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.
Age 18-75 years
No prior therapy for mantle cell lymphoma (MCL)
MCL in need of systemic therapy, and potentially eligible for ASCT as assessed by the treating physician
Documented histological confirmation of MCL by local institutional review
Prior systemic treatment for mantle cell lymphoma. Short course of steroids (=< 7 days) for symptom management or localized radiation is permissible, as long as measurable disease outside of the radiation field exists
Peripheral neuropathy or neuropathic pain of grade 2 or worse as assessed by the investigator
Prior exposure to bortezomib or a BTK inhibitor
Prior anthracycline exposure unless cumulative prior exposure is under 150 mg per square meter
Single group
Acalabrutinib
DrugGiven PO
Bortezomib
DrugGiven SC
Cyclophosphamide
DrugGiven IV
Cytarabine
DrugGiven IV
Doxorubicin Hydrochloride
DrugGiven IV
Prednisone
DrugGiven PO
Rituximab
Biological/VaccineGiven IV
Rituximab and Hyaluronidase Human
Biological/VaccineGiven IV
Proportion 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 proportion of successes will be estimated by the number of successes divided by the total number of evaluable patients. 9% confidence intervals for the true success proportion will be calculated according to the approach of Duffy and Santner.
Minimal residual disease (MRD) rate
Measured by flow. MRD results will be reported descriptively, and explored for correlation with clinical factors and patient outcomes.
MRD rate
Measured by sequencing. MRD results will be reported descriptively, and explored for correlation with clinical factors and patient outcomes.
Incidence of adverse events
The maximum grade for each type of adverse event will be recorded for each patient, and frequency tables will be reviewed to determine patterns. Additionally, the relationship of the adverse event(s) to the study treatment will be reported.
Progression-free survival
The distribution of progression-free survival will be estimated using the method of Kaplan-Meier.
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Academic and Community Cancer Research United
Lead sponsor
National Cancer Institute (NCI)
Collaborator
