This phase II trials studies how well acalabrutinib with or without obinutuzumab works in treating patients with early-stage chronic lymphocytic leukemia or small lymphocytic lymphoma. Acalabrutinib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Immunotherapy with monoclonal antibodies, such as obinutuzumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. It is not yet known whether giving acalabrutinib with or without obinutuzumab will work better in treating patients with early-stage chronic lymphocytic leukemia or small lymphocytic lymphoma.
Age >= 18 years
Biopsy-proven small lymphocytic lymphoma (SLL) , or
The population of lymphocytes share both B-cell antigens (CD19, CD20 [typically dim expression], or CD23) as well as CD5 in the absence of other pan-T-cell markers (CD3, CD2, etc.)
Clonality as evidenced by kappa or lambda light chain expression (typically dim immunoglobulin expression) or other genetic method (e.g. IGHV analysis)
Date of CLL/SLL diagnosis >= 24 months prior to registration
Prior exposure to ibrutinib or to a BCR inhibitor (e.g. Btk or PI3 kinase or Syk inhibitors) or a BCL-2 inhibitor (e.g. venetoclax)
Known central nervous system (CNS) lymphoma or leukemia
Evidence of progressive marrow failure as manifested by the development of or worsening anemia (=< 11 g/dL) and/or thrombocytopenia (=< 100 x 10^9/L) not due to autoimmune disease
Parallel
Acalabrutinib
DrugGiven PO
Laboratory Biomarker Analysis
Other interventionCorrelative studies
Obinutuzumab
Biological/VaccineGiven IV
Patient Observation
Other interventionUndergo observation
Quality-of-Life Assessment
Other interventionAncillary studies
Rate of minimal residual disease (MRD)-negative complete response (Arm A and Arm B)
Defined as an objective status of complete response (CR) or CR with incomplete marrow recovery (CRi) along with MRD negativity in the bone marrow by flow cytometry. Will be compared between the two arms. The proportion of successes will be estimated in each arm by the number of successes divided by the total number of evaluable patients. Ninety-five percent confidence intervals for the true success proportion will be calculated in each arm based on the normal approximation. Comparison of MRD-negative complete response rates between the two treatment groups will be performed using a one-sided z-test (based on normal approximation with pooled variance of standardized test statistics) at significance level 0.10.
Time to first therapy (TFT) in patients (Arm C)
Defined as the time from the date of registration to the date of initiation of treatment for CLL.
Overall response rate (Arms A and B)
Will be assessed in each arm by the number of patients who achieve complete remission (CR), complete remission with incomplete count recovery (CRi), clinical complete response (CCR), nodular partial response (nPR), or partial response (PR) at any time during treatment.
Progression-free survival (Arms A and B)
Defined as the time from randomization to the earliest date of documentation of disease progression or death due to any cause.
Time to next therapy (Arms A and B)
Defined as the time from the date of randomization to the date of initiation of subsequent treatment for CLL.
Overall survival (Arms A and B)
Defined as the time from randomization until death due to any cause.
Quality of life
Will be assessed using the Functional Assessment of Cancer Therapy-General (FACT-G), a 27-item questionnaire that measures Health-related quality of life (HRQoL) in cancer patients. Responses to each question are scored on a 5-point Likert scale ranging from 0 (Not at all) to 4 (Very much). Possible total scores range from 0-108, with higher scores indicating a better outcome/better quality QOL.
T-cells, natural killer (NK)-cells, and NK-T cells
Will be assessed in peripheral blood immune profile using 8-color flow cytometry. Values over time will be summarized graphically and descriptively. Paired sample approaches (Wilcoxon signed rank test) for these types of quantitative measures will be used to assess differences over time. Differences between treatments (Arms A and B only) will be assessed.
Bone marrow hematopoiesis (Arms A and B)
will be evaluated by estimation of colony forming capacity by purified hematopoietic stem cells (HSCs) and their differentiated progeny (i.e. multipotent progenitor, common myeloid progenitor, common lymphoid progenitor) as continuous measures. Degree of cytopenia in the peripheral blood will be evaluated on a continuous scale for each blood cell component (hemoglobin, platelets, etc.). In each arm, correlation between each blood cell component and its corresponding pre-cursor will be evaluated using Spearman's rank correlation coefficients.
Percent killing of chronic lymphocytic leukemia (CLL) B-cells (Arms A and B)
Will be measured as a continuous measure. In each arm, the relationship between percent killing and response (responder versus \[vs.\] non-responder) after 12 cycles of treatment will be evaluating using Wilcoxon's rank sum test.
Click on the lead sponsor to view all of their trials.
