The primary objective of Stage 1 is to evaluate the safety of nivolumab consolidation after completion of HD-MTX containing induction chemotherapy in older subjects with PCNSL in terms of a tolerated dose (based on dose-limiting toxicities) for the expansion phase of the study (Stage 2).The primary objective of Stage 2 is to evaluate the efficacy of nivolumab consolidation after completion of HD-MTX containing induction chemotherapy in terms of the 2-year progression-free survival rate and compare to relevant historical controls
This is a 2-stage phase 1B study of nivolumab consolidation following completion of HD-MTX containing induction chemotherapy in older (≥ 65 years old) patients with previously untreated primary CNS lymphoma. Stage 1 is designed to evaluate the safety of nivolumab consolidation. We plan to use 3+3 design and start at the FDA approved single agent dose of nivolumab 480 mg intravenously every 4 weeks. Stage 2 is designed to evaluate the safety as well as efficacy of nivolumab consolidation after HD-MTX containing induction chemotherapy in an expansion cohort.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
14
HD-MTX containing induction chemotherapy (per standard of care) followed by Nivolumab consolidation.
Dana Farber Cancer Institute
Brookline, Massachusetts, United States
UNC Hospitals, The University of North Carolina at Chapel Hill
Chapel Hill, North Carolina, United States
Levine Cancer Institute
Charlotte, North Carolina, United States
The University of Texas - MD Anderson Cancer Center
Houston, Texas, United States
Safety of Nivolumab in Older Subjects
The primary endpoint for the Stage 1 phase of the study is dose-limiting toxicity which will be assessed for each Stage 1 subject using the DLT criteria
Time frame: Until up to 6 subjects can be adequately assessed for DLT.
Efficacy of Nivolumab
The primary endpoint for the Stage 1 phase of the study is the 2-year progression-free endpoint which will be determined for each subject as a binary variable indicating if they are alive and progression-free at 2 years (PFS2)
Time frame: 2 years
Progression Free Survival (PFS)
PFS is defined as the duration of time from enrollment to first occurrence of either progressive disease or death.
Time frame: 2 years
Overall Survival (OS)
OS is defined as the duration from enrollment to the date of death from any cause.
Time frame: 2 years
Objective and Complete Response Rates
Objective response will be determined for each subject as a binary variable indicating if they have achieved a best overall response of CR or PR as determined by the International Criteria for PCNSL (IPCG). Complete response will be determined for each subject as a binary variable indicating if they have achieved a best overall response of CR as determined by the International Criteria for PCNSL(IPCG).
Time frame: approx. 2 years
Conversion Rate from Partial to Complete Response
Response conversion will be determined for each subject who achieve a best overall response of PR during induction therapy as a binary variable indicating if the subsequently achieve a best overall response of CR to nivolumab consolidation therapy.
Time frame: approx. 2 years
Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]
Adverse events will be collected for each subject using NCI CTCAE v5.0 criteria. A binary variable will be determined for each subject indicating whether or not the subject experienced an AESI during treatment with nivolumab consolidation therapy, across any cycle nivolumab treatment administration.
Time frame: up to 30 days after last dose of Nivolumab
Subset Analysis of 2 Year Progression Free Survival
A subset analysis of the primary population will be performed on those members of the evaluable population for the primary objective completing at least two cycles of nivolumab. PFS is defined as the duration of time from enrollment to first occurrence of either progressive disease or death.
Time frame: 2 years
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