Actively Recruiting
Zanubrutinib With Pemetrexed for Relapsed/Refractory Primary and Secondary CNS Lymphomas: Phase II Trial With Safety Lead-In
Led by Baptist Health South Florida · Updated on 2026-03-03
15
Participants Needed
1
Research Sites
261 weeks
Total Duration
On this page
Sponsors
B
Baptist Health South Florida
Lead Sponsor
B
BeiGene
Collaborating Sponsor
AI-Summary
What this Trial Is About
This research aims to evaluate the safety and effectiveness of combining pemetrexed and zanubrutinib as induction therapy, followed by zanubrutinib alone as maintenance therapy, in adults with relapsed or refractory primary central nervous system lymphoma (PCNSL) or isolated central nervous system relapse of B cell lymphoma (SCNSL). The study observes how well patients respond, whether their disease improves or worsens, and their survival rates while monitoring safety and side effects. Participants receive induction therapy that includes oral zanubrutinib and intravenous pemetrexed over 4 to 8 cycles. After induction, participants are grouped into three cohorts based on standard care: one undergoes autologous stem cell transplant (ASCT), another receives whole brain radiation therapy (WBRT) followed by zanubrutinib maintenance, and the last continues with zanubrutinib maintenance alone until disease progression. Throughout the study, participants undergo assessments of their response to treatment, including best overall response rates and complete response rates at various points, lasting up to 5 years. Researchers also monitor progression-free survival, overall survival, and any dose-limiting toxicities. Safety is closely tracked, and participants are followed regularly for up to five years to evaluate long-term outcomes and benefits of the treatment regimen.
CONDITIONS
Brief Title
Zanubrutinib With Pemetrexed to Treat Relapsed/Refractory Primary and Secondary Central Nervous System (CNS) Lymphomas
Who Can Participate
Eligibility Criteria
You may qualify if you...
- Histologically confirmed primary CNS lymphoma or isolated secondary CNS involvement by diffuse large B cell lymphoma with measurable disease
- Karnofsky performance status (KPS) of 30% or higher (50% or higher if age 60 or older)
- Disease progressed during first-line therapy, insufficient response to previous treatment, relapsed after initial treatment, or unable to tolerate previous therapy
- No systemic lymphoma detected by PET CT or CT scans
- Adequate bone marrow and organ function including ANC ≥ 1.5 x 10^9/L, platelets ≥ 75 x 10^9/L, hemoglobin ≥ 8 g/dL, liver enzymes ≤ 3 times upper limit, bilirubin ≤ 1.5 times upper limit (or up to 3 times with normal direct bilirubin in Gilbert Syndrome), creatinine clearance > 45 mL/min
- Ability to understand and sign informed consent or have consent signed by proxy if unable
- Life expectancy of at least 2 months
- Females of childbearing potential must use highly effective contraception during and 30 days after treatment and have a negative pregnancy test
- Agreement to use contraception for both female and male participants with partners of childbearing potential
- Patients with HIV, non-viremic Hepatitis C, or HBcAb positive and HBsAg negative, meeting specific viral load and monitoring criteria
You will not qualify if you...
- Serious uncontrolled illness or comorbid condition
- Other active systemic malignancy except certain low-risk cancers or those in remission for 3+ years
- Concurrent chronic systemic immune or targeted therapy not part of this study
- Inability to comply with study requirements
- Recent chemotherapy, immunotherapy, or radiation within 2 weeks prior to treatment
- Pregnant or lactating women
- Liver transaminases more than 3 times normal
- Pre-existing immunosuppression or current immunosuppressive treatment above study limits
- Active autoimmune anemia or thrombocytopenia
- Non-healing wounds, ulcers, or bone fractures
- Known bleeding disorders
- Recent stroke or significant clotting events within specified timeframes
- Use of warfarin or certain blood thinners not stopped 7 days before trial
- HIV patients with positive viral load or low CD4 count
- Detectable hepatitis B surface antigen
- Significant cardiovascular disease
- Active infections requiring treatment within 7 days before therapy
- Recent use or need for strong CYP3A inhibitors or inducers
- Life-threatening illness or organ dysfunction risking safety
- Previous treatment with pemetrexed or Bruton's tyrosine kinase inhibitors for lymphoma
- Recent vaccination with live or attenuated vaccines
- Allergy or hypersensitivity to study drugs or their ingredients
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 - 12 to 24 weeks (4 to 8 cycles, 21 days per cycle)
Participants receive induction therapy consisting of intravenous pemetrexed every 3 weeks for 4 to 8 cycles and oral zanubrutinib daily on specified days of each cycle.
Up to 8 visits every 3 weeks for infusions and assessments
Duration - Varies depending on cohort
Participants are placed into one of three cohorts after induction therapy: those undergoing autologous stem cell transplant, those receiving whole brain radiation therapy, or those continuing with zanubrutinib maintenance alone.
Visits vary depending on cohort and treatment received
Duration - Until transplant or disease progression (variable length)
Participants receive oral zanubrutinib maintenance cycles every 28 days continuing until transplant, disease progression, or as per standard care depending on cohort assignment.
Monthly visits for zanubrutinib maintenance assessments
Trial Site Locations
Total: 1 location
1
Miami Cancer Institute at Baptist Health, Inc.
Miami, Florida, United States, 33176
Actively Recruiting
Research Team
Y
Yuliya Linhares, M.D.
A
Allison Miller
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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