A Pilot Study of Acalabrutinib With Bendamustine / Rituximab Followed by Cytarabine / Rituximab for Untreated Mantle Cell Lymphoma
Overview
- Phase
- Phase 2
- Intervention
- Leukapheresis
- Conditions
- Mantle Cell Lymphoma
- Sponsor
- Washington University School of Medicine
- Enrollment
- 13
- Locations
- 2
- Primary Endpoint
- Stem Cell Mobilization Success Rate With Cytarabine and Rituximab
- Status
- Completed
- Last Updated
- 11 days ago
Overview
Brief Summary
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.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Histologically confirmed mantle cell lymphoma with documented expression of Cyclin D1 by immune-histochemical stains and/or t(11;14) by cytogenetics or FISH.
- •Presence of evaluable disease by PET imaging per the Lugano classification.
- •Eligible for autologous stem cell transplantation.
- •Between 18 and 70 years of age, inclusive.
- •ECOG performance status ≤ 2
- •Normal bone marrow and organ function as defined below:
- •Absolute neutrophil count ≥ 1,000/mcL unless, in the opinion of the treating physician, neutropenia is due to splenomegaly or bone marrow involvement
- •Platelets ≥ 100,000/mcL unless, in the opinion of the treating physician, thrombocytopenia is due to splenomegaly or bone marrow involvement
- •Total bilirubin ≤ 2.0 x IULN and AST(SGOT)/ALT(SGPT) ≤ 3.0 x IULN except when, in the opinion of the treating physician, elevation is due to direct involvement of lymphoma (e.g. hepatic infiltration or biliary obstruction due to lymphoma) or Gilbert's disease
- •Creatinine ≤ IULN OR creatinine clearance ≥ 40 mL/min for patients with creatinine levels above institutional normal
Exclusion Criteria
- •Any previous chemotherapy or radiation for mantle cell lymphoma. Short course of steroids for symptom relief prior to presentation is permissible.
- •Symptomatic meningeal or parenchymal brain lymphoma.
- •Prior exposure to a BTK inhibitor.
- •Currently receiving any other investigational agents.
- •A history of allergic reactions attributed to compounds of similar chemical or biologic composition to acalabrutinib, rituximab, cytarabine, bendamustine, or other agents used in the study.
- •Received a live virus vaccination within 28 days of first dose of study drug.
- •Uncontrolled active systemic fungal, bacterial, viral, or other infection (defined as exhibiting ongoing signs/symptoms related to the infection and without improvement, despite appropriate antibiotics or other treatment), or intravenous anti-infective treatment within 2 weeks before first dose of study drug.
- •Clinically significant cardiovascular disease such as uncontrolled or symptomatic arrhythmias, congestive heart failure, or myocardial infarction within 6 months of screening, or any Class 3 or 4 cardiac disease as defined by the New York Heart Association Functional Classification, or corrected QT interval (QTc) \> 480 msec at screening. Exception: subjects with controlled, asymptomatic atrial fibrillation during screening are allowed to enroll on study.
- •Malabsorption syndrome, disease significantly affecting gastrointestinal function, or resection of the stomach or small bowel that is likely to affect absorption, symptomatic inflammatory bowel disease, partial or complete bowel obstruction, or gastric restrictions and bariatric surgery, such as gastric bypass.
- •Active bleeding or history of bleeding diathesis (eg, hemophilia or von Willebrand disease).
Arms & Interventions
Bendamustine/Rituximab/Acalabrutinib/Cytarabine
* Patients will receive (6) 28 day cycles * Cycles 1-3 will consist of bendamustine on Days 1 and 2, rituximab on Day 1, and acalabrutinib twice per day (BID) on Days 1 through 28. * Cycles 4-6 will consist of rituximab on Day 1, cytarabine every 12 hours on Days 1 and 2, acalabrutinib BID on Days 1 through 7 and 22 through 28 (one week on, two weeks off, one week on), and growth factors as per institutional standard * After Cycle 6, patients will undergo leukapheresis
Intervention: Leukapheresis
Bendamustine/Rituximab/Acalabrutinib/Cytarabine
* Patients will receive (6) 28 day cycles * Cycles 1-3 will consist of bendamustine on Days 1 and 2, rituximab on Day 1, and acalabrutinib twice per day (BID) on Days 1 through 28. * Cycles 4-6 will consist of rituximab on Day 1, cytarabine every 12 hours on Days 1 and 2, acalabrutinib BID on Days 1 through 7 and 22 through 28 (one week on, two weeks off, one week on), and growth factors as per institutional standard * After Cycle 6, patients will undergo leukapheresis
Intervention: Peripheral blood
Bendamustine/Rituximab/Acalabrutinib/Cytarabine
* Patients will receive (6) 28 day cycles * Cycles 1-3 will consist of bendamustine on Days 1 and 2, rituximab on Day 1, and acalabrutinib twice per day (BID) on Days 1 through 28. * Cycles 4-6 will consist of rituximab on Day 1, cytarabine every 12 hours on Days 1 and 2, acalabrutinib BID on Days 1 through 7 and 22 through 28 (one week on, two weeks off, one week on), and growth factors as per institutional standard * After Cycle 6, patients will undergo leukapheresis
Intervention: Oral rinse
Bendamustine/Rituximab/Acalabrutinib/Cytarabine
* Patients will receive (6) 28 day cycles * Cycles 1-3 will consist of bendamustine on Days 1 and 2, rituximab on Day 1, and acalabrutinib twice per day (BID) on Days 1 through 28. * Cycles 4-6 will consist of rituximab on Day 1, cytarabine every 12 hours on Days 1 and 2, acalabrutinib BID on Days 1 through 7 and 22 through 28 (one week on, two weeks off, one week on), and growth factors as per institutional standard * After Cycle 6, patients will undergo leukapheresis
Intervention: Bone marrow collection
Bendamustine/Rituximab/Acalabrutinib/Cytarabine
* Patients will receive (6) 28 day cycles * Cycles 1-3 will consist of bendamustine on Days 1 and 2, rituximab on Day 1, and acalabrutinib twice per day (BID) on Days 1 through 28. * Cycles 4-6 will consist of rituximab on Day 1, cytarabine every 12 hours on Days 1 and 2, acalabrutinib BID on Days 1 through 7 and 22 through 28 (one week on, two weeks off, one week on), and growth factors as per institutional standard * After Cycle 6, patients will undergo leukapheresis
Intervention: Bendamustine
Bendamustine/Rituximab/Acalabrutinib/Cytarabine
* Patients will receive (6) 28 day cycles * Cycles 1-3 will consist of bendamustine on Days 1 and 2, rituximab on Day 1, and acalabrutinib twice per day (BID) on Days 1 through 28. * Cycles 4-6 will consist of rituximab on Day 1, cytarabine every 12 hours on Days 1 and 2, acalabrutinib BID on Days 1 through 7 and 22 through 28 (one week on, two weeks off, one week on), and growth factors as per institutional standard * After Cycle 6, patients will undergo leukapheresis
Intervention: Rituximab
Bendamustine/Rituximab/Acalabrutinib/Cytarabine
* Patients will receive (6) 28 day cycles * Cycles 1-3 will consist of bendamustine on Days 1 and 2, rituximab on Day 1, and acalabrutinib twice per day (BID) on Days 1 through 28. * Cycles 4-6 will consist of rituximab on Day 1, cytarabine every 12 hours on Days 1 and 2, acalabrutinib BID on Days 1 through 7 and 22 through 28 (one week on, two weeks off, one week on), and growth factors as per institutional standard * After Cycle 6, patients will undergo leukapheresis
Intervention: Acalabrutinib
Bendamustine/Rituximab/Acalabrutinib/Cytarabine
* Patients will receive (6) 28 day cycles * Cycles 1-3 will consist of bendamustine on Days 1 and 2, rituximab on Day 1, and acalabrutinib twice per day (BID) on Days 1 through 28. * Cycles 4-6 will consist of rituximab on Day 1, cytarabine every 12 hours on Days 1 and 2, acalabrutinib BID on Days 1 through 7 and 22 through 28 (one week on, two weeks off, one week on), and growth factors as per institutional standard * After Cycle 6, patients will undergo leukapheresis
Intervention: Cytarabine
Outcomes
Primary Outcomes
Stem Cell Mobilization Success Rate With Cytarabine and Rituximab
Time Frame: Through 5 courses of apheresis (up to 5 days)
-Stem cell mobilization success is defined as a yield of \>2x10\^6 CD34+ stem cells/kg with a maximum of 5 courses of apheresis
Secondary Outcomes
- Pre-transplant Complete Response Rate(Through completion of treatment (estimated to be 6 months))
- Progression-free Survival (PFS)(Through 5 years)
- Safety and Tolerability of Regimen in Subjects With MCL as Measured by Treatment Related Non-hematologic Toxicity of Grade 3 or Higher(30 days following completion of treatment (estimated to be 7 months))
- Overall Response Rate (ORR = Complete Response (CR) + Partial Response (PR)) of Subjects(Through completion of treatment (estimated to be 6 months))
- Overall Survival (OS)(Through 5 years)
- Median Progression-free Survival (PFS)(Up to approximately 5 years of follow-up)
- Overall Survival (OS)(Up to approximately 5 years of follow-up)
- Median Overall Survival (OS)(Up to approximately 5 years of follow-up)