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

Trial Summary

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.

How is the drug Enasidenib unique for treating T-cell lymphoma?

Enasidenib is unique for treating T-cell lymphoma because it targets specific genetic mutations, unlike traditional chemotherapy regimens like CHOP, which have high failure rates in T-cell lymphomas. This approach is part of a new wave of gene-targeted therapies aiming to improve outcomes for these aggressive cancers. ^{1 2 3 4 5}

What is the purpose of this trial?

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 an IDH2 mutation. The researchers will look at the safety of enasidenib when it is given alone or in combination with the drug rituximab.

Research Team

Steven Horwitz, MD

Principal Investigator

Memorial Sloan Kettering Cancer Center

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

Group I: Enasidenib and rituximab Experimental Treatment 2 Interventions

All patients will receive oral enasidenib 100 mg daily on 28-day cycles. Patients with evidence of a co-occuring B-cell LPB will also received IV rituximab 375 mg/m² weekly for the first month, and monthly thereafter (four total months of rituximab provided no evidence of active EBV or B-cell lymphoproliferation)) on 28-day cycles. Treatment may continue until volitional patient withdrawal, disease progression, unacceptable toxicity, recommended termination by the treating physician, or termination of the study.

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+

Findings from Research

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]

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]

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]

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]

References

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

Spotlight on copanlisib and its potential in the treatment of relapsed/refractory follicular lymphoma: evidence to date. [2020]

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

Novel targeted therapies of T cell lymphomas. [2023]

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

A multicenter, open-label, noncomparative screening study of enzastaurin in adult patients with non-Hodgkin lymphomas. [2013]

4. England pubmed.ncbi.nlm.nih.gov

The role of alisertib in treatment of peripheral T-cell lymphomas. [2015]

5. United States 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. [2022]