A Phase 2 Study of Enasidenib in IDH2-Mutant Angioimmunoblastic T-Cell Lymphoma
Overview
- Phase
- Phase 2
- Status
- Recruiting
- Enrollment
- 25
- Locations
- 8
- Primary Endpoint
- response rate
Overview
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.
Study Design
- Study Type
- Interventional
- Allocation
- Na
- Intervention Model
- Single Group
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •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.
- •i) See section 6.2 Subject Exclusion Criteria for guidelines regarding adjuvant and maintenance therapy for prior malignancy.
- •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
Exclusion Criteria
- •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
- •Administration of a live vaccine within 6 weeks of first dose of study drug
- •Prior surgery or gastrointestinal condition that may adversely affect drug absorption (e.g.,gastric bypass surgery, gastrectomy)
- •Patients with HIV infection with detectable viral load, CD4 count \<200, or not taking anti-retroviral medications
- •Patients with chronic hepatitis B or C as defined by positive hepatitis B or C serology:
- •Subjects with a negative HBsAg and a positive HBcAb require an undetectable/negative hepatitis B DNA test (e.g., polymerase chain reaction \[PCR\] test) to be enrolled, and will require prophylactic antiviral treatment according to institutional standards of care initiated prior to the first dose of study drug, and continued until approximately 18 months after completion of study drug(s) if rituximab is utilized.
Arms & Interventions
Enasidenib and rituximab
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.
Intervention: Enasidenib (Drug)
Enasidenib and rituximab
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.
Intervention: Rituximab (Drug)
Outcomes
Primary Outcomes
response rate
Time Frame: 1 year
a 20% response rate is undesirable and 45% is desirable
Secondary Outcomes
No secondary outcomes reported