Actively Recruiting
A Pilot Study of Pembrolizumab Combined With Chemotherapy for Newly Diagnosed Primary Central Nervous System Lymphoma
Led by Dana-Farber Cancer Institute · Updated on 2026-02-20
15
Participants Needed
2
Research Sites
26 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 whether combining the investigational drug pembrolizumab with chemotherapy can help treat newly diagnosed primary central nervous system lymphoma (PCNSL) while managing side effects. This open-label pilot trial involves drugs including pembrolizumab, methotrexate, temozolomide, and rituximab. Although pembrolizumab is not FDA-approved for PCNSL, it is approved for other uses, and rituximab is approved for PCNSL. The study involves about 15 participants and is supported by Merck 26 Co.
CONDITIONS
Brief Title
Pembrolizumab + Chemotherapy in Newly Diagnosed PCNSL
Who Can Participate
Eligibility Criteria
You may qualify if you...
- Age 18 years or older
- Pathologically confirmed newly diagnosed primary CNS diffuse large B-cell lymphoma (DLBCL) by brain biopsy, cerebrospinal fluid, or vitreous fluid
- No history or evidence of DLBCL outside the CNS, except treated isolated intraocular lymphoma
- No prior systemic chemotherapy or whole brain radiation therapy for PCNSL
- ECOG performance status 0 to 2 (Karnofsky 270% if related to PCNSL)
- Adequate organ function including neutrophils 1000/bcl, platelets 100,000/bcl, hemoglobin 9.0 g/dL without recent transfusion
- Renal function with creatinine 1.5 x ULN or creatinine clearance 40 mL/min
- Hepatic function within specified bilirubin and liver enzyme limits
- Coagulation parameters within set limits or stable on anticoagulants
- Negative HIV test
- No history of organ transplant or ongoing immunosuppressant therapy
- Women of childbearing potential must have negative pregnancy test before enrollment
- Women not considered of childbearing potential include premenarchal or surgically sterile women
- Women of childbearing potential and men must agree to use effective contraception during and after study treatment
- Able to comply with study requirements
You will not qualify if you...
- Unable to undergo MRI
- Intraocular PCNSL without brain or spinal cord disease
- Receiving any other investigational agents
- History of severe allergic reactions to similar compounds
- Prior therapy with anti-PD-1, anti-PD-L1, anti-PD-L2, or other immune checkpoint agents
- Active autoimmune disease requiring immunosuppressive therapy
- Received live vaccines within 30 days before study drug
- Known progressing malignancy requiring treatment within past 3 years (except certain skin or in situ cancers)
- History of pneumonitis requiring steroids or current pneumonitis
- Poorly controlled diabetes with HbA1c >8%
- Unable to swallow capsules or significant gastrointestinal disease
- Use of enzyme-inducing antiepileptic drugs not discontinued 2 weeks before trial
- Known active hepatitis B or C infection
- Known active tuberculosis
- Immunodeficiency or chronic systemic steroid therapy over 10 mg prednisone equivalent daily
- Prior allogeneic stem cell transplant
- Large pleural effusions, ascites, or full body edema
- Psychiatric or substance abuse disorders interfering with trial participation
- Pregnant, breastfeeding, or planning pregnancy during study period through 120 days after last dose of 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 16 weeks
Participants receive a combination of pembrolizumab, methotrexate, temozolomide, and rituximab in cycles lasting 14 days each, with assessments and imaging at baseline and during cycles 3 and 6.
Multiple visits during 8 cycles of 14 days each, including imaging on cycles 3 and 6
Duration - Approximately 4 to 8 weeks after induction, then up to 15 cycles of 42 days each
Participants who complete induction treatment may receive consolidation therapy consisting of pembrolizumab and lumbar punctures in 42-day cycles, with imaging every other cycle and an end of treatment visit.
Visits every 42 days for up to 15 cycles, including lumbar puncture and imaging every other cycle
Duration - Up to 3 years
Participants are followed up after completion of treatment to monitor safety and treatment outcomes.
Visit schedule varies during follow-up period
Trial Site Locations
Total: 2 locations
1
Brigham and Women's Hospital
Boston, Massachusetts, United States, 02115
Actively Recruiting
2
Dana Farber Cancer Institute
Boston, Massachusetts, United States, 02215
Actively Recruiting
Research Team
L
Lakshmi Nayak, MD
D
DFCI Clinical Trials Hotline
How is the study designed?
Study Type
INTERVENTIONAL
Masking
NONE
Allocation
NON_RANDOMIZED
Model
SEQUENTIAL
Primary Purpose
TREATMENT
Number of Arms
2
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