The purpose of this study is to find out if microtransplantation (MST) in combination with nivolumab is safe and effective in patients with relapsed or refractory B cell lymphomas.
This is a non-randomized, open-label, phase 1 study to assess the safety of nivolumab (OPDIVO™, also referred to as BMS-936558, MDX1106, and ONO-4538) in combination with microtransplantation (MST) in patients ≥ 18 years of age with relapsed or refractory B cell lymphomas. A conventional cohorts-of-3 dose-escalation phase I design will be used to determine the optimal dosing strategy of nivolumab in combination with MST. The safety of microtransplantation without nivolumab will be evaluated at the first dose level. If significant, unexpected toxicity is observed at Dose Levels 2 or 3, subsequent cohorts will switch to the alternate dosing schedule to evaluate the safety of dose-reduced nivolumab. After determination of the maximum tolerated dose level, patients will be recruited into an expansion cohort at that level.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Nivolumab (1 mg/Kg or 3 mg/kg) every 2 weeks per cohort dose level and schedule
HLA-mismatched peripheral blood stem cells
Duke University
Durham, North Carolina, United States
Maximum Tolerated Dose of nivolumab in combination with Microtransplantation
In the dose escalation portion, patients will be sequentially enrolled in 3 cohorts at dose levels in a standard 3+3 design until the maximum tolerated dose (MTD) of nivolumab in combination with microtransplantation is reached. The MTD will be defined as the dose level where at most 1 out of 6 patients experience a dose limiting toxicity (DLT) and will also be the recommended phase 2 dose (RP2D) strategy.
Time frame: 1.5 years
Incidence of dose limiting toxicity (DLT)
Dose limiting toxicity will be estimated based on the incidence and intensity of drug related adverse events (AEs) due to microtransplantation and/or nivolumab infusion. DLT will be graded according to the NCI CTCAE version 5.0 criteria and GVHD will be graded by consensus criteria (Przepiorka D et al, BMT, 1995).
Time frame: 4 years
Number of subjects experiencing AE
Time frame: 4 years
Overall response rate (%) is defined as the number of patients achieving a complete response or partial response as a proportion of total patients evaluable for response.
Time frame: 2.5 years
Progression-free Survival (PFS)
progression-free survival (PFS) is defined as the time interval from the time of enrollment on this study to the date of progressive disease (PD) or death, whichever is first reported. Patients are evaluable for PFS if they receive any treatment as part of this study. One- and two-year PFS estimates will also be calculated
Time frame: 4 years
Overall Survival
Overall Survival (OS) is defined as the time interval from the time of enrollment in this study to the date of death from any cause. If the subject is alive or the vital status is unknown, OS will be censored at the date that the subject is last known to be alive, or their last contact date. One- and two-year survival estimates will be generated.
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Time frame: 4 years