Actively Recruiting
A Phase Ib/II Study of Pembrolizumab, Ibrutinib, and Rituximab in Refractory or Relapsed Primary Central Nervous System Lymphoma
Led by Dana-Farber Cancer Institute · Updated on 2026-02-20
37
Participants Needed
4
Research Sites
4 weeks
Total Duration
On this page
Sponsors
D
Dana-Farber Cancer Institute
Lead Sponsor
M
Merck Sharp & Dohme LLC
Collaborating Sponsor
AI-Summary
What this Trial Is About
Researchers are evaluating a combination of three drugs—Pembrolizumab, Ibrutinib, and Rituximab—as possible treatments for people with recurrent or refractory primary central nervous system lymphoma (PCNSL). This open-label, multi-center Phase Ib/II trial aims to assess the safety and appropriate dosing in Phase Ib, then further study safety and effectiveness in Phase II. These drugs are investigational for PCNSL but approved for other lymphoma types, with Pembrolizumab designed to block tumor growth signals, Ibrutinib targeting proteins that help lymphoma cells survive, and Rituximab supporting the immune system to attack lymphoma cells. During Phase 1b, participants receive escalating doses of Ibrutinib orally twice daily starting at 560 mg, possibly increasing to 840 mg, combined with Pembrolizumab given intravenously every 3 weeks and Rituximab given intravenously once weekly for 4 weeks. In Phase 2, participants receive the established Ibrutinib dose daily, with the same schedules for Pembrolizumab and Rituximab. Treatment continues for up to 2 years unless serious side effects occur or the disease worsens. Participants will undergo screening to confirm eligibility before starting treatment. Throughout the study, researchers will perform regular evaluations including lab tests and imaging to monitor safety and disease status. After completing treatment, participants will be followed every 3 months for life to track progression-free survival at 6 months and other outcomes such as adverse events, response rates, and overall survival. The study is funded by Merck & Co., Inc. and led by the Dana-Farber Cancer Institute.
CONDITIONS
Brief Title
Pembrolizumab, Ibrutinib and Rituximab in PCNSL
Who Can Participate
Eligibility Criteria
You may qualify if you...
- Able to understand and willing to sign informed consent
- At least 18 years old
- Diagnosed with primary central nervous system lymphoma that is refractory, relapsed, or progressed after prior therapy
- Evidence of recurrent or refractory disease on MRI or cerebrospinal fluid cytology
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
- Life expectancy greater than 3 months
- Stable toxicities from prior therapies at grade 1 or less
- Able to tolerate lumbar puncture or Ommaya taps
- Adequate organ function as shown by specific blood and chemistry lab values within 28 days before treatment
- Negative pregnancy test for women of child-bearing potential
- Women of child-bearing potential must agree to use highly effective contraception during treatment and for 120 days after
- Men must agree to use contraception or abstain from penile-vaginal intercourse during treatment and for 120 days after
You will not qualify if you...
- Unable to undergo brain MRI
- Prior treatment with anti-PD-1, anti-PD-L1, anti-PD-L2, or similar immune checkpoint inhibitors
- Previous progression on Ibrutinib or other BTK inhibitors
- Intracranial hemorrhage greater than grade 2
- Use of warfarin or related anticoagulants within 7 days before treatment
- Recent arterial thromboembolic events within 3 months before treatment
- Active autoimmune disease requiring immunosuppressive therapy or steroids above prednisone 10 mg daily
- Systemic corticosteroid treatment above dexamethasone 4 mg daily for more than 3 consecutive days within 2 weeks prior to study
- Recent systemic anti-cancer therapy within 4 weeks before dosing
- Major surgery within 2 weeks before starting study treatment
- Recent radiation therapy to central nervous system within 2 weeks before treatment
- Live vaccine within 30 days before starting study drug
- Active progressing malignancy requiring treatment within 3 years (except some skin and in situ cancers)
- Severe hypersensitivity to study drugs
- History or current pneumonitis requiring steroids
- Active uncontrolled systemic infection
- Significant cardiovascular disease or uncontrolled hypertension
- Poorly controlled diabetes with high HbA1c
- Non-healing wounds or bleeding disorders
- Unable to swallow capsules or have serious gastrointestinal disease
- Concurrent use of strong CYP3A4/5 inhibitors or inducers
- Use of enzyme-inducing antiepileptic drugs within 2 weeks before starting study drugs
- Known HIV/AIDS, active Hepatitis B or C, or active tuberculosis
- Immunodeficiency or chronic systemic steroid therapy over 10 mg prednisone equivalent daily
- Prior allogeneic stem cell transplant
- Psychiatric or substance abuse disorders interfering with study cooperation
- Pregnancy, breastfeeding, or planning to conceive or father children during study and for 120 days after treatment
AI-Screening
AI-Powered Screening
Complete this quick 3-step screening to check your eligibility
Your Study Journey
Duration - 2 to 4 weeks
Participants are screened for eligibility to participate in the trial.
1 visit (in-person)
Duration - Up to 2 years
Participants receive Pembrolizumab, Ibrutinib, and Rituximab to treat primary central nervous system lymphoma. Treatment continues for up to 2 years as long as there are no serious side effects and the disease does not worsen.
Pembrolizumab given every 3 weeks, Rituximab given once weekly for 4 weeks, Ibrutinib taken daily by mouth
Duration - Lifetime follow-up with visits every 3 months
After treatment ends, participants are followed every 3 months for the rest of their life to monitor their health and disease status.
Visits every 3 months
Trial Site Locations
Total: 4 locations
1
Dana Farber Cancer Institute
Boston, Massachusetts, United States, 02115
Actively Recruiting
2
Beth Israel Deaconess Medical Center
Boston, Massachusetts, United States, 02215
Actively Recruiting
3
Columbia University Medical Center
New York, New York, United States, 10032
Withdrawn
4
Memorial Sloan Kettering Cancer Center
New York, New York, United States, 10065
Actively Recruiting
Research Team
L
Lakshmi Nayak, MD
How is the study designed?
Study Type
INTERVENTIONAL
Masking
NONE
Allocation
NA
Model
SINGLE_GROUP
Primary Purpose
TREATMENT
Number of Arms
1
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