Modified VR-CAP and Acalabrutinib as First Line Therapy for the Treatment of Transplant-Eligible Patients With Mantle Cell Lymphoma
A Phase II Study of Modified VR-CAP and Acalabrutinib as First Line Therapy for Transplant-Eligible Patients With Mantle Cell Lymphoma
3 other identifiers
interventional
45
1 country
7
Brief Summary
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P25-P50 for phase_2
Started Aug 2021
Longer than P75 for phase_2
7 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
November 3, 2020
CompletedFirst Posted
Study publicly available on registry
November 13, 2020
CompletedStudy Start
First participant enrolled
August 3, 2021
CompletedPrimary Completion
Last participant's last visit for primary outcome
August 3, 2024
CompletedStudy Completion
Last participant's last visit for all outcomes
August 3, 2028
ExpectedMarch 12, 2024
August 1, 2023
3 years
November 3, 2020
March 8, 2024
Conditions
Outcome Measures
Primary Outcomes (1)
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.
At completion of study treatment
Secondary Outcomes (7)
Minimal residual disease (MRD) rate
Up to completion of study treatment
MRD rate
Up to completion of study treatment
Incidence of adverse events
Up to 30 days post-treatment
Progression-free survival
From the date of registration to the date of progression (or relapse),or death due to any cause, whichever comes first, assessed at 2 years post-registration
Overall survival
From registration to death due to any cause, assessed at 2 years post-registration
- +2 more secondary outcomes
Study Arms (1)
Treatment (modified VR-CAP, acalabrutinib)
EXPERIMENTALCYCLES 1, 3, AND 5: Patients receive acalabrutinib PO BID on days 1-21. Patients also receive bortezomib SC on days 1, 8, and 15, rituximab (or rituximab and hyaluronidase human) 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.
Interventions
Given PO
Given SC
Given IV
Given IV
Given IV
Given PO
Given IV
Given IV
Eligibility Criteria
You may qualify if:
- 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
- Documented, fludeoxyglucose F-18 (FDG)-avid measurable disease (at least 1 lesion \>= 1.5 cm in diameter) as detected by positron emission tomography (PET)/computed tomography (CT) and as defined and includes measurable nodal and extranodal disease sites, or splenomegaly measuring more than 13 cm in vertical length
- Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0, 1, 2
- Absolute neutrophil count (ANC) \>= 1000/mm\^3 or \>= 500/mm\^3 if due to lymphomatous marrow or spleen involvement (obtained =\< 30 days prior to registration)
- Platelet count \>= 100,000/mm\^3 or \>= 75,000/mm\^3 if due to lymphomatous marrow or spleen involvement (obtained =\< 30 days prior to registration)
- Total bilirubin =\< 1.5 x upper limit of normal (ULN) (unless documented Gilbert's syndrome, for which total bilirubin =\< 3 x upper limit of normal \[ULN\] is permitted) (obtained =\< 30 days prior to registration)
- Aspartate transaminase (AST) =\< 3 x ULN (obtained =\< 30 days prior to registration)
- Prothrombin time (PT)/international normalized ratio (INR) or partial thromboplastin time (PTT) =\< 2 x ULN, unless elevated due to a lupus anticoagulant (obtained =\< 30 days prior to registration)
- Calculated creatinine clearance must be \>= 30 ml/min using the Cockcroft-Gault formula (obtained =\< 30 days prior to registration)
- Negative pregnancy test done within =\< 14 days prior to registration for women of childbearing potential only
- For women of childbearing potential (WOCBP, defined as premenopausal women capable of becoming pregnant): Must agree to use of highly effective method of birth control during study therapy and until 12 months after last dose of study therapy. NOTE: 'Acceptable' methods are not adequate. Highly effective methods are defined by Clinical Trials Facilitation and Coordination Group \[CTFG\] as having a failure rate of \< 1% per year
- Men must agree to use barrier contraception starting with the first dose of study therapy and through 180 days after completion of study therapy
- +5 more criteria
You may not qualify if:
- 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
- Requiring anticoagulation with warfarin or equivalent vitamin k antagonist
- Uncontrolled AIHA (autoimmune hemolytic anemia) or ITP (idiopathic thrombocytopenia purpura)
- Active bleeding or history of bleeding diathesis (e.g. hemophilia or von Willebrand disease)
- History of stroke or intracranial hemorrhage within 6 months prior to enrollment
- Requires treatment with a strong cytochrome P450 3A4 (CYP3A4) inhibitor/inducer
- Requiring treatment with a proton pump inhibitor. Examples include: dexlansoprazole, esomeprazole, lansoprazole, omeprazole, pantoprazole, rabeprazole, or therapeutic class equivalents
- History of allergic reactions attributed to acalabrutinib, cytarabine, bortezomib, boron, or any of the other agents administered as part of the therapeutic regimen in this study
- Active systemic fungal, bacterial, viral, or other infection that is worsening (defined as increasing signs/symptoms of infection during screening) or, requires intravenous antibiotic therapy
- Co-morbid systemic illnesses or other severe concurrent disease (including major surgery within 2 weeks) which, in the judgment of the investigator, would make the patient inappropriate for entry into this study or interfere significantly with the proper assessment of safety and toxicity of the prescribed regimens
- Known to be human immunodeficiency virus (HIV) positive since antiretroviral therapy has a potential for drug interactions with acalabrutinib
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure or low cardiac ejection fraction (New York Heart Association \[NYHA\] class 3-4 or ejection fraction \[EF\] \< 45%), unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
- +7 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (7)
Ochsner NCI Community Oncology Research Program
New Orleans, Louisiana, 70121, United States
Metropolitan-Mount Sinai Medical Center
Minneapolis, Minnesota, 55404, United States
Mount Sinai Hospital
New York, New York, 10029, United States
Carolinas Medical Center/Levine Cancer Institute
Charlotte, North Carolina, 28203, United States
Fred Hutchinson Cancer Research Center
Seattle, Washington, 98109, United States
University of Washington Medical Center - Montlake
Seattle, Washington, 98195, United States
Aurora Cancer Care-Milwaukee West
Wauwatosa, Wisconsin, 53226, United States
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Stephen D Smith
Academic and Community Cancer Research United
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- NA
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
November 3, 2020
First Posted
November 13, 2020
Study Start
August 3, 2021
Primary Completion
August 3, 2024
Study Completion (Estimated)
August 3, 2028
Last Updated
March 12, 2024
Record last verified: 2023-08