Enasidenib for T-Cell Lymphoma

Recruiting at 7 trial locations

Overseen By Zachary Epstein-Peterson, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Memorial Sloan Kettering Cancer Center

Disqualifiers: Diabetes, Hypertension, Bipolar, 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

Compensation: Varies

Number of Visits: Unknown

Duration: Up to 1 year

25 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether enasidenib, alone or with rituximab, is a safe treatment for angioimmunoblastic T-cell lymphoma (AITL) with an IDH2 mutation. The researchers aim to assess the effectiveness of these treatments in managing this specific cancer type. Individuals with AITL that has recurred or worsened after other treatments and who have an IDH2 mutation may be suitable candidates for this study. As a Phase 2 trial, the research measures the treatment's effectiveness in an initial, smaller group of participants.

Will I have to stop taking my current medications?

The trial requires that you stop any previous systemic anti-cancer therapy for at least 2 weeks or 5 half-lives before starting the treatment. Systemic corticosteroids must be reduced to 25 mg/day prednisone (or equivalent) when beginning the trial treatment.

Is there any evidence suggesting that enasidenib and rituximab are likely to be safe for humans?

Previous studies have shown that enasidenib was generally well tolerated. Healthy participants taking doses of 50 mg, 100 mg, and 300 mg did not experience major issues. However, other research reported serious side effects in about 24% of patients, including IDH differentiation syndrome, which affects blood cells, and other issues like increased white blood cells and tumor breakdown.

The safety evidence from these studies guides the current trial. Since enasidenib is already in a later phase of testing, researchers have some safety information, but they continue to assess its safety for people with angioimmunoblastic T-cell lymphoma. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Unlike the standard treatments for T-cell lymphoma, which often include chemotherapy and radiation, enasidenib works by specifically targeting and inhibiting the mutant IDH2 enzyme. This precision approach could lead to fewer side effects and a more direct attack on cancer cells. Additionally, for patients with co-occurring B-cell lymphoproliferation, the combination with rituximab, a monoclonal antibody, offers a tailored treatment strategy that addresses the complexity of their condition. Researchers are excited about enasidenib because it represents a novel, targeted therapy that might improve outcomes for patients with specific genetic mutations.

What evidence suggests that enasidenib might be an effective treatment for angioimmunoblastic T-cell lymphoma?

Research has shown that enasidenib, a drug targeting the IDH2 enzyme mutation, holds potential for treating cancers with this mutation, such as angioimmunoblastic T-cell lymphoma (AITL). In earlier studies involving patients with acute myeloid leukemia, about 40% experienced significant improvement in cancer symptoms after using enasidenib. These improvements often began after about one month, with the best results observed around three months. This trial will evaluate enasidenib for individuals with AITL and the IDH2 mutation. Participants with evidence of co-occurring B-cell lymphoproliferation will also receive rituximab, which may enhance treatment effectiveness. ^{1 6 7 8 9}

Who Is on the Research Team?

Zachary Epstein-Peterson, MD

Principal Investigator

Memorial Sloan Kettering Cancer Center

Are You a Good Fit for This Trial?

This trial is for adults over 18 with angioimmunoblastic T-cell lymphoma (AITL) that has relapsed or progressed after treatment and carries an IDH2 mutation. Participants must have finished previous cancer treatments at least 2 weeks prior, have a decent performance status (ECOG ≤2), and meet specific lab criteria.

Inclusion Criteria

My AITL cancer has an IDH2 mutation and has worsened after treatment.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive oral enasidenib 100 mg daily on 28-day cycles. Patients with co-occurring B-cell LPB receive IV rituximab weekly for the first month and monthly thereafter for up to four months.

Up to 1 year

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Enasidenib
• Rituximab

Trial Overview The study tests the safety of Enasidenib alone or combined with Rituximab in treating AITL with an IDH2 mutation. It aims to determine if these drugs are safe options for patients who've seen their disease return or worsen after initial therapy.

How Is the Trial Designed?

Group I: Enasidenib and rituximab Experimental Treatment 2 Interventions

Screening Cohort (Non-MSK Patients only) Non-MSK patients will send research tissue samples to MSK for ddPCR analysis to assess IDH2 mutation. Once mutation is confirmed they may be consented to the treatment portion of the trial. All patients will receive oral enasidenib 100 mg daily on 28-day cycles. Patients with evidence of a co-occurring B-cell lymphoproliferation (via tumor morphology, flow cytometry, or B-cell clonality) will be administered IV rituximab 375 mg/m² weekly for the first month, and monthly for 3 months thereafter on 28-day cycles, for a total of four months of rituximab. If B-cell proliferation persists at the end of the 4-month rituximab treatment period, continue treatment with monthly rituximab until no evidence of B-cell lymphoproliferation is seen.

Who Is Running the Clinical Trial?

Memorial Sloan Kettering Cancer Center

Lead Sponsor

Trials

1,998

Recruited

602,000+

Bristol-Myers Squibb

Industry Sponsor

Trials

2,731

Recruited

4,127,000+

Headquarters

New York City, USA

Known For

Oncology & Cardiovascular

Top Products

Eliquis, Opdivo, Revlimid, Orencia

Christopher Boerner

Bristol-Myers Squibb

Chief Executive Officer since 2023

PhD in Business Administration from the Haas School of Business, University of California, Berkeley; BA in Economics and History from Washington University in St. Louis

Deepak L. Bhatt

Bristol-Myers Squibb

Chief Medical Officer since 2024

MD from Yale University; MSc in Clinical Epidemiology from the University of Pennsylvania

The Leukemia and Lymphoma Society

Collaborator

Trials

87

Recruited

26,200+

Published Research Related to This Trial

Copanlisib is a pan-specific PI3K inhibitor that has shown increased efficacy against B-cell malignancies, particularly in treating relapsed follicular lymphoma, and has received accelerated FDA approval for this use.

The development of copanlisib and other PI3K inhibitors offers effective treatment options with a favorable toxicity profile, making them promising alternatives for patients with high relapse rates in indolent B-cell non-Hodgkin lymphomas.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Spotlight on copanlisib and its potential in the treatment of relapsed/refractory follicular lymphoma: evidence to date. Mensah, FA., Blaize, JP., Bryan, LJ.[2020]

Alisertib (MLN8237), an oral Aurora A kinase inhibitor, has demonstrated the ability to reduce cell proliferation and induce apoptosis in various tumor cell lines, making it a promising treatment for aggressive peripheral T-cell lymphomas.

Currently undergoing Phase III trials, alisertib has shown single-agent antitumor activity in animal models and potential effectiveness in patients with relapsed or refractory peripheral T-cell lymphoma, highlighting its importance in developing new therapies for this challenging condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The role of alisertib in treatment of peripheral T-cell lymphomas. Gallop-Evans, E.[2015]

Current treatments for T cell lymphomas (TCL), like CHOP, are less effective than in B cell lymphomas, leading to high failure rates and relapses, highlighting the need for new therapies.

Recent advances in understanding TCL biology have paved the way for promising new targeted therapies, such as histone deacetylase inhibitors and anaplastic lymphoma kinase inhibitors, which have shown clinical success and could significantly improve patient outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Novel targeted therapies of T cell lymphomas. Iżykowska, K., Rassek, K., Korsak, D., et al.[2023]

Enzastaurin showed modest antitumor activity in patients with various types of non-Hodgkin lymphomas, with response rates of 20% in follicular lymphomas grade 3 and 18.2% in cutaneous T-cell lymphoma among a heavily pretreated group of patients.

The treatment was generally well tolerated, with most side effects being mild (grade 1/2), including diarrhea and peripheral edema, indicating a favorable safety profile for patients who had limited treatment options.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A multicenter, open-label, noncomparative screening study of enzastaurin in adult patients with non-Hodgkin lymphomas. Forsyth, CJ., Gomez-Almaguer, D., Camargo, JF., et al.[2013]

In a study involving 21 patients with relapsed or refractory non-Hodgkin lymphoma, apatinib demonstrated a promising overall response rate of 47.6%, indicating significant antitumor activity.

The treatment was generally well-tolerated, with most adverse events being mild to moderate, including proteinuria and hypertension, suggesting that apatinib could be a safe option for these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An open label, single-armed, exploratory study of apatinib (a novel VEGFR-2 tyrosine kinase inhibitor) in patients with relapsed or refractory non-Hodgkin lymphoma. Li, L., Xiao, S., Zhang, L., et al.[2022]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06756308

A Study of Enasidenib in People With T-Cell Lymphoma The researchers are doing this study to find out whether enasidenib is a safe treatment for people with angioimmunoblastic T-cell lymphoma (AITL) that has ...

2. sciencedirect.com sciencedirect.com/science/article/pii/S0006497123047638

Final Results of the Phase Ib/II Study Evaluating ... The median time to initial response was 1 month (range, 0.9 - 5.7), and the median time to best response was 2.8 months (range, 0.9 - 12.5). The ...

3. ashpublications.org ashpublications.org/blood/article/140/Supplement%201/2016/489941/A-Risk-Adapted-Study-to-Assess-the-Efficacy-of

A Risk-Adapted Study to Assess the Efficacy of Enasidenib ... Seven patients (41%, 95% CI 18-67) achieved CR/CRi on ENA + AZA. With a median follow up of 41.1 months, the median overall survival from the ...

4. bloodcancerunited.org bloodcancerunited.org/research/award/targeting-mutant-idh2-angioimmunoblastic-t-cell-lymphoma

Targeting mutant IDH2 in angioimmunoblastic T-cell ... In clinical trials involving patients with acute myeloid leukemia, the mutant IDH2 enzyme inhibitor enasidenib induced a response in ~40% of ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6041864/

The role of enasidenib in the treatment of mutant IDH2 acute ... The median time to achieve complete remission was 3.8 months (range 0.5–11.2 months), with a median duration of response of 8.8 months. Seventeen patients (10%) ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6199364/

Pharmacokinetics and safety of Enasidenib following ... Regarding safety, Enasidenib was well tolerated when administered to healthy male subjects at the doses of 50 mg, 100 mg, and 300 mg. The ...

7. 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 ... The manufacturer's safety report, which included the period of May 1, 2018 to July 31, 2018, reported five cases of death associated with ...

8. 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® ... Twenty-four percent of patients had treatment-related serious adverse events (SAEs), notably IDH differentiation syndrome (8%), leukocytosis (4%), tumor lysis ...

9. bpspubs.onlinelibrary.wiley.com bpspubs.onlinelibrary.wiley.com/doi/am-pdf/10.1002/prp2.436

Pharmacokinetics and safety of Enasidenib following single ... Abstract. The aim of this study was to assess and compare the pharmacokinetics (PK) and safety of Enasidenib in healthy adult male Japanese ...