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Mantle Cell LymphomaPhase 2NCT04626791

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

A Phase 2 study testing Acalabrutinib, Bortezomib and Cyclophosphamide in people with Mantle Cell Lymphoma, run by Academic and Community Cancer Research United at 3 sites in United States.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 to 75 years
Conditions the study is for
Mantle Cell Lymphoma
What is being tested?
Acalabrutinib, Bortezomib and Cyclophosphamide
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
41 participants
Where
3 sitesUnited States
Study dates
3 Aug 2021to 3 Aug 2028
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 75 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
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  • 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

Who cannot join

  • 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)
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  • 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

Trial locations and contacts

3 sites in 1 country.

United States3 sites

  • Carolinas Medical Center/Levine Cancer Institute

    Charlotte, North Carolina, 28203

  • Mount Sinai Hospital

    New York, New York, 10029

  • University of Washington Medical Center - Montlake

    Seattle, Washington, 98195

Other trials in United States

About this study

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

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.

Read the detailed description

PRIMARY OBJECTIVE:

  1. To determine the proportion of complete metabolic responses according to Lugano criteria at the end of study therapy.

SECONDARY OBJECTIVES:

  1. To evaluate the safety of this regimen. II. To determine the proportion of subjects proceeding to autologous stem cell transplant (ASCT).

III. To determine the feasibility and results of stem cell mobilization and successful collection.

IV. To determine the progression-free survival (PFS) and overall survival (OS) (event monitoring phase), assessed up to 2 years after registration.

CORRELATIVE RESEARCH OBJECTIVE:

  1. To assess minimal residual disease level after 3 and 6 cycles of therapy using the ClonoSEQ (Adaptive Biotechnologies, Seattle, Washington [WA]), and to explore the relationship between radiographic complete response (CR) rate and baseline features.

OUTLINE:

CYCLES 1, 3, AND 5: Patients receive acalabrutinib orally (PO) twice daily (BID) on days 1-21. Patients also receive bortezomib subcutaneously (SC) on days 1, 8, and 15, rituximab (or rituximab and hyaluronidase human) intravenously (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.

After completion of study treatment, patients are followed up every 6 months for up to 2 years after registration.

Medical subject headings
Lymphoma, Mantle-Cell

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • AcalabrutinibDrug

    Also called ACP-196, Bruton Tyrosine Kinase Inhibitor ACP-196

    Given PO

  • BortezomibDrug

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

    Given SC

  • CyclophosphamideDrug

    Also called (-)-Cyclophosphamide, 2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate, Carloxan, Ciclofosfamida

    Given IV

  • CytarabineDrug

    Also called .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

    Given IV

  • Doxorubicin HydrochlorideDrug

    Also called 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

    Given IV

  • PrednisoneDrug

    Also called .delta.1-Cortisone, 1, 2-Dehydrocortisone, Adasone, Cortancyl

    Given PO

  • RituximabBiological

    Also called ABP 798, BI 695500, C2B8 Monoclonal Antibody, Chimeric Anti-CD20 Antibody

    Given IV

  • Rituximab and Hyaluronidase HumanBiological

    Also called Rituxan Hycela, Rituximab Plus Hyaluronidase, Rituximab/Hyaluronidase, Rituximab/Hyaluronidase Human

    Given IV

Study groups in NCT04626791
Study groupRoleWhat they receive
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.
Receives: Drug: Acalabrutinib; Drug: Bortezomib; Drug: Cyclophosphamide; Drug: Cytarabine; Drug: Doxorubicin Hydrochloride; Drug: Prednisone; Biological: Rituximab; Biological: Rituximab and Hyaluronidase Human

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Percentage 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 percentage 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.

    Measured: 29 months

Secondary outcomes (5)

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

    The number of patients experiencing at least one grade 3 or greater adverse event will be reported.

    Measured: 29 months

  2. Progression-free Survival

    The proportion of patients alive and progression free with 95% CI will be estimated using the method of Kaplan-Meier.

    Measured: 15 months

  3. Overall Survival

    The proportion of participants alive and 95% CI will be estimated using the method of Kaplan-Meier.

    Measured: 18 months

  4. Feasibility of Stem Cell Collection

    The percentage of patients successfully collecting at least 2 x 10^6 CD34 cells/kg pt body weight will be calculated and reported.

    Measured: 29 months

  5. Successful Proceeding to Autologous Stem Cell Transplant (ASCT)

    The feasibility of stem cell collection will be determined by the proportion of patients successfully collecting at least 2 x 10^6 CD34 cells/kg pt body weight divided by the total number of evaluable patients proceeding to ASCT.

    Measured: 29 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted13 Nov 2020
  2. Study start3 Aug 2021
  3. Primary completion3 Aug 2025
  4. Study completion3 Aug 2028 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
41 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04626791
Sponsor's protocol ID
ACCRU-LY-1804
Other IDs
NCI-2020-04428, ACCRU-LY-1804, P30CA015083
Status last verified
Jun 2026
First submitted
3 Nov 2020
Last updated
25 Aug 2026
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

Publications

  • 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 Sep;101(9):2190-2196. doi: 10.1002/ajh.70406. Epub 2026 Jun 17.

    PubMed 42305039

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Acalabrutinib, Bortezomib and Cyclophosphamide in people with Mantle Cell Lymphoma, run by Academic and Community Cancer Research United at 3 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 20 inclusion and 24 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: under way, not looking for participants, as of the sponsor's last update on 25 Aug 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 3 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 22 Jul 2026). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Percentage of Complete Responses to Therapy (Complete Metabolic Response [CMR]) (time frame: 29 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04626791, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 Aug 2026.

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