This study will be conducted as a Phase Ib, open-label, non-randomized, single-institution study to evaluate the safety and tolerability of carfilzomib in combination with bendamustine and rituximab in patients with relapsed or refractory NHL and to determine the recommended phase II dose and preliminary efficacy of this combination. The study will have two phases: a dose-escalation phase to determine the maximal tolerated dose of carfilzomib in this combination where participants will be monitored for toxicity, tolerability and response and a dose-expansion phase that will determine the preliminary efficacy in patients with Mantle cell lymphoma or any other disease subtype in which there is a preliminary efficacy signal observed. Determination of the maximum tolerated dose (MTD) will follow standard 3+3 design with escalation of the carfilzomib dose only. Dose levels of carfilzomib will be 20 mg/m2, 36 mg/m2, 56 mg/m2, and 70 mg/m2 IV administered weekly on days 2, 9 and 16. The last 3 cohorts will have a starting carfilzomib dose of 20 mg/m2 on days 1, 2. Bendamustine will be administered at the well-tolerated dose of 90 mg/m2 IV on days 1 and 2. Rituximab will be given at a dose of 375 mg/m2 on day 9 of Cycle 1 and day 1 of subsequent cycles. Rituximab will be intentionally delayed to day 9 of cycle 1 to help facilitate performance of the correlative studies.
A Phase Ib Dose Escalation Trial of Carfilzomib in Combination With Bendamustine and Rituximab In Patients With Relapsed or Refractory Non-Hodgkin Lymphoma
Lymphoma, Non-Hodgkin Lymphoma Relapsed Refractory Rituximab Bendamustine Hydrochloride
Open to people ages 18 years and up
Adequate bone marrow function:
Absolute neutrophil count ≥ 1.0 × 109/L Hemoglobin ≥ 8 g/dL (80 g/L) within 14 days prior Cycle 1, Day 1 (subjects may be receiving red blood cell [RBC] transfusions in accordance with institutional guidelines) Platelet count ≥ 75 × 109/L or≥ 50× 109/L if there is lymphoma involvement in the bone marrow, independent of platelet transfusion
Adequate hepatic function:
Serum AST/ALT ≤ 3 times the upper limit of normal Serum direct bilirubin ≤ 2 mg/dL (unless history of Gilbert's)
Adequate renal function:
Creatinine clearance (CrCl) ≥ 30 mL/minute, either measured or calculated using a standard formula (eg, Cockcroft and Gault) Uric acid If elevated, corrected to within laboratory range prior to dosing
Patient has received other investigational drugs within 21 days prior to Cycle 1, Day
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