An Early Phase Study of Venetoclax, Lenalidomide, and Rituximab/Hyaluronidase in Slow-Growing Lymphomas That Have Come Back After Treatment or Have Not Responded to Treatment

Summary

Participation Requirements

Description

PRIMARY OBJECTIVE: I. To determine the safety (and the recommended phase 2 dose [RP2D]), of the combination of venetoclax, lenalidomide, and rituximab hyaluronidase in patients with relapsed/refractory (R/R) follicular lymphoma (FL) and marginal zone lymphoma (MZL). SECONDARY OBJECTIVES: I. To deter...

PRIMARY OBJECTIVE: I. To determine the safety (and the recommended phase 2 dose [RP2D]), of the combination of venetoclax, lenalidomide, and rituximab hyaluronidase in patients with relapsed/refractory (R/R) follicular lymphoma (FL) and marginal zone lymphoma (MZL). SECONDARY OBJECTIVES: I. To determine the overall response rate (ORR) with rituximab hyaluronidase, venetoclax, and lenalidomide. II. To determine the 2-year progression-free survival (PFS) with rituximab hyaluronidase, venetoclax, and lenalidomide. III. To determine the overall survival (OS) following therapy with rituximab hyaluronidase, venetoclax, and lenalidomide. CORRELATIVE STUDY OBJECTIVES: I. Describe changes in the level of expression and expression ratio between anti-apoptotic and pro-apoptotic BCL-2 family members before and after therapy with venetoclax/lenalidomide/rituximab hyaluronidase for each patient. II. Examine the metabolic landscape before and after venetoclax/lenalidomide/rituximab hyaluronidase and their effects on mitochondrial metabolism. III. Describe the immune effects of venetoclax and its effects on serum cytokines and different immune cell subsets (e.g. B-cells, T-cells, dendritic cells, etc.) in addition to T-cell activation markers and expression of immune checkpoint proteins. OUTLINE: This is a dose-escalation study of venetoclax. Patient receive venetoclax orally (PO) once daily (QD) on days 1-28. Beginning cycle 2, patients receive lenalidomide PO QD on days 1-21. Patients also receive rituximab intravenously (IV) on days 1, 8, 15, and 22 of cycle 2 and rituximab hyaluronidase (if no significant infusion reaction to rituximab) subcutaneously (SC) on day 1 of cycles 4, 6, 8, 10, and 12. Patients may receive rituximab IV (instead of rituximab hyaluronidase) on days 1, 8, 15, and 22 of cycles 4, 6, 8, 10, and 12 if the patient requires rituximab IV in the opinion of the treating physician. Treatment repeats every 28 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up at 30 days, and then for up to 5 years.

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