Pembrolizumab + Chemotherapy in Newly Diagnosed PCNSL

Recruiting now · Phase 1

Conditions studied: Lymphoma, Primary Central Nervous System Lymphoma

In brief

This research study is studying if the investigational drug, Pembrolizumab, in combination with chemotherapy helps primary central nervous system lymphoma with acceptable side effects. This research study involves a combination of the below drugs: * Pembrolizumab (a type of monoclonal antibody) * Methotrexate (a type of anti-metabolite) * Temozolomide (a type of alkylating agent) * Rituximab (a type of antibody)

Key facts

Study ID

NCT06475235

Run by

Dana-Farber Cancer Institute

People needed

15

Starts

2024-10-18

Expected to finish

2027-06-30

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…

• Subjects with pathologically confirmed newly diagnosed primary CNS diffuse large B-cell lymphoma (DLBCL) confirmed by one of the following:
• Brain biopsy or resection
• Cerebrospinal fluid
• Vitreous fluid
• Participants must not have any evidence or history of DLBCL outside of the CNS. Participants with prior history of isolated intraocular lymphoma (primary vitreoretinal lymphoma/PVRL) who have received only local therapy are allowed.
• Participants must not have received any systemic chemotherapy or whole brain radiation therapy directed to PCNSL.
• Age ≥18 years.
• ECOG performance status ≤2 (Karnofsky ≥70% will be considered if related to PCNSL, see Appendix A).
• Participants must have adequate organ function as defined below.
• Hematology
• Absolute neutrophil count (ANC) ≥1000/µL
• Platelets ≥100 000/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)
• Renal
• - Creatinine ≤1.5 x ULN OR Measured or calculated creatinine clearance ≥40 mL/min for participant with creatinine levels >1.5 × institutional ULN (Creatinine clearance (CrCl) should be calculated per institutional standard.)
• Hepatic
• Total bilirubin ≤1.5 x ULN OR direct bilirubin ≤ULN for participants with total bilirubin levels >1.5 x ULN
• AST (SGOT) and ALT (SGPT) ≤2.5 × ULN (≤5 × ULN for participants with liver metastases)
• Coagulation
• -International normalized ratio (INR) OR prothrombin time (PT) and activated partial thromboplastin time (aPTT) ≤1.5 × ULN unless participant is receiving anticoagulant therapy as long as PT or aPTT is within therapeutic range of intended use of anticoagulants
• Participants must have negative HIV serology.
• Participants must have no history of organ transplantation or ongoing immunosuppressant therapy.
• Women of child-bearing potential (WOCBP), defined as all women physiologically capable of becoming pregnant, must have a negative serum pregnancy within 72 hours prior to registration.
• Women in the following categories are not considered WOCBP:
• Premenarchal

You may not qualify if…

• Participants who cannot undergo MRI
• Intraocular PCNSL without evidence of brain or spinal cord disease.
• Participants who are receiving any other investigational agents.
• History of allergic reactions or severe hypersensitivity reactions (≥grade 3) attributed to compounds of similar chemical or biologic composition to study agent and/or any of its excipients.
• 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)
• Has active autoimmune disease requiring immunosuppressives or steroids
• 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. COVID19 vaccines are 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 a history of (non-infectious) pneumonitis that required steroids or has current pneumonitis.
• Patient has poorly controlled diabetes mellitus with a glycosylated hemoglobin >8% or poorly controlled steroid-induced diabetes mellitus with a glycosylated hemoglobin of >8%.
• 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.
• Enzyme-inducing antiepileptic drugs (EIAED) need to be discontinued and switched to a non-EIAED 2 weeks prior to starting on trial drugs
• Has a known history of Hepatitis B (defined as Hepatitis B surface antigen [HBsAg] reactive) or known active Hepatitis C virus (defined as HCV RNA [qualitative] is detected) infection.
• Has a known history of active TB (Bacillus Tuberculosis)
• Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent)
• Patients who have undergone prior allogeneic stem cell transplant
• Patients who have large pleural effusions, ascites or full body edema
• Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial
• Is pregnant or breastfeeding or expecting to conceive or father children within the projected duration of the study, starting with the screening visit through 120 days after the last dose of trial treatment

Where it is running

• Brigham and Women's Hospital — Boston, Massachusetts, United States (enrolling)
• Dana Farber Cancer Institute — Boston, Massachusetts, United States (enrolling)

Full record on ClinicalTrials.gov

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