Acalabrutinib Plus RICE for Relapsed/Refractory DLBCL

Summary

Participation Requirements

Description

This is a phase II study with a safety run-in. There will be two planned cohorts, Cohort A and Cohort B. Cohort A will be open to R/R DLBCL patients who are medically eligible for autologous HSCT (autoHSCT). Cohort B will be open to R/R DLBCL patients who are medically ineligible for autologous tran...

This is a phase II study with a safety run-in. There will be two planned cohorts, Cohort A and Cohort B. Cohort A will be open to R/R DLBCL patients who are medically eligible for autologous HSCT (autoHSCT). Cohort B will be open to R/R DLBCL patients who are medically ineligible for autologous transplant. Historical outcomes from completed, published prospective clinical trials using RICE salvage chemotherapy will serve as a comparator population. Safety run-in: To assess for safety of the combination of acalabrutinib and RICE chemotherapy, we will pause enrollment in both cohorts to assess for any safety concerns once a total 10 patients have been enrolled to either cohort. After the first ten patients have all completed at least one cycle of therapy without unacceptable or unexpected concerns, enrollment will resume. If there are concerns about adverse events or the ability of patients to proceed as expected to HSCT, then the study team will convene to determine whether the protocol should be modified. Data obtained for the first ten patients will be included in the data sample for final analysis. Cohort A: After confirmation of medical eligibility for autologous HSCT, patients enrolled in Cohort A will receive 2 cycles of standard dose RICE salvage chemotherapy in combination with acalabrutinib 100mg twice daily (BID) day 1-21 of a 21 day cycle. After 2 cycles of therapy, patients will undergo autologous cell collection per standard institutional procedures. Acalabrutinib will be held 3 days before planned placement of an apheresis collection catheter and resumed 3 days after completion of stem cell collection and catheter removal. Patients will then receive a 3rd cycle of RICE chemotherapy in combination with acalabrutinib 100mg BID. For patients with bone marrow disease at enrollment, a repeat bone marrow will be performed after 2 cycles of salvage therapy, prior to autologous stem cell collection. For patients with continued bone marrow disease after 2 cycles of salvage therapy, a 3rd cycle may be given prior to autologous cell collection. PET-CT (PET3) will be performed 14-21 days after day 1 of cycle 3 to assess response. Those patients with complete response (CR) or partial response (PR) after PET3 will move onto autologous transplant with Carmustine, Etoposide, Cytarabine, and Melphalan (BEAM) conditioning within 28-42 days of PET3. After adequate hematopoietic recovery (expected around 30 days after autologous HSCT), patients will restart acalabrutinib 100mg BID as maintenance therapy for a period of 12 months. Patients with a minor response (MR) or stable disease (SD) after PET3 will delay HSCT and will continue acalabrutinib 100mg BID with repeat PET every 6 weeks. If patient converts to CR at subsequent PET-CT, they may proceed with BEAM autologous HSCT within 28-42 days of achieving this response followed by 12 months of post-transplant acalabrutinib maintenance. Patients with continued PR/MR/SD may continue on study, if felt to be clinically benefitting without limiting toxicity, but will not receive a transplant. Patients demonstrating progressive disease (PD) at any stage will be withdrawn from study treatment but their outcomes will be tracked and included in final data analysis. Cohort B: Patients medically ineligible for autologous HSCT but fit for salvage chemotherapy will receive 3 cycles or RICE salvage chemotherapy in combination with acalabrutinib 100mg BID day 1-21 of a 21 day cycle followed by PET-CT (PET3) 14-21 days after start of Cycle 3. Patients with CR/PR/MR/SD would continue with acalabrutinib maintenance with repeat PET-CT every 3 months until disease progression or toxicity. Patients demonstrating progressive disease (PD) will be withdrawn from study treatment but their outcomes will be tracked and included in final data analysis. Establishing the feasibility of combining acalabrutinib with RICE chemotherapy in transplant eligible and transplant ineligible patients with R/R DLBCL will provide the foundation for a larger study of efficacy and long-term outcomes of the combination therapy for patients with R/R DLBCL. Such a study, if demonstrative of improvements in the complete response rate to salvage therapy at PET3, could provide evidence to support a new standard of care of for patients with R/R DLBCL.

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