Pembrolizumab + Chemotherapy in Newly Diagnosed PCNSL
NCT Number: NCT06475235
Status: RECRUITING
Study Type: INTERVENTIONAL
Phases: PHASE1
Conditions: Lymphoma|Primary Central Nervous System Lymphoma
Interventions: DRUG: Pembrolizumab|DRUG: Methotrexate|DRUG: Temozolomide|DRUG: Rituximab
Sponsor: Dana-Farber Cancer Institute
Collaborators: Merck Sharp & Dohme LLC
Sex: ALL
Age: ADULT, OLDER_ADULT
Enrollment: 15
Study Design: Allocation: NON_RANDOMIZED|Intervention Model: SEQUENTIAL|Masking: NONE|Primary Purpose: TREATMENT
Start Date: 2024-08
Completion Date: 2027-06-30
Locations: Brigham and Women's Hospital, Boston, Massachusetts, 02115, United States|Dana Farber Cancer Institute, Boston, Massachusetts, 02215, United States

Summary:
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)

Primary Outcome Measures: Number of Patients Experienced Dose Limiting Toxicity (DLT), Dose-limiting toxicities (DLTs) will be defined as any grade ≥3 non-hematologic toxicity (with exceptions), grade 4 neutropenia lasting \>7 days or febrile neutropenia, grade 4 thrombocytopenia, grade 3 thrombocytopenia with clinically significant bleeding, any grade 5 toxicity or dose delays for \>14 consecutive days (related to AEs) with exceptions. Toxicities are to be assess according to the CTCAE v5., Up to 28 days
Secondary Outcome Measures: Complete Response Rate (CRR), CRR is defined as the proportion of participants who achieved complete response (CR). Radiographic response will be assessed using IPCG criteria., Up to 16 weeks|Objective Response Rate (ORR), Objective response rate (ORR), defined as best overall response of either complete or partial response, will be assessed among participants who start protocol therapy and have measurable disease at screening. Radiographic response will be assessed using IPCG criteria., Up to 106 weeks|2-Year Progression Free Survival (PFS2), PFS2 is the percent probability estimate at 2 years based on the Kaplan-Meier method. PFS is defined as the duration of time from study entry to documented disease progression (PD) requiring removal from the study or death. Participants alive without PD were censored at the earliest of the date of the last disease evaluation or start of new anticancer therapy., Up to 2 years|Duration of Response (DOR), DOR is defined as the time from date of first documented confirmed objective response to date of first documented progressive disease (PD)., Up to 106 weeks|Median Progression Free Survival (PFS), PFS is defined as the duration of time from study entry to documented disease progression (PD) requiring removal from the study or death. Participants alive without PD were censored at the earliest of the date of the last disease evaluation or start of new anti-cancer therapy., Up to 106 weeks|Median Overall Survival (OS), Overall survival based on the Kaplan-Meier method is defined as the time from registration to death. Participants alive are censored at the last date of contact (including lost-to-follow-up) or at the date of withdrawal of consent, if relevant., Up to 3 years|Frequency of Missed or Delayed doses, Instances of missed or delayed doses due to treatment related toxicity will be noted to assess tolerability throughout study therapy with pembrolizumab and chemotherapy, including beyond the MTD interval., Up to 106 weeks|Percentage of actual planned dosage administration, Instances of actual planned cycles due to treatment related toxicity will be reported as a percentage to assess tolerability throughout study therapy with pembrolizumab and chemotherapy, including beyond the MTD interval., Up to 106 weeks|Percentage of patients that discontinue study drugs due to treatment-related toxicity., Number of patients that discontinue study drugs due to treatment related toxicity; will be reported as a percentage., Up to 106 weeks