This study is designed to evaluate the efficacy and safety of acalabrutinib plus bendamustine and rituximab followed by acalabrutinib plus cytarabine and rituximab in subjects with treatment naïve mantle cell lymphoma (MCL), as a preparation for a larger cooperative group trial with the goal of achieving a standard induction regimen for MCL in transplant eligible patients. The investigators hypothesize that the addition of acalabrutinib to BR/CR regimen will prove safe and increase the complete response (CR) rate as well as minimal residual disease (MRD) negativity pre-transplant, thus improving clinical outcomes.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
13
Bendamustine will be administered at a dose of 90 mg/m\^2 IV over 30 minutes on Days 1 and 2 of Cycles 1-3
In Cycle 1, rituximab will be administered at a dose of 375 mg/m\^2 IV on Day 1 or 2 at the investigator's discretion in order to reduce the risk of a first infusion reaction. Rituximab will be given on Day 1 of Cycles 1 through 6.
The capsules should be swallowed intact with water and with or without food.
On Days 1 and 2 of Cycles 4-6, following rituximab dosing, cytarabine will be administered IV every 12 hours for a total of 4 doses.
Until collection of ≥ 2 x 106 CD34+ stem cells / kg
-Baseline, end of Cycle 3, 4-6 weeks after Cycle 6 Day 1, and if the patient discontinues protocol therapy prior to completion of Cycle 6
-Baseline
-Bone marrow will be collected at baseline if the patient requires a marrow for staging purposes and at end of treatment if the patient requires a marrow for restaging.
Washington University School of Medicine
St Louis, Missouri, United States
Stem Cell Mobilization Success Rate With Cytarabine and Rituximab
-Stem cell mobilization success is defined as a yield of \>2x10\^6 CD34+ stem cells/kg with a maximum of 5 courses of apheresis
Time frame: Through 5 courses of apheresis (up to 5 days)
Safety and Tolerability of Regimen in Subjects With MCL as Measured by Treatment Related Non-hematologic Toxicity of Grade 3 or Higher
-Toxicity is measured using NCI Common Terminology Criteria for Adverse Events (CTCAE) version 5.0
Time frame: 30 days following completion of treatment (estimated to be 7 months)
Overall Response Rate (ORR = Complete Response (CR) + Partial Response (PR)) of Subjects
-For definitions of CR and PR please refer to the Recommendations for Initial Evaluation, Staging and Response Assessment of Hodgkin and Non-Hodgkin Lymphoma: The Lugano Classification
Time frame: Through completion of treatment (estimated to be 6 months)
Pre-transplant Complete Response Rate
-For definitions of CR, please refer to the Recommendations for Initial Evaluation, Staging and Response Assessment of Hodgkin and Non-Hodgkin Lymphoma: The Lugano Classification
Time frame: Through completion of treatment (estimated to be 6 months)
Median Progression-free Survival (PFS)
* Kaplan-Meier estimate of the median time of PFS from start of treatment to time of progression or death, whichever occurs first. * Progressive disease: * London Deauville score of 4 or 5 in individual target nodes/masses with an increase in intensity of uptake from the baseline and/or new FDG avid foci consistent with lymphoma at interim or end of treatment assessment. * New FDG avid foci of extranodal disease consistent with lymphoma. If there is concern regarding the etiology of the new lesions, biopsy or interval scan may be considered * New or recurrent FDG avid foci in the bone marrow
Time frame: Up to approximately 5 years of follow-up
Overall Survival (OS)
Time frame: Up to approximately 5 years of follow-up
Median Overall Survival (OS)
* Overall survival (OS) is defined as the time from study registration to date of death due to any cause. * Kaplan-Meier method will be used for analysis.
Time frame: Up to approximately 5 years of follow-up
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