This phase II trial investigates how well modified VR-CAP (bortezomib, rituximab, cyclophosphamide, doxorubicin hydrochloride, prednisone, and cytarabine hydrochloride) and acalabrutinib as first line therapy work in treating transplant-eligible patients with mantle cell lymphoma. Modified VR-CAP is a combination of drugs used as standard first line treatment for mantle cell lymphoma. Chemotherapy drugs, such as bortezomib, cyclophosphamide, doxorubicin hydrochloride, and cytarabine hydrochloride, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Rituximab is a monoclonal antibody that binds and depletes malignant B cells, by inducing immune responses and direct toxicity. Acalabrutinib blocks a key enzyme which is needed for malignant cell growth in mantle cell lymphoma. Combining modified VR-CAP and acalabrutinib as first line therapy may be more useful against mantle cell lymphoma compared to the usual treatment.
PRIMARY OBJECTIVE: I. To determine the proportion of complete metabolic responses according to Lugano criteria at the end of study therapy. SECONDARY OBJECTIVES: I. To evaluate the safety of this regimen. II. To determine the proportion of subjects proceeding to autologous stem cell transplant (ASCT). III. To determine the feasibility and results of stem cell mobilization and successful collection. IV. To determine the progression-free survival (PFS) and overall survival (OS) (event monitoring phase), assessed up to 2 years after registration. CORRELATIVE RESEARCH OBJECTIVE: I. To assess minimal residual disease level after 3 and 6 cycles of therapy using the ClonoSEQ (Adaptive Biotechnologies, Seattle, Washington \[WA\]), and to explore the relationship between radiographic complete response (CR) rate and baseline features. OUTLINE: CYCLES 1, 3, AND 5: Patients receive acalabrutinib orally (PO) twice daily (BID) on days 1-21. Patients also receive bortezomib subcutaneously (SC) on days 1, 8, and 15, rituximab (or rituximab and hyaluronidase human) intravenously (IV), cyclophosphamide IV, and doxorubicin hydrochloride IV on day 1, and prednisone PO on days 1-5. CYCLES 2, 4, AND 6: Patients receive acalabrutinib PO BID on days 1-21. Patients also receive rituximab (or rituximab and hyaluronidase human) IV on day 1 and cytarabine IV on days 1-2. Treatment repeats every 21 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up every 6 months for up to 2 years after registration.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
41
Given PO
Given SC
Given IV
Given IV
Given IV
Given PO
Given IV
Given IV
Mount Sinai Hospital
New York, New York, United States
Carolinas Medical Center/Levine Cancer Institute
Charlotte, North Carolina, United States
University of Washington Medical Center - Montlake
Seattle, Washington, United States
Percentage of Complete Responses to Therapy (Complete Metabolic Response [CMR])
Measured according to Lugano criteria. A success is defined as a CMR as the objective status at the end of treatment. The percentage of successes will be estimated by the number of successes divided by the total number of evaluable patients. 95% confidence intervals for the true success proportion will be calculated according to the approach of Duffy and Santner.
Time frame: 29 months
Number of Patients Experiencing at Least One Grade 3 or Greater Adverse Event
The number of patients experiencing at least one grade 3 or greater adverse event will be reported.
Time frame: 29 months
Progression-free Survival
The proportion of patients alive and progression free with 95% CI will be estimated using the method of Kaplan-Meier.
Time frame: 15 months
Overall Survival
The proportion of participants alive and 95% CI will be estimated using the method of Kaplan-Meier.
Time frame: 18 months
Feasibility of Stem Cell Collection
The percentage of patients successfully collecting at least 2 x 10\^6 CD34 cells/kg pt body weight will be calculated and reported.
Time frame: 29 months
Successful Proceeding to Autologous Stem Cell Transplant (ASCT)
The feasibility of stem cell collection will be determined by the proportion of patients successfully collecting at least 2 x 10\^6 CD34 cells/kg pt body weight divided by the total number of evaluable patients proceeding to ASCT.
Time frame: 29 months
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