RECRUITING

Modified VR-CAP and Acalabrutinib as First Line Therapy for the Treatment of Transplant-Eligible Patients With Mantle Cell Lymphoma

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

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.

Official Title

A Phase II Study of Modified VR-CAP and Acalabrutinib as First Line Therapy for Transplant-Eligible Patients With Mantle Cell Lymphoma

Quick Facts

Study Start:2021-08-03

Study Completion:2028-08-03

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT04626791

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:18 Years to 75 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion Criteria
* 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 * Provide informed written consent * Willing to return to enrolling institution for follow-up (during the Active Monitoring Phase of the study) * Hematologic labs must be obtained within =\< 14 days of registration * Willing and able to participate in all required evaluations and procedures in this study protocol * Ability to understand the purpose and risks of the study and provide signed and dated informed consent and authorization to use protected health information	* 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 * Note: H2-receptor agonists are not exclusionary * 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 * Active or chronic uncontrolled hepatitis B or hepatitis C infection. Patients with positive hepatitis B core antibody positive require negative polymerase chain reaction (PCR) prior to enrollment. Hepatitis B surface antigen positive or PCR positive patients will be excluded. Patients with hepatitis C must have negative hepatitis C virus (HCV) ribonucleic acid (RNA) for inclusion * 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 * Receiving any other investigational agent which would be considered as a treatment for the primary neoplasm * Other active malignancy =\< 2 years prior to registration. EXCEPTIONS: Non-melanotic skin cancer localized prostate cancer, or carcinoma-in-situ of the breast or cervix. NOTE: If there is a history or prior malignancy, patients must not be receiving other specific treatment for their cancer * Pregnant and/or breastfeeding * Has difficulty with or is unable to swallow oral medication, or has significant gastrointestinal disease that would limit absorption of oral medication * Presence of a gastrointestinal ulcer diagnosed by endoscopy within 3 months before screening. unless directly due to MCL Involvement by endoscopic or histologic evaluation * Major surgical procedure within 28 days of first dose of study drug. NOTE: If a subject had major surgery, they must have recovered adequately from any toxicity and/or complications from the intervention before the first dose of study drug * Concurrent participation in another therapeutic clinical trial

Inclusion Criteria

Exclusion Criteria

* 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
* Provide informed written consent
* Willing to return to enrolling institution for follow-up (during the Active Monitoring Phase of the study)
* Hematologic labs must be obtained within =\< 14 days of registration
* Willing and able to participate in all required evaluations and procedures in this study protocol
* Ability to understand the purpose and risks of the study and provide signed and dated informed consent and authorization to use protected health information

* 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
* Note: H2-receptor agonists are not exclusionary
* 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
* Active or chronic uncontrolled hepatitis B or hepatitis C infection. Patients with positive hepatitis B core antibody positive require negative polymerase chain reaction (PCR) prior to enrollment. Hepatitis B surface antigen positive or PCR positive patients will be excluded. Patients with hepatitis C must have negative hepatitis C virus (HCV) ribonucleic acid (RNA) for inclusion
* 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
* Receiving any other investigational agent which would be considered as a treatment for the primary neoplasm
* Other active malignancy =\< 2 years prior to registration. EXCEPTIONS: Non-melanotic skin cancer localized prostate cancer, or carcinoma-in-situ of the breast or cervix. NOTE: If there is a history or prior malignancy, patients must not be receiving other specific treatment for their cancer
* Pregnant and/or breastfeeding
* Has difficulty with or is unable to swallow oral medication, or has significant gastrointestinal disease that would limit absorption of oral medication
* Presence of a gastrointestinal ulcer diagnosed by endoscopy within 3 months before screening. unless directly due to MCL Involvement by endoscopic or histologic evaluation
* Major surgical procedure within 28 days of first dose of study drug. NOTE: If a subject had major surgery, they must have recovered adequately from any toxicity and/or complications from the intervention before the first dose of study drug
* Concurrent participation in another therapeutic clinical trial

Contacts and Locations

Principal Investigator

Stephen D Smith

PRINCIPAL_INVESTIGATOR

Academic and Community Cancer Research United

Study Locations (Sites)

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

Collaborators and Investigators

Sponsor: Academic and Community Cancer Research United

Stephen D Smith, PRINCIPAL_INVESTIGATOR, Academic and Community Cancer Research United

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2021-08-03

Study Completion Date2028-08-03

Study Record Updates

Study Start Date2021-08-03

Study Completion Date2028-08-03

Terms related to this study

Additional Relevant MeSH Terms

Mantle Cell Lymphoma