Pembrolizumab, Ibrutinib and Rituximab in PCNSL

Recruiting now · Phase 1/Phase 2

Conditions studied: Primary Central Nervous System Lymphoma, Recurrent Cancer, Refractory Cancer, Relapsed Cancer

In brief

This research study is evaluating a combination therapy of 3 drugs as possible treatments for recurrent primary central nervous system lymphoma (PCNSL). The three drugs being used in the study are: * Pembrolizumab (MK3475) * Ibrutinib * Rituximab (or biosimilar)

Key facts

Study ID

NCT04421560

Run by

Dana-Farber Cancer Institute

People needed

37

Starts

2020-08-01

Expected to finish

2027-01-05

Last updated by the study team

2026-02-20

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• Participant must be able to understand and willing to sign a written informed consent document.
• Participant must have signed and dated an IRB/IEC approved written informed consent form in accordance with regulatory and institutional guidelines. This must be obtained before the performance of any protocol-related procedures that are not part of normal subject care.
• Participant must be willing and able to comply with scheduled visits, treatment schedule, laboratory tests, and other requirements of the study.
• Participant must be at least 18 years old on day of signing informed consent.
• Subjects with pathologically confirmed PCNSL who progressed after CNS-directed therapy, primary refractory disease and relapsed disease are allowed. Participants should have evidence of R/R disease on MRI or CSF cytology. Ocular only recurrences are allowed.
• Subjects must have a Eastern Cooperative Oncology Group (ECOG) performance status of 0-1.
• Life expectancy of >3 months (in the opinion of the investigator)
• Toxicities due to prior therapy must be stable and recovered to ≤ Grade 1
• Must be able to tolerate lumbar puncture and/or Ommaya taps
• Demonstrate adequate organ function as defined below, all screening labs should be performed within 28 days of treatment initiation.
• Hematology
• White Blood Count (WBC) ≥ 2 K/μL
• Platelet count ≥ 100 K/μL
• Absolute Neutrophil Count ≥ 1.5 K/μL
• Hemoglobin > 9.0 g/dL or ≥ 5.6 mmol/L (Criteria must be met without erythropoietin dependency and without packed red blood cell (pRBC) transfusion within last 2 weeks)
• Biochemistry
• Serum creatinine ≤1.5 x institutional ULN OR Measured or calculated creatinine clearance ≥30 mL/min for participant with creatinine levels >1.5 × institutional ULN (Creatinine clearance should be calculated per institutional standard)
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 x ULN(≤5 × ULN for participants with liver metastases)
• Total bilirubin (TBILI) ≤ 1.5 x institutional ULN (except subjects with Gilbert Syndrome who must have a total bilirubin level of < 3.0 x institutional ULN) OR Direct bilirubin ≤ULN for participants with total bilirubin levels >1.5 × ULN)
• Coagulation studies
• INR OR PT and Activated aPTT ≤1.5 × institutional ULN unless participant is receiving anticoagulant therapy as long as PT or aPTT is within therapeutic range of intended use of anticoagulants
• Women of child-bearing potential (WOCBP), defined as all women physiologically capable of becoming pregnant, must have a negative serum pregnancy test within 72 hours prior to registration.
• Women in the following categories are not considered WOCBP:
• Premenarchal
• Premenopausal female with 1 of the following:

You may not qualify if…

• Participants who meet any of the following criteria will not be eligible for admission into the study.
• Patients who cannot undergo MRI brain
• Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (eg, CTLA-4, OX-40,CD137)
• Previously progressed on ibrutinib or other BTK inhibitor use (patient who have previously received BTK inhibitor but not progressed while on it are allowed)
• Patients with > Grade 2 intracranial hemorrhage
• Concomitant warfarin, any other warfarin-derivative anticoagulant, vitamin K antagonists, within 7 days before starting treatment. Note: novel oral anticoagulants (NOACs, e.g., Apixaban, Dabigatran, Edoxaban, Rivaroxaban), low molecular weight heparin (LMWH) are allowed
• Arterial thromboembolic events such as cerebrovascular accident within 3 months before the start of study treatment
• Active autoimmune disease requiring immunosuppressive agents or steroids (prednisone >10mg or equivalent)
• Has active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs).Replacement therapy (eg., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment
• Requires treatment for PCNSL with high dose systemic corticosteroids defined as dexamethasone > 4 mg/day or bioequivalent for >3 consecutive days within 2 weeks of registration
• Has received prior systemic anti-cancer therapy including investigational agents within 4 weeks [could consider shorter interval for kinase inhibitors or other short half-life drugs] prior to dosing. OR 5 half-lives, whichever is shorter --- Note: Participants must have recovered from all AEs due to previous therapies to ≤Grade 1 or baseline. Participants with≤Grade 2 neuropathy may be eligible.
• Patients who underwent major surgery ≤ 2 weeks before starting study treatment are excluded. If participant underwent major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting study treatment. Patients who plan to undergo surgery within 2 weeks of first dose of study treatment are excluded.
• Participants must have recovered from all radiation-related toxicities, not require corticosteroids, and not have had radiation pneumonitis. A 1-week washout is permitted for palliative radiation (≤2 weeks of radiotherapy) to non-CNS disease. Has received prior radiotherapy to CNS disease within 2 weeks of start of study treatment.
• Has received a live vaccine within 30 days prior to the first dose of study drug. Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella,varicella/zoster (chicken pox), yellow fever, rabies, Bacillus Calmette-Guérin (BCG), and typhoid vaccine. Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines (eg, FluMist®) are live attenuated vaccines and are not allowed.
• Has a known additional malignancy that is progressing or has required active treatment within the past 3 years. Note: Participants with basal cell carcinoma of the skin, squamous cell carcinoma of the skin, transitional cell carcinoma of urothelial cancer, or carcinoma in situ (e.g. breast carcinoma, cervical cancer in situ) that have undergone potentially curative therapy are not excluded.
• Has severe hypersensitivity (≥ Grade 3) to study agents and/or any of its excipients.
• Has a history of (non-infectious) pneumonitis that required steroids or has current pneumonitis.
• Patient is known to have an uncontrolled active systemic infection (>CTCAE grade 2) and recent infection requiring intravenous anti-infective treatment that was completed ≤14 days before the first dose of study drug.
• Clinically significant cardiovascular disease such as uncontrolled or symptomatic arrhythmias, congestive heart failure (New York Heart Association > Class 2), unstable angina, or myocardial infarction within 6 months of screening, or any Class 3 or 4 cardiac disease as defined by the New York Heart Association Functional Classification
• Uncontrolled hypertension despite optimal medical management (per investigator's assessment).
• Patient has poorly controlled diabetes mellitus with a glycosylated hemoglobin >8% or poorly controlled steroid-induced diabetes mellitus with a glycosylated hemoglobin of >8%.
• Non-healing wound, ulcer or bone fracture.
• Known bleeding diathesis (eg, von Willebrand's disease) or hemophilia.
• Unable to swallow capsules or disease significantly affecting gastrointestinal function, such as malabsorption syndrome, resection of the stomach or small bowel, or complete bowel obstruction.
• Concurrent administration of medications or foods that are moderate or strong inhibitors or strong inducers of cytochrome P450 (CYP) 3A4/5 (need to be discontinued 2 weeks before starting study treatment)

Where it is running

• Dana Farber Cancer Institute — Boston, Massachusetts, United States (enrolling)
• Beth Israel Deaconess Medical Center — Boston, Massachusetts, United States (enrolling)
• Memorial Sloan Kettering Cancer Center — New York, New York, United States (enrolling)
• Columbia University Medical Center — New York, New York, United States

Full record on ClinicalTrials.gov

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