A Study of Enasidenib in People With T-Cell Lymphoma

NCT06756308 | Recruiting Phase 2 FDA Drug

• 1 other identifier: 23-269
• Study Type: interventional
• Target: 25
• Locations: 1 country
• Sites: 8

Brief Summary

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.

Conditions

T-cell Lymphoma

Keywords

Enasidenib; Rituximab; IDH2-mutant; 23-269

Outcome Measures

Primary Outcomes (1)

• response rate

  a 20% response rate is undesirable and 45% is desirable

  1 year

Study Arms (1)

Enasidenib and rituximab

EXPERIMENTAL

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.

Drug: Enasidenib; Drug: Rituximab

Interventions

Enasidenib DRUG

Enasidenib 100 mg daily on 28-day cycles.

Enasidenib and rituximab

Rituximab DRUG

IV rituximab 375 mg/m² weekly for the first month, and monthly thereafter on 28-day cycles, for a total of four months of rituximab.

Enasidenib and rituximab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Screening Cohort (non-MSK patients only)
• Age ≥18 years at time of consent
• Has freely given written informed consent to participate in the study
• Treatment Cohort:
• Pathologically-confirmed AITL at the enrolling institution, with confirmed IDH2 mutation (by MSK ddPCR). For R/R patients, disease must have relapsed or progressed after at least one systemic therapy, diagnostic tumor samples have at least 5% tumor.
• Age ≥18 years at time of enrollment
• Previous systemic anti-cancer therapy for AITL must have been discontinued at least 2 weeks or 5 half-lives (whichever is longer) prior to treatment.

You may not qualify if:

• ii) Patients who have received localized RT as part of their immediate prior therapy may be allowed to enroll with shorter washout period after discussion with the MSKCC Principal Investigator iii) Systemic corticosteroids must be tapered to 25 mg/day prednisone (or equivalent) upon start of investigational treatment iv) Topical steroids for treating cutaneous involvement of AITL is permitted
• Performance status, as assessed in the ECOG grading system, ≤2
• Laboratory criteria (use of GCSF and/or blood product transfusions to reach eligibility criteria must be discussed with the MSK PI on a case-by-case basis): i) Absolute neutrophil count ≥1.0 K/μL or ≥0.5 K/μL if due to lymphoma ii) Platelet count ≥80 K/μl or ≥50 K/μl if due to lymphoma iii) Calculated creatinine clearance ≥30 mL/min by the Modification of Diet in Renal Disease (MDRD) glomerular filtration rate iv) Total bilirubin ≤1.5x upper limit of normal (ULN) or ≤3x ULN if documented hepatic involvement with lymphoma, or ≤5x ULN if history of Gilbert's syndrome; AST and ALT ≤ 3x ULN; ≤ 5x ULN if due to lymphoma involvement
• Measurable disease, defined by either of:
• Revised International Working Group Classification for systemic lymphoma(13)
• Atypical T lymphocytes quantifiable by flow cytometry or morphology in the peripheral blood or bone marrow
• Women of reproductive potential\* must have a negative serum or urine β human chorionic gonadotropin (β-hCG) pregnancy test. All women of reproductive potential must agree to use adequate methods of birth control throughout the study and for 30 days after the last dose of study drug. \*A woman of reproductive potential is a sexually mature woman who: has not undergone a hysterectomy or bilateral oophorectomy; or has not been naturally postmenopausal for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months)
• Women must agree to not breastfeed during the study period
• Male subjects must agree to practice true abstinence from sexual intercourse or to the use of highly effective contraceptive methods with non-pregnant female partners of childbearing potential at screening and throughout the course of the study, and should avoid conception with their partners during the course of the study and for 4 months following the last study treatment
• Subject is willing and able to adhere to the study visit schedule and other protocol requirements
• Any serious medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from signing the informed consent form.
• On immunosuppressive therapy post-allogeneic stem cell transplantation at the time of screening, or with clinically significant graft-versus-host disease (GVHD). The use of a stable dose of oral steroid post-HSCT and/or topical steroids for ongoing skin GVHD is permitted after discussion with the study PI
• Subject has persistent, clinically significant non-hematologic toxicities grade \>1 or not to baseline level from prior therapies besides alopecia or neuropathy
• Pregnant women
• History of chronic liver disease, veno-occlusive disease, or alcohol abuse

Sponsors & Collaborators

• Memorial Sloan Kettering Cancer Center: lead
• Bristol-Myers Squibb: collaborator
• The Leukemia and Lymphoma Society: collaborator

Study Sites (8)

Dana Farber Cancer Institute (Data Collection Only)

Boston, Massachusetts, 02115, United States

NOT YET RECRUITING

Memorial Sloan Kettering at Basking Ridge (Limited Protocol Activities)

Basking Ridge, New Jersey, 07920, United States

RECRUITING

Memorial Sloan Kettering Cancer Center (Limited Protocol Activities)

Basking Ridge, New Jersey, 07920, United States

RECRUITING

Memorial Sloan Kettering Monmouth (Limited protocol activities)

Middletown, New Jersey, 07748, United States

RECRUITING

Memorial Sloan Kettering Bergen (Limited Protocol Activities)

Montvale, New Jersey, 07645, United States

RECRUITING

Memorial Sloan Kettering Suffolk-Commack (Limited protocol activity)

Commack, New York, 11725, United States

RECRUITING

Memorial Sloan Kettering Westchester (All protocol activities)

Harrison, New York, 10604, United States

RECRUITING

Memorial Sloan Kettering Nassau (Limited protocol activities)

Uniondale, New York, 11553, United States

RECRUITING

Related Links

• Memorial Sloan Kettering Cancer Center

MeSH Terms

Conditions

Lymphoma, T-Cell

Interventions

enasidenib; Rituximab

Condition Hierarchy (Ancestors)

Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Zachary Epstein-Peterson, MD

  Memorial Sloan Kettering Cancer Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Zachary Epstein-Peterson, MD

CONTACT

646-608-4176; epsteinz@mskcc.org

Steven Horwitz, MD

CONTACT

646-608-3725

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 27, 2024
• First Posted: January 2, 2025
• Study Start: December 24, 2024
• Primary Completion (Estimated): December 1, 2027
• Study Completion (Estimated): December 1, 2027
• Last Updated: December 23, 2025

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will share

Locations

US (8)