Primary Central Nervous System LymphomaPhase 2NCT05681195
Zanubrutinib With Pemetrexed to Treat Relapsed/Refractory Primary and Secondary Central Nervous System (CNS) Lymphomas
A Phase 2 study testing Pemetrexed, Zanubrutinib and Autologous Stem Cell Transplant (ASCT) in people with Primary Central Nervous System Lymphoma and Secondary Central Nervous System Lymphoma, run by Baptist Health South Florida at 1 site in United States.
Trial summary
This study is being conducted to evaluate the safety and efficacy of the combination of pemetrexed and zanubrutinib (called induction therapy) followed by zanubrutinib treatment alone (also called maintenance therapy) in people who have relapsed or refractory (RR) primary central nervous system lymphoma (PCNSL) or… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Primary Central Nervous System Lymphoma, Secondary Central Nervous System Lymphoma, Relapsed Cancer
- What is being tested?
- Pemetrexed, Zanubrutinib and Autologous Stem Cell Transplant (ASCT)
- Type of treatment
- Pill or oral medicine, Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 15 participants
- Where
- 1 siteUnited States
- Study dates
- 25 Apr 2024to Feb 2033
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Any of the following diseases histologically confirmed:
- Primary CNS lymphoma or isolated secondary CNS involvement by diffuse large B cell lymphoma with measurable disease
- Cytologic diagnosis of B cell non-Hodgkin's lymphoma with measurable disease
- Ocular lymphoma with histologic confirmation of ocular lymphoma and measurable intracranial tumor. Slit-lamp examination and vitreal or retinal biopsy will be done to confirm ocular lymphoma.
- Karnofsky performance status (KPS) ≥ 30% (≥ 50% for patients ≥ 60 years-old)
- Progressed during first-line chemotherapy and/or radiotherapy -OR- insufficient clinical response to previous therapy or relapsed after initial successful treatment OR unable to tolerate previous therapy defined as Grade 3+ acute kidney injury (AKI) and/or transaminase elevation according to CTCAE v 5.0 criteria preventing repeat treatment exposure OR prior glucarpidase use due to high dose methotrexate delayed clearance and/or toxicity OR those who would have been glucarpidase candidates due to delayed methotrexate clearance (plasma methotrexate concentrations greater than 2 standard deviations of the mean methotrexate excretion curve specific for the dose of methotrexate administered or toxic plasma methotrexate concentrations (>1 micromole per liter) in patients with delayed methotrexate clearance) due to impaired renal function OR unable to receive high dose methotrexate induction on every 2 week +/- 3 days schedule due to deconditioning and/OR need for physical rehabilitation between the high dose methotrexate treatments
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- No systemic lymphoma by positron emission tomography (PET) CT or CT scan of the chest, abdomen, and pelvis with contrast
- Adequate bone marrow and organ function demonstrated by:
- Absolute neutrophil count (ANC) ≥ 1.5 x 10^9/L
- Platelets ≥ 75 x 10^9/L and no platelet transfusion within the past 14 days prior to study enrollment
- Hemoglobin (Hgb) ≥ 8 g/dL and no red blood cell (RBC) transfusion within the past 14 days prior to study enrollment
- Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 3 times the upper limit of normal
- Serum bilirubin ≤ 1.5 times the upper limit of normal; or total bilirubin ≤ 3 times the upper limit of normal with direct bilirubin within the normal range in patients with well documented Gilbert Syndrome
- Creatinine Clearance (CrCl)> 45 mL/minute using Cockcroft-Gault formula
- Ability to understand and sign written informed consent prior to study entry unless the subject suffers from cognitive or physical impairment due to their CNS malignancy or due to a known underlying medical condition in which case consent could be signed by proxy
- Life expectancy of at least 2 months
- Females of childbearing potential must use highly effective method of contraception for the duration of the study and ≥ 30 days after the last dose of zanubrutinib. Female must also have a negative urine or serum pregnancy test ≤ 7 days before initial treatment.
- The investigator or a designated associate is requested to advise the patients how to achieve highly effective birth control (failure rate of less than 1%), e.g., intrauterine device (IUD), intrauterine hormone-releasing system (IUS), bilateral tubal occlusion, vasectomized partner and sexual abstinence. Females using hormonal contraception should use barrier methods in addition.
- Male patients with a female partner of childbearing potential are eligible if abstinent, vasectomized, or if they agree to the use of barrier contraception with other methods described above during the study treatment period and for up to one week after the last dose of zanubrutinib.
- Agreement to use contraception during study participation
- Female patients of childbearing potential must practice highly effective methods of contraception.
- Male patients with female partners must be abstinent, vasectomized, or agree to the use of barrier contraception in combination with other methods. Acceptable contraception methods are included in the study protocol.
- Patients using hormonal contraceptives (e.g., birth control pills or devices) must use a barrier method of contraception (e.g., condoms) as well.
- For patients with Infectious disease, must have:
- HIV positive with negative viral load and CD4 count > 400
- Non-viremic Hepatitis C Virus (HCV)
- HBcAb (Hepatitis B core positive) and HBsAg negative
Who cannot join
- Serious uncontrolled concurrent illness or comorbid condition
- Other active systemic malignancy except for basal cell carcinoma of the skin, cervical carcinoma in situ or very low and low risk prostate cancer under observation. Patients with a remote history (3 years or more) of malignancy are eligible for the protocol in the absence of active disease
- Concurrent chronic systemic immune therapy, targeted therapy not indicated in this study protocol
- Unable to comprehend the study requirements or who are not likely to comply with the study protocol
- Prior participation in chemotherapy, cytotoxic therapy, immunotherapy, radiation therapy or therapeutic protocols within 2 weeks of protocol treatment
- Pregnant (confirmed by serum or urine β-HCG) or lactating
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- Transaminases > 3 times above the upper limits of the institutional normal
- Patients must not have pre-existing immunosuppression, concurrent immunosuppressive treatment with the exception of dexamethasone, or low dose prednisone with a total dose equivalent to 15 mg of prednisone a day or less for chronic conditions. Allogeneic stem cell transplant recipients as well as other organ transplant recipients are excluded. Autologous stem cell transplant recipients will qualify if relapse occurs at one year after the stem cell transplantation. Short course of dexamethasone up to 40 mg orally or intravenously daily with or without taper for CNS lymphoma symptom control is allowed.
- Patients should not have active and/or ongoing autoimmune anemia and/or autoimmune thrombocytopenia (e.g., idiopathic thrombocytopenia purpura).
- Non-healing wound, ulcer or bone fracture
- Known bleeding diathesis (e.g., von Willebrand's disease) or hemophilia
- Cerebrovascular accident or intracranial hemorrhage within 6 months of the study treatment; arterial or venous thrombotic or embolic event such as deep vein thrombosis or pulmonary embolism within 3 months before the start of study treatment. Patients with upper extremity catheter-related deep venous thrombosis will not be excluded.
- Concurrent use of warfarin or other vitamin K antagonists (need to be stopped 7 days prior to starting on trial drug)
- Infectious disease: HIV positive patients with positive viral load and CD4+ count < 400 are excluded. HIV patients must have established and consistent infectious disease specialist care. HIV positive patients have to agree for every 12-week monitoring of viral load. Patients with the emergence of HIV viral load on the trial treatment will be referred to the infectious disease specialist and can continue on the trial treatment unless recommended to stop by the infectious disease specialist and PI. If the viral load reaches 100,000 copies per milliliter or above, the patient would be referred to an infectious disease specialist for and evaluation and would be taken off the trial.
- Patients with presence of HCV antibody are eligible if HCV RNA is undetectable and if they are willing to undergo monitoring for HCV reactivation every 12 weeks. HCV patients will be taken off trial if there is 1 log increase in viral load after the initial detection of HCV viral load regardless of liver function tests (LFTs). Patients will be referred promptly to hepatology specialist with the first detectable viral load.
- Patients with detectable hepatitis B surface antigen (HBsAg) are excluded. Patients with viral hepatitis B core antibody (HBcAb) positivity, but absence of HBsAg, are eligible if HBV DNA is undetectable and if they are willing to undergo monitoring for Hepatitis B Virus (HBV) reactivation every 12 weeks. HBV patients will be taken off trial if there is 1 log increase in viral load after the initial detection of HBV viral load regardless of LFTs. Patients will be referred promptly to hepatology specialist with the first detectable viral load.
- Currently active, clinically significant cardiovascular disease including the following:
- Myocardial infarction within 6 months before screening
- Unstable angina within 3 months before screening
- New York Heart Association class III or IV congestive heart failure
- History of clinically significant arrhythmias (e.g., sustained ventricular tachycardia, ventricular fibrillation, torsades de pointes)
- Any uncontrolled active systemic infection or infection requiring systemic treatment that was completed ≤ 7 days before the first dose of therapy
- Participants who received a strong cytochrome P450 (CYP) 3A inhibitor or inducer within 7 days prior to the first dose of protocol anti-fungal prophylaxis, or participants who require continuous treatment with a strong CYP3A inhibitor/inducer (i.e., except for any medication to be specifically mentioned in this protocol)
- Any life-threatening illness, medical condition, or organ system dysfunction that, in the investigator's opinion, could compromise the patient's safety, or put the study at undue risk. Participants with suspicious radiologic evidence of aspergillosis infection (i.e., chest CT and/or brain MRI) will not be eligible unless confirmatory laboratory testing of Beta-D glucan and aspergillus antigen are negative
- Prior treatment with pemetrexed or a Bruton's tyrosine kinase (BTK) inhibitor for lymphoma
- Vaccination with a live or attenuates vaccine within 28 days prior to the first dose of zanubrutinib. Live or attenuated vaccines are not allowed during treatment with zanubrutinib
- Hypersensitivity to zanubrutinib or pemetrexed or any of the other ingredients of the applicable study drug
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
Miami Cancer Institute at Baptist Health, Inc.
Miami, Florida, 33176
Yuliya Linhares, M.D., 786-596-2000, yuliyal@baptisthealth.net
About this study
Official title: Zanubrutinib With Pemetrexed for the Treatment of Relapsed/Refractory Primary and Secondary CNS Lymphomas: A Phase II Trial With a Safety Lead-In
This study is being conducted to evaluate the safety and efficacy of the combination of pemetrexed and zanubrutinib (called induction therapy) followed by zanubrutinib treatment alone (also called maintenance therapy) in people who have relapsed or refractory (RR) primary central nervous system lymphoma (PCNSL) or isolated central nervous system relapse of B cell lymphoma (SCNSL). Assessments include how well people respond to this treatment, whether their disease gets better or worse, and their survival. Safety of this treatment and its side effects also will be assessed.
Read the detailed description
Pemetrexed, when used by itself, is beneficial and is a standard of care therapy for RR PCNSL and can be used to treat SCNSL. Zanubrutinib is an oral drug that is approved by the Food and Drug Administration (FDA) as safe and effective to treat certain lymphoma types.
- Conditions
- Primary Central Nervous System Lymphoma, Secondary Central Nervous System Lymphoma, Relapsed Cancer, Refractory Cancer
- Being tested
- Pemetrexed, Zanubrutinib, Autologous Stem Cell Transplant (ASCT), Whole Brain Radiation Therapy (WBRT)
- Medical subject headings
- Recurrence, Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PemetrexedDrug
Also called Alimta
Participants will receive 900 mg/m^2 via IV infusion over 10 minutes every 3 weeks x 4-8 induction cycles (21 days per cycle) as part of the induction therapy.
ZanubrutinibDrug
Also called Brukinsa
Participants will receive 320 mg PO daily or dose-adjusted when given concomitantly with CYP3A4 inhibitor on Days 3-19 of each induction cycle x 4-8 cycles (21 days per cycle) as part of the induction therapy.
For those on maintenance therapy, participants will receive 320 mg PO daily or dose-adjusted when given concomitantly with CYP3A4 inhibitor on Days 1-28 of each maintenance cycle (28 days per cycle) until the transplant (if applicable) or disease progression.
Autologous Stem Cell Transplant (ASCT)Procedure or surgery
ASCT will occur in participants who are candidates for this procedure according to standard of care institutional protocols
Whole Brain Radiation Therapy (WBRT)Radiation
WBRT will occur in participants who are candidates for this procedure but not candidates for ASCT according to standard of care institutional protocols
| Study group | Role | What they receive |
|---|---|---|
| Induction Therapy + SOC Treatment | Experimental | Participants will receive the induction therapy (oral zanubrutinib + IV pemetrexed) and be placed into one of the cohorts according to standard of care (SOC) treatment:
Cohort 1: Induction Therapy + Autologous Stem Cell Transplant (ASCT) After completion of the induction therapy, ASCT candidates will undergo transplant as per SOC. If the transplant is delayed and 8 induction cycles have been completed, oral zanubrutinib maintenance will proceed until transplant, but will not occur after transplant.
Cohort 2: Induction Therapy + Whole Brain Radiation Therapy (WBRT) After completion of the induction therapy, WBRT candidates will undergo WBRT as per SOC. Oral zanubrutinib maintenance will start 7-10 days after the completion of WBRT. 28-d maintenance cycles will continue until disease progression.
Cohort 3: Induction Therapy Alone After completion of the induction therapy, 28-day oral zanubrutinib maintenance cycles will begin and continue until disease progression Receives: Drug: Pemetrexed; Drug: Zanubrutinib; Procedure: Autologous Stem Cell Transplant (ASCT); Radiation: Whole Brain Radiation Therapy (WBRT) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Best Overall Response Rate (ORR) to Induction Therapy
Best ORR to induction therapy is defined as the best response between the start of induction therapy until the end of induction therapy based on the criteria set forth in "Report of an international workshop to standardize baseline evaluation and response criteria for primary CNS lymphoma" (2005).
Measured: 6 months
Secondary outcomes (10)
Best Overall Response Rate (ORR) after transplant, WBRT + zanubrutinib maintenance, or zanubrutinib maintenance alone
Best ORR is defined as the best response between the transplant and end of study, WBRT and end of study, or start of maintenance therapy and end of study. Response is based on the criteria set forth in "Report of an international workshop to standardize baseline evaluation and response criteria for primary CNS lymphoma" (2005).
Measured: 5 years
Complete Response (CR) Rate to induction therapy
Rate of CR to induction therapy is defined as the number of participants out of the total who demonstrate CR between the start of induction therapy until the end of induction therapy based on the criteria set forth in "Report of an international workshop to standardize baseline evaluation and response criteria for primary CNS lymphoma" (2005). CR includes confirmed and unconfirmed CR (CRu). CRu is defined as any participant who fulfills all criteria for CR but continues to require corticosteroid therapy or have a small but persistent enhancing abnormality on MRI related to biopsy or focal hemorrhage
Measured: 6 months
Complete Response (CR) Rate after transplant, WBRT + zanubrutinib maintenance, or zanubrutinib maintenance alone
Rate of CR to is defined as the number of participants out of the total who demonstrate CR between the transplant and end of study, WBRT and end of study, or start of maintenance therapy and end of study. Response is based on the criteria set forth in "Report of an international workshop to standardize baseline evaluation and response criteria for primary CNS lymphoma" (2005). CR includes confirmed and unconfirmed CR (CRu). CRu is defined as any participant who fulfills all criteria for CR but continues to require corticosteroid therapy or have a small but persistent enhancing abnormality on MRI related to biopsy or focal hemorrhage.
Measured: 5 years
Duration of Response (DOR)
DOR is defined as the duration of time from when complete or partial response is first identified to the time when progression is identified. Response is based on the criteria set forth in "Report of an international workshop to standardize baseline evaluation and response criteria for primary CNS lymphoma" (2005).
Measured: 5 years
Duration of Complete Response (DOCR)
DOCR is defined as the duration of time from when complete response is first identified to the time when partial response or progression is identified. Response is based on the criteria set forth in "Report of an international workshop to standardize baseline evaluation and response criteria for primary CNS lymphoma" (2005).
Measured: 5 years
Change in Progression-Free Survival (PFS)
PFS is defined as time from start of induction therapy to the time when progression is identified or the participant expires, whichever comes first.
Measured: 1 year and 5 years
Change in Overall Survival (OS)
OS is defined as time from start of induction therapy to the time when a participant expires.
Measured: 2 years and 5 years
Frequency of Dose-Limiting Toxicities (DLTs)
A DLT will be defined as the occurrence of any of the following adverse events at least possibly related to the study medication during the DLT review period. The DLT review period will be defined during the first three 21-day cycles of zanubrutinib-pemetrexed combination treatment. Adverse events unrelated to study drugs will not be considered DLTs.
Measured: 9 weeks
Clinical benefit rate to induction therapy (pre-transplant, WBRT or zanubrutinib maintenance)
To assess the clinical benefit (CR, CRu, PR, SD) rate to induction therapy (pre-transplant, WBRT or zanubrutinib maintenance). Response is based on the criteria set forth in "Report of an international workshop to standardize baseline evaluation and response criteria for primary CNS lymphoma" (2005). CR includes confirmed and unconfirmed CR (CRu). CRu is defined as any participant who fulfills all criteria for CR but continues to require corticosteroid therapy or have a small but persistent enhancing abnormality on MRI related to biopsy or focal hemorrhage.
Measured: 6 months
Clinical benefit rate post-transplant, WBRT followed by zanubrutinib maintenance or zanubrutinib maintenance)
To assess the clinical benefit (CR, CRu, PR, SD) rate post-transplant, WBRT followed by zanubrutinib maintenance or zanubrutinib maintenance; subgroup analysis will be performed on the participants who have not received WBRT. Response is based on the criteria set forth in "Report of an international workshop to standardize baseline evaluation and response criteria for primary CNS lymphoma" (2005). CR includes confirmed and unconfirmed CR (CRu). CRu is defined as any participant who fulfills all criteria for CR but continues to require corticosteroid therapy or have a small but persistent enhancing abnormality on MRI related to biopsy or focal hemorrhage.
Measured: 5 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Jan 2023
- Study start25 Apr 2024
- Primary completionFeb 2028 (estimated)
- Study completionFeb 2033 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Primary Central Nervous System LymphomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 15 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Baptist Health South Florida
- Sponsor type
- University, hospital or other
- Collaborators
- BeiGene
- Responsible party
- Sponsor
- Investigators
- Yuliya Linhares, M.D., Principal investigator, Miami Cancer Institute at Baptist Health, Inc.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05681195
- Sponsor's protocol ID
- 2021-LIN-001
- Status last verified
- Mar 2026
- First submitted
- 8 Dec 2022
- Last updated
- 3 Mar 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 3 Mar 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Zanubrutinib With Pemetrexed for the Treatment of Relapsed/Refractory Primary and Secondary CNS Lymphomas: A Phase II Trial With a Safety Lead-In
- ClinicalTrials.gov ID
- NCT05681195
- Acronym / sponsor ID
- 2021-LIN-001
- Conditions
- Primary Central Nervous System Lymphoma, Secondary Central Nervous System Lymphoma, Relapsed Cancer, Refractory Cancer
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 15 participants (estimated)
- Lead sponsor
- Baptist Health South FloridaUniversity, hospital or other
- Collaborators
- BeiGene
- Study start
- 25 Apr 2024 (actual)
- Primary completion
- Feb 2028 (estimated)
- Study completion
- Feb 2033 (estimated)
- First posted
- 12 Jan 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study is being conducted to evaluate the safety and efficacy of the combination of pemetrexed and zanubrutinib (called induction therapy) followed by zanubrutinib treatment alone (also called maintenance therapy) in people who have relapsed or refractory (RR) primary central nervous system lymphoma (PCNSL) or isolated central nervous system relapse of B cell lymphoma (SCNSL). Assessments include how well people respond to this treatment, whether their disease gets better or worse, and their survival. Safety of this treatment and its side effects also will be assessed.
Detailed description
Pemetrexed, when used by itself, is beneficial and is a standard of care therapy for RR PCNSL and can be used to treat SCNSL. Zanubrutinib is an oral drug that is approved by the Food and Drug Administration (FDA) as safe and effective to treat certain lymphoma types.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Induction Therapy + SOC Treatment | Experimental | Drug: Pemetrexed, Drug: Zanubrutinib, Procedure: Autologous Stem Cell Transplant (ASCT), Radiation: Whole Brain Radiation Therapy (WBRT)Participants will receive the induction therapy (oral zanubrutinib + IV pemetrexed) and be placed into one of the cohorts according to standard of care (SOC) treatment: Cohort 1: Induction Therapy + Autologous Stem Cell Transplant (ASCT) After completion of the induction therapy, ASCT candidates will undergo transplant as per SOC. If the transplant is delayed and 8 induction cycles have been completed, oral zanubrutinib maintenance will proceed until transplant, but will not occur after transplant. Cohort 2: Induction Therapy + Whole Brain Radiation Therapy (WBRT) After completion of the induction therapy, WBRT candidates will undergo WBRT as per SOC. Oral zanubrutinib maintenance will start 7-10 days after the completion of WBRT. 28-d maintenance cycles will continue until disease progression. Cohort 3: Induction Therapy Alone After completion of the induction therapy, 28-day oral zanubrutinib maintenance cycles will begin and continue until disease progression |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (27 listed)
- Any of the following diseases histologically confirmed:
- Karnofsky performance status (KPS) ≥ 30% (≥ 50% for patients ≥ 60 years-old)
- Progressed during first-line chemotherapy and/or radiotherapy -OR- insufficient clinical response to previous therapy or relapsed after initial successful treatment OR unable to tolerate previous therapy defined as Grade 3+ acute kidney injury (AKI) and/or transaminase elevation according to CTCAE v 5.0 criteria preventing repeat treatment exposure OR prior glucarpidase use due to high dose methotrexate delayed clearance and/or toxicity OR those who would have been glucarpidase candidates due to delayed methotrexate clearance (plasma methotrexate concentrations greater than 2 standard deviations of the mean methotrexate excretion curve specific for the dose of methotrexate administered or toxic plasma methotrexate concentrations (>1 micromole per liter) in patients with delayed methotrexate clearance) due to impaired renal function OR unable to receive high dose methotrexate induction on every 2 week +/- 3 days schedule due to deconditioning and/OR need for physical rehabilitation between the high dose methotrexate treatments
- No systemic lymphoma by positron emission tomography (PET) CT or CT scan of the chest, abdomen, and pelvis with contrast
- Adequate bone marrow and organ function demonstrated by:
Key exclusion criteria (27 listed)
- Serious uncontrolled concurrent illness or comorbid condition
- Other active systemic malignancy except for basal cell carcinoma of the skin, cervical carcinoma in situ or very low and low risk prostate cancer under observation. Patients with a remote history (3 years or more) of malignancy are eligible for the protocol in the absence of active disease
- Concurrent chronic systemic immune therapy, targeted therapy not indicated in this study protocol
- Unable to comprehend the study requirements or who are not likely to comply with the study protocol
- Prior participation in chemotherapy, cytotoxic therapy, immunotherapy, radiation therapy or therapeutic protocols within 2 weeks of protocol treatment
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| PemetrexedAlso: AlimtaParticipants will receive 900 mg/m^2 via IV infusion over 10 minutes every 3 weeks x 4-8 induction cycles (21 days per cycle) as part of the induction therapy. | Drug | Induction Therapy + SOC Treatment |
| ZanubrutinibAlso: BrukinsaParticipants will receive 320 mg PO daily or dose-adjusted when given concomitantly with CYP3A4 inhibitor on Days 3-19 of each induction cycle x 4-8 cycles (21 days per cycle) as part of the induction therapy. For those on maintenance therapy, participants will receive 320 mg PO daily or dose-adjusted when given concomitantly with CYP3A4 inhibitor on Days 1-28 of each maintenance cycle (28 days per cycle) until the transplant (if applicable) or disease progression. | Drug | Induction Therapy + SOC Treatment |
| Autologous Stem Cell Transplant (ASCT)ASCT will occur in participants who are candidates for this procedure according to standard of care institutional protocols | Procedure or surgery | Induction Therapy + SOC Treatment |
| Whole Brain Radiation Therapy (WBRT)WBRT will occur in participants who are candidates for this procedure but not candidates for ASCT according to standard of care institutional protocols | Radiation | Induction Therapy + SOC Treatment |
Primary outcome
Best Overall Response Rate (ORR) to Induction Therapy
Time frame: 6 months
Best ORR to induction therapy is defined as the best response between the start of induction therapy until the end of induction therapy based on the criteria set forth in "Report of an international workshop to standardize baseline evaluation and response criteria for primary CNS lymphoma" (2005).
10 secondary outcomes
Best Overall Response Rate (ORR) after transplant, WBRT + zanubrutinib maintenance, or zanubrutinib maintenance alone
Time frame: 5 years
Complete Response (CR) Rate to induction therapy
Time frame: 6 months
Complete Response (CR) Rate after transplant, WBRT + zanubrutinib maintenance, or zanubrutinib maintenance alone
Time frame: 5 years
Duration of Response (DOR)
Time frame: 5 years
Duration of Complete Response (DOCR)
Time frame: 5 years
Change in Progression-Free Survival (PFS)
Time frame: 1 year and 5 years
Change in Overall Survival (OS)
Time frame: 2 years and 5 years
Frequency of Dose-Limiting Toxicities (DLTs)
Time frame: 9 weeks
Clinical benefit rate to induction therapy (pre-transplant, WBRT or zanubrutinib maintenance)
Time frame: 6 months
Clinical benefit rate post-transplant, WBRT followed by zanubrutinib maintenance or zanubrutinib maintenance)
Time frame: 5 years
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Mar 2026.
- Miami Cancer Institute at Baptist Health, Inc.Link provided by the sponsor.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Yuliya Linhares, M.D. principal investigator
Miami Cancer Institute at Baptist Health, Inc.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Pemetrexed, Zanubrutinib and Autologous Stem Cell Transplant (ASCT) in people with Primary Central Nervous System Lymphoma and Secondary Central Nervous System Lymphoma, run by Baptist Health South Florida at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 27 inclusion and 27 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 3 Mar 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Yuliya Linhares, M.D. ((786) 596-2000, YuliyaL@baptisthealth.net), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Best Overall Response Rate (ORR) to Induction Therapy (time frame: 6 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Mar 2026.