Acalabrutinib and High Frequency Low Dose Subcutaneous Rituximab in Patients With Previously Untreated Chronic Lymphocytic Leukemia / Small Lymphocytic Lymphoma
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|ClinicalTrials.gov Identifier: NCT03788291|
Recruitment Status : Recruiting
First Posted : December 27, 2018
Last Update Posted : January 13, 2020
|Condition or disease||Intervention/treatment||Phase|
|Chronic Lymphocytic Leukemia (CLL) Small Lymphocytic Lymphoma (SLL)||Drug: Acalabrutinib Drug: Rituximab||Phase 2|
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.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||40 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Phase II Study of Acalabrutinib and High Frequency Low Dose Subcutaneous Rituximab in Patients With Previously Untreated CLL/SLL|
|Actual Study Start Date :||March 25, 2019|
|Estimated Primary Completion Date :||February 1, 2023|
|Estimated Study Completion Date :||February 1, 2024|
Experimental: Acalabrutinib and Rituximab treatment
Rituximab: administered 2 times weekly for 6 cycles. Initial dose day 1: 50 mg IV, Then 50 mg SQ thereafter.
Acalabrutinib: 100 mg po BID starting on day 8 of cycle 1.
100 mg by mouth twice a day starting on day 8 of cycle 1
Administered 2 times weekly for 6 cycles. Initial dose day 1: 50 mg IV, then 50 mg SQ thereafter.
- Proportion of subjects with a complete response rate (CR) at 1 year of therapy [ Time Frame: 1 year ]
To satisfy criteria for a CR, all of the following criteria must be met:
- No evidence of new disease
- ALC in peripheral blood of <4 x 109/L
- Regression of all target nodal masses to normal size ≤1.5 cm in the LD
- Normal spleen and liver size
- Regression to normal of all nodal non-target disease and disappearance of all detectable non-nodal, non-target disease
- Morphologically negative bone marrow defined as <30% of nucleated cells being lymphoid cells and no lymphoid nodules in a bone marrow sample (the presence of benign reactive nodules is still compatible with a CR)
- Absence of constitutional symptoms
Peripheral blood counts meeting all of the following criteria:
- ANC >1.5 x 109/L without need for exogenous growth factors (e.g., G-CSF)
- Platelet count ≥100 x 109/L without need for exogenous growth factors
- Hemoglobin ≥110 g/L (11.0 g/dL) without red blood cell transfusions or need for exogenous growth factors (e.g., erythropoietin)
- Proportion of subjects with minimal residual disease in peripheral blood and bone [ Time Frame: 1 year ]6-color flow cytometry
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03788291
|Contact: Robin Boerman||585-273-1507||Robin_Boerman@URMC.Rochester.edu|
|United States, New York|
|University of Rochester||Recruiting|
|Rochester, New York, United States, 14642|
|Contact: Andrew Bui|
|Principal Investigator:||Paul Barr||University of Rochester|