This phase II trial tests the safety, side effects and how well giving tafasitamab with acalabrutinib and venetoclax works for the treatment of chronic lymphocytic leukemia (CLL)/small cell lymphoma (SLL). A monoclonal antibody is a type of protein that can bind to certain targets in the body, such as molecules that cause the body to make an immune response (antigens). Tafasitamab is a monoclonal antibody that binds to CD19 antigen which is found on the surface of most B cells (a type of white blood cell) and some lymphoma cells. This may help the immune system kill cancer cells. Acalabrutinib is in a class of medications called kinase inhibitors. It blocks a protein called BTK, which is present on B-cell (a type of white blood cells) cancers such as mantle cell lymphoma at abnormal levels. This may help keep cancer cells from growing and spreading. Venetoclax is in a class of medications called B-cell lymphoma-2 (BCL-2) inhibitors. It may stop the growth of cancer cells by blocking Bcl-2, a protein needed for cancer cell survival. Giving tafasitamab with acalabrutinib and venetoclax may be safe and effective for treating patients with CLL/SLL.
Documented informed consent of the participant and/or legally authorized representative.
Assent, when appropriate, will be obtained per institutional guidelines
Agreement to allow the use of archival tissue from diagnostic tumor biopsies
If unavailable, exceptions may be granted with study principal investigator (PI) approval
Chronic use of corticosteroids in excess of 20 mg/day prednisone or its equivalent
Major surgery (under general anesthesia) within 30 days prior to therapy
Uncontrolled coagulopathy or bleeding disorder. Direct oral anticoagulants are allowed
Use of moderate or strong cytochrome P450 3A4 (CYP3A4) inducer within 2 weeks of the first day of study therapy. CYP3A inhibitors are allowed
Single group
Acalabrutinib
DrugGiven PO
Biospecimen Collection
Procedure/SurgeryUndergo blood sample collection
Bone Marrow Biopsy
Procedure/SurgeryUndergo bone marrow biopsy
Computed Tomography
Procedure/SurgeryUndergo CT scan
Positron Emission Tomography
Procedure/SurgeryUndergo PET scan
Tafasitamab
Biological/VaccineGiven IV
Venetoclax
DrugGiven PO
Incidence of unacceptable toxicity
Defined as toxicities deemed related (possibly, probably or definitely) to the study drugs.
Complete response with undetectable minimal residual disease (MRD)
Complete response is defined by International Workshop on Chronic Lymphocytic Leukemia (iwCLL) criteria; undetectable is defined as \< 10\^-4 CLL cells in the peripheral blood by flow cytometry. Will be estimated by the proportion of evaluable patients achieving that endpoint, along with the 95% exact binomial confidence interval.
Overall response
Defined as achieving complete response (CR) or partial response (PR) according to iwCLL 2018 guidelines on this study before any documented disease progression or any subsequent treatment. Will be estimated by the proportion of evaluable patients achieving that endpoint, along with the 95% exact binomial confidence interval.
Progression free survival
Will be estimated using the product-limit method of Kaplan and Meier along with the Greenwood estimator of standard error; 95% confidence interval of the PFS estimate at specific timepoint will be constructed based on log-log transformation. Median PFS will be estimated when available.
Duration of response
Will be estimated using the product-limit method of Kaplan and Meier along with the Greenwood estimator of standard error; 95% confidence interval of the DOR estimate at specific timepoint will be constructed based on log-log transformation. Median DOR will be estimated when available.
Overall survival
Will be estimated using the product-limit method of Kaplan and Meier along with the Greenwood estimator of standard error; 95% confidence interval of the OS estimate at specific timepoint will be constructed based on log-log transformation. Median OS will be estimated when available.
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City of Hope Medical Center
Lead sponsor
National Cancer Institute (NCI)
Collaborator
This trial is not recruiting at the moment. You can still explore other options:
