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

NCT04626791 | Active Not Recruiting Phase 2 Results DMC FDA Drug

• 3 other identifiers: ACCRU-LY-1804NCI-2020-04428P30CA015083
• Study Type: interventional
• Target: 41
• Locations: 1 country
• Sites: 3

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.

Conditions

Mantle Cell Lymphoma

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. 95% confidence intervals for the true success proportion will be calculated according to the approach of Duffy and Santner.

  29 months

Secondary Outcomes (5)

• Number of Patients Experiencing at Least One Grade 3 or Greater Adverse Event

  29 months

• Progression-free Survival

  15 months

• Overall Survival

  18 months

• Feasibility of Stem Cell Collection

  29 months

• Successful Proceeding to Autologous Stem Cell Transplant (ASCT)

  29 months

Other Outcomes (2)

• MRD Rate

  Up to completion of study treatment

• Minimal Residual Disease (MRD) Rate

  Up to completion of study treatment

Study Arms (1)

Treatment (modified VR-CAP, acalabrutinib)

EXPERIMENTAL

CYCLES 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.

Drug: Acalabrutinib; Drug: Bortezomib; Drug: Cyclophosphamide; Drug: Cytarabine; Drug: Doxorubicin Hydrochloride; Drug: Prednisone; Biological: Rituximab; Biological: Rituximab and Hyaluronidase Human

Interventions

Acalabrutinib DRUG

Given PO

Also known as: ACP-196, Bruton Tyrosine Kinase Inhibitor ACP-196

Treatment (modified VR-CAP, acalabrutinib)

Bortezomib DRUG

Given SC

Also known as: [(1R)-3-Methyl-1-[[(2S)-1-oxo-3-phenyl-2-[(pyrazinylcarbonyl)amino]propyl]amino]butyl]boronic Acid, LDP 341, MLN341, PS-341, PS341, Velcade

Treatment (modified VR-CAP, acalabrutinib)

Cyclophosphamide DRUG

Given IV

Also known as: (-)-Cyclophosphamide, 2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate, Carloxan, Ciclofosfamida, Ciclofosfamide, Cicloxal, Clafen, Claphene, CP monohydrate, CTX, CYCLO-cell, Cycloblastin, Cycloblastine, Cyclophospham, Cyclophosphamid monohydrate, Cyclophosphamide Monohydrate, Cyclophosphamidum, Cyclophosphan, Cyclophosphane, Cyclophosphanum, Cyclostin, Cyclostine, Cytophosphan, Cytophosphane, Cytoxan, Fosfaseron, Genoxal, Genuxal, Ledoxina, Mitoxan, Neosar, Revimmune, Syklofosfamid, WR- 138719

Treatment (modified VR-CAP, acalabrutinib)

Cytarabine DRUG

Given IV

Also known as: .beta.-Cytosine arabinoside, 1-.beta.-D-Arabinofuranosyl-4-amino-2(1H)pyrimidinone, 1-.beta.-D-Arabinofuranosylcytosine, 1-Beta-D-arabinofuranosyl-4-amino-2(1H)pyrimidinone, 1-Beta-D-arabinofuranosylcytosine, 1.beta.-D-Arabinofuranosylcytosine, 2(1H)-Pyrimidinone, 4-Amino-1-beta-D-arabinofuranosyl-, 2(1H)-Pyrimidinone, 4-amino-1.beta.-D-arabinofuranosyl-, Alexan, Ara-C, ARA-cell, Arabine, Arabinofuranosylcytosine, Arabinosylcytosine, Aracytidine, Aracytin, Aracytine, Beta-Cytosine Arabinoside, CHX-3311, Cytarabinum, Cytarbel, Cytosar, Cytosine Arabinoside, Cytosine-.beta.-arabinoside, Cytosine-beta-arabinoside, Erpalfa, Starasid, Tarabine PFS, U 19920, U-19920, Udicil, WR-28453

Treatment (modified VR-CAP, acalabrutinib)

Doxorubicin Hydrochloride DRUG

Given IV

Also known as: 5,12-Naphthacenedione, 10-[(3-amino-2,3,6-trideoxy-alpha-L-lyxo-hexopyranosyl)oxy]-7,8, 9,10-tetrahydro-6,8,11-trihydroxy-8-(hydroxyacetyl)-1-methoxy-, hydrochloride, (8S-cis)- (9CI), ADM, Adriacin, Adriamycin, Adriamycin Hydrochloride, Adriamycin PFS, Adriamycin RDF, ADRIAMYCIN, HYDROCHLORIDE, Adriamycine, Adriblastina, Adriblastine, Adrimedac, Chloridrato de Doxorrubicina, DOX, DOXO-CELL, Doxolem, Doxorubicin HCl, Doxorubicin.HCl, Doxorubin, Farmiblastina, FI 106, FI-106, hydroxydaunorubicin, Rubex

Treatment (modified VR-CAP, acalabrutinib)

Prednisone DRUG

Given PO

Also known as: .delta.1-Cortisone, 1, 2-Dehydrocortisone, Adasone, Cortancyl, Dacortin, DeCortin, Decortisyl, Decorton, Delta 1-Cortisone, Delta-Dome, Deltacortene, Deltacortisone, Deltadehydrocortisone, Deltasone, Deltison, Deltra, Econosone, Lisacort, Meprosona-F, Metacortandracin, Meticorten, Ofisolona, Orasone, Panafcort, Panasol-S, Paracort, Perrigo Prednisone, PRED, Predicor, Predicorten, Prednicen-M, Prednicort, Prednidib, Prednilonga, Predniment, Prednisone Intensol, Prednisonum, Prednitone, Promifen, Rayos, Servisone, SK-Prednisone

Treatment (modified VR-CAP, acalabrutinib)

Rituximab BIOLOGICAL

Given IV

Also known as: ABP 798, BI 695500, C2B8 Monoclonal Antibody, Chimeric Anti-CD20 Antibody, CT-P10, IDEC-102, IDEC-C2B8, IDEC-C2B8 Monoclonal Antibody, MabThera, Monoclonal Antibody IDEC-C2B8, PF-05280586, Riabni, Rituxan, Rituximab ABBS, Rituximab ARRX, Rituximab Biosimilar ABP 798, Rituximab Biosimilar BI 695500, Rituximab Biosimilar CT-P10, Rituximab Biosimilar GB241, Rituximab Biosimilar IBI301, Rituximab Biosimilar JHL1101, Rituximab Biosimilar PF-05280586, Rituximab Biosimilar RTXM83, Rituximab Biosimilar SAIT101, Rituximab Biosimilar SIBP-02, rituximab biosimilar TQB2303, Rituximab PVVR, rituximab-abbs, Rituximab-arrx, Rituximab-pvvr, RTXM83, Ruxience, Truxima

Treatment (modified VR-CAP, acalabrutinib)

Rituximab and Hyaluronidase Human BIOLOGICAL

Given IV

Also known as: Rituxan Hycela, Rituximab Plus Hyaluronidase, Rituximab/Hyaluronidase, Rituximab/Hyaluronidase Human

Treatment (modified VR-CAP, acalabrutinib)

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

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

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

Sponsors & Collaborators

• Academic and Community Cancer Research United: lead
• National Cancer Institute (NCI): collaborator

Study Sites (3)

Mount Sinai Hospital

New York, New York, 10029, United States

Location

Carolinas Medical Center/Levine Cancer Institute

Charlotte, North Carolina, 28203, United States

Location

University of Washington Medical Center - Montlake

Seattle, Washington, 98195, United States

Location

Related Publications (1)

• Smith SD, Sundaram S, Giri S, Ness A, Wang Y, Gopal AK, Pang Y, Tatoian ET, Grossfeld T, Lynch RC, Warren EH, Nowakowski GS, Park SI. Outcomes From the Multicenter ACCRU-LY-1804/CARiBOU TRIAL (Cytarabine, Acalabrutinib and Rituximab Integrated With Bortezomib-Based Outpatient Therapy) in 1st Line Mantle Cell Lymphoma. Am J Hematol. 2026 Jun 17. doi: 10.1002/ajh.70406. Online ahead of print.

  PMID: 42305039 DERIVED

MeSH Terms

Conditions

Lymphoma, Mantle-Cell

Interventions

acalabrutinib; Bortezomib; Cyclophosphamide; Cytarabine; Doxorubicin; Prednisone; deltacortene; prednylidene; Rituximab; CT-P10; Hyaluronoglucosaminidase

Condition Hierarchy (Ancestors)

Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Boronic Acids; Acids, Noncarboxylic; Acids; Inorganic Chemicals; Boron Compounds; Organic Chemicals; Pyrazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Phosphoramides; Organophosphorus Compounds; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Arabinonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates; Pregnadienediols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Glycoside Hydrolases; Hydrolases; Enzymes; Enzymes and Coenzymes; Polysaccharide-Lyases; Carbon-Oxygen Lyases; Lyases

Results Point of Contact

• Title: Stephen D. Smith M. D.
• Organization: University of Washington/Fred Hutchinson Cancer Research Center

Ssmith50@fredhutch.org

507/538-7448

Study Officials

• Stephen D Smith

  Academic and Community Cancer Research United

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

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, 2025
• Study Completion (Estimated): August 3, 2028
• Last Updated: July 22, 2026
• Results First Posted: July 22, 2026

Record last verified: 2026-06

Locations

US (3)