New treatment approach for 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

This study is testing a new combination of chemotherapy and targeted therapy to see if it can help patients with mantle cell lymphoma who are eligible for a transplant feel better and have better outcomes.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 45 (estimated)
• Ages: 18 Years to 75 Years
• Sex: All
• Sponsor: Academic and Community Cancer Research United (Academic / other)
• Drugs / interventions: acalabrutinib, radiation, rituximab, Chemotherapy, cyclophosphamide, doxorubicin, prednisone
• Locations: 7 sites (New Orleans, Louisiana and 6 other locations)
• Trial ID: NCT04626791 on ClinicalTrials.gov

What this trial studies

This phase II trial evaluates the effectiveness of a modified VR-CAP regimen combined with acalabrutinib as a first-line therapy for patients with mantle cell lymphoma who are eligible for transplantation. The treatment involves administering a combination of chemotherapy drugs and a targeted therapy to halt cancer cell growth and improve patient outcomes. The study aims to assess the proportion of patients achieving complete metabolic responses, the safety of the treatment, and the feasibility of proceeding to autologous stem cell transplant. Additionally, it will monitor progression-free survival and overall survival over a two-year period.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18-75 with newly diagnosed mantle cell lymphoma requiring systemic therapy and eligible for autologous stem cell transplant.

Not a fit: Patients with prior therapy for mantle cell lymphoma or those with significant comorbidities may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could significantly improve outcomes for patients with mantle cell lymphoma by enhancing response rates and facilitating successful stem cell transplants.

How similar studies have performed: Other studies have shown promise with similar combination therapies in treating mantle cell lymphoma, indicating potential for success in this approach.

Eligibility criteria

Inclusion 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

Exclusion Criteria:

* 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

Where this trial is running

New Orleans, Louisiana and 6 other locations

• Ochsner NCI Community Oncology Research Program — New Orleans, Louisiana, United States (Withdrawn)
• Metropolitan-Mount Sinai Medical Center — Minneapolis, Minnesota, United States (Withdrawn)
• Mount Sinai Hospital — New York, New York, United States (Active_not_recruiting)
• Carolinas Medical Center/Levine Cancer Institute — Charlotte, North Carolina, United States (Recruiting)
• Fred Hutchinson Cancer Research Center — Seattle, Washington, United States (Withdrawn)
• University of Washington Medical Center - Montlake — Seattle, Washington, United States (Recruiting)
• Aurora Cancer Care-Milwaukee West — Wauwatosa, Wisconsin, United States (Withdrawn)

Study contacts

• Principal investigator: Stephen D Smith — Academic and Community Cancer Research United

Conditions Mantle Cell Lymphoma