios.com/news-releases/news-release-details/updated-data-phase-1-trial-oral-idhifar-enasidenib-demonstrate-0

Updated Data from Phase 1 Trial of Oral IDHIFA® ... The overall safety profile observed for enasidenib was consistent with previously reported data. Twenty-four percent of patients had treatment-related ...

8. idhifapro.com idhifapro.com/r-r-aml

About Relapsed/Refractory AML | IDHIFA® (enasidenib) for ... In the clinical trial, 14% of patients treated with IDHIFA experienced differentiation syndrome, which may be life-threatening or fatal if not treated.

9. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6347084/

An Oral IDH2 Inhibitor for the Treatment of Acute Myeloid ... Enasidenib is a novel treatment option for patients with relapsed or refractory AML harboring an IDH2 mutation. Although not directly compared to other ...