NCT03788291

Acalabrutinib and High Frequency Low Dose Subcutaneous Rituximab in Patients With Previously Untreated Chronic Lymphocytic Leukemia / Small Lymphocytic Lymphoma

Phase II Study of Acalabrutinib and High Frequency Low Dose Subcutaneous Rituximab in Patients With Previously Untreated CLL/SLL

• Status: Completed
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 39 (actual)
• Sponsor: University of Rochester · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

The main purpose of this research study is to find out if the combination of acalabrutinib and high frequency low dose subcutaneous rituximab is safe and effective in patients who have previously untreated chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL).

Detailed description

Despite an array of available therapies, CLL remains an incurable disease. Furthermore, the presence of certain cytogenetic abnormalities and high-risk mutational features predicts for a reduced response to treatment, and as a result, a shorter period of progression-free survival. The development of a well-tolerated more effective, easily administered and limited duration therapy would be a major contribution to the management of CLL and other B cell malignancies. Acalabrutinib is an imidazopyrazine analogue and a potent inhibitor of BTK in vitro and in vivo. Acalabrutinib shows improved selectivity for BTK compared with ibrutinib. Functional inhibition of non-target cells (eg, T cells, NK cells, platelets) was not observed for acalabrutinib at clinically relevant concentrations. Rituximab is a chimeric monoclonal antibody targeting CD20 FDA approved for the treatment of CLL/SLL using intravenous or subcutaneous formulations. Antibody dependent cellular phagocytosis may be optimized using high frequency subcutaneous administration of anti-CD20 monoclonal antibodies. Unlike ibrutinib, acalabrutinib does not cause significant in vitro inhibition of rituximab induced antibody dependent cellular phagocytosis in vitro. The investigator thus proposes that acalabrutinib would be an ideal partner drug with high frequency low dose SQ rituximab in the treatment of CLL and that the combination will increase the efficacy of therapy for CLL patients by decreasing the time to achievement of complete response and allowing for shorter and less toxic therapy.

Conditions

• Chronic Lymphocytic Leukemia (CLL)
• Small Lymphocytic Lymphoma (SLL)

Interventions

Type	Name	Description
DRUG	Acalabrutinib	100 mg by mouth twice a day starting on day 8 of cycle 1
DRUG	Rituximab	Administered 2 times weekly for 6 cycles. Initial dose day 1: 50 mg IV, then 50 mg SQ thereafter.

Timeline

• Start date: 2019-03-25
• Primary completion: 2023-05-19
• Completion: 2023-05-19
• First posted: 2018-12-27
• Last updated: 2024-09-26
• Results posted: 2024-09-26

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study