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Mantle Cell LymphomaPhase 2NCT04765111

Acalabrutinib and Rituximab for the Treatment of Previously Untreated Mantle Cell Lymphoma

A Phase 2 study testing Acalabrutinib and Rituximab in people with Mantle Cell Lymphoma, run by M.D. Anderson Cancer Center at 1 site 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 studies the side effects of acalabrutinib and rituximab and its effect in treating patients with previously untreated mantle cell lymphoma. Acalabrutinib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Read more about this study

Who is it for?
Ages 65 years and older
Conditions the study is for
Mantle Cell Lymphoma
What is being tested?
Acalabrutinib and Rituximab
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
53 participants
Where
1 siteUnited States
Study dates
30 Jun 2021to 30 Aug 2028
Phase
Phase 2
Are there results?
Not yet: the study is under way

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 65 years and older
  • All sexes
  • No healthy volunteers
  • Older adult

Who may be able to join

  • The study will enroll 50 elderly (≥65 years) previously untreated patient with newly diagnosed MCL.
  • Pathology confirmed diagnosis of mantle cell lymphoma with CD20 positivity and chromosome translocation t (11;14), (q13;q32) and/or positive cyclin D1 in tissue biopsy (See Appendix I, footnote 10). Cyclin D1 negative MCL are allowed after confirming the diagnosis of MCL from hem-path at MDACC.
  • Newly diagnosed elderly MCL (age ≥65 years) with no prior therapy under all risk categories
  • Patients with preexisting well-controlled cardio-vascular comorbidities - patients on anticoagulants (excluding warfarin and vitamin K antagonists), antiplatelet, anti-hypertensive, prior ablation, anti-arrhythmia, prior arrhythmias, baseline EKG abnormalities and cardiology clearance are allowed. Ejection fraction >=50% and cardiology clearance are required. (Echo and EKG and cardiology consultation within 2 months prior to C1D1 are allowed).
  • Willing and able to participate in all required evaluations and procedures in this study protocol, including swallowing capsules and tablets without difficulty.
  • Ability to understand the purpose and risks of the study and provide signed and dated informed consent and authorization to use protected health information (in accordance with national and local patient privacy regulations).
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  • Bi-dimensional measurable disease using the Cheson criteria (Measurable disease by PET-CT scan defined as at least 1 lesion that measures ≥ 1.5 cm in single dimension.) Gastrointestinal, bone marrow or spleen only patients are allowable.
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2 with no deterioration over the previous 2 weeks prior to baseline or day of first dosing.
  • An absolute neutrophil count (ANC) > 1,000/mm3 and platelet count >100,000/mm3 (Patients who have bone marrow and spleen infiltration by MCL are eligible, the ANC and platelets counts will not be limited).
  • Serum bilirubin <1.5 mg/dl and creatinine clearance minimum to 50 mL/min per the Cockcroft-Gault formula (Appendix VII)
  • AST (SGOT) and ALT (SGPT) < 2. x upper limit of normal or < 5 x upper limit of normal if hepatic metastases are present. Gilbert's disease is allowed.
  • Disease free of prior malignancies with exception of currently treated basal cell, squamous cell carcinoma of the skin, carcinoma "in situ" of the cervix or breast, or other malignancies in remission (including prostate cancer patients in remission from radiation therapy, surgery or brachytherapy), not actively being treated with life expectancy of > 3 years. PI can use clinical judgement in the best interest of patients.
  • WOBP and males must be willing to use highly effective methods of birth control. therapy. Woman of childbearing potential (WOCBP) who are sexually active must use highly effective methods of contraception during treatment and for 2 days after the last dose of acalabrutinib tablet and for 12 months following the last dose of rituximab. For male subjects with a pregnant or non-pregnant WOCBP partner, should use barrier contraception, during treatment and for 2 days after the last dose of acalabrutinib and for 1 month following the last dose of rituximab even if they have had a successful vasectomy. Male subjects must agree to refrain from sperm donation during the study. (See Appendix VI)

Who cannot join

  • Prior treatment with acalabrutinib or any treatment for MCL.
  • History of prior malignancy that could affect compliance with the protocol or interpretation of results, except for the following:
  • Curatively treated basal cell carcinoma or squamous cell carcinoma of the skin or carcinoma in situ of the cervix or carcinoma in situ of the prostate at any time prior to study.
  • Other cancers not specified above that have been curatively treated by surgery and/or radiation therapy from which subject is disease-free for ≥3 years without further treatment.
  • Patients with central nervous system involvement with mantle cell lymphoma or with suspected or confirmed progressive multifocal leukoencephalopathy (PML) are excluded since those patients have very poor prognosis, need aggressive intensive chemoimmunotherapy and intrathecal chemotherapy along with BTK inhibitors and these patients would not be eligible for this study.
  • Pregnant or breast-feeding females.
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  • Refractory nausea and vomiting, inability to swallow the formulated product, or malabsorption syndrome; chronic gastrointestinal disease, gastric restrictions, or bariatric surgery such as gastric bypass; partial or complete bowel obstruction, or previous significant bowel resection that would preclude adequate absorption, distribution, metabolism, or excretion of study treatment
  • Known history of hypersensitivity or anaphylaxis to study drug(s) including active product or excipient components.
  • Prothrombin time (PT)/INR or aPTT (in the absence of lupus anticoagulant) >2x ULN.
  • Concurrent participation in another therapeutic clinical trial.
  • Immunization with live vaccine within 4 weeks of and during therapy with Rituximab.
  • History of or ongoing confirmed progressive multifocal leukoencephalopathy (PML)
  • Any active significant infection (e.g., bacterial, viral or fungal, including subjects with positive cytomegalovirus [CMV] DNA polymerase chain reaction [PCR]).
  • Serologic status reflecting active hepatitis B or C infection.
  • Subjects who are hepatitis B core antibody (anti-HBc) positive and who are hepatitis B surface antigen (HBsAg) negative will need to have a negative PCR result before randomization and must be willing to undergo DNA PCR testing during the study. Those who are HbsAg-positive or hepatitis B PCR positive will be excluded.
  • Subjects who are hepatitis C antibody positive will need to have a negative PCR result before randomization. Those who are hepatitis C PCR positive will be excluded.13. Major surgical procedure within 30 days before the 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.
  • 14. Patients with HIV/AIDS
  • 15. Active bleeding, history of bleeding diathesis (such as Hemophilia or Von-Willebrand disease), Any history of intracranial bleed or stroke within 6 months of first dose of study drug.
  • 16. Uncontrolled AIHA (autoimmune hemolytic anemia) or ITP (idiopathic thrombocytopenic purpura).
  • 17. Presence of a gastrointestinal ulcer diagnosed by endoscopy within 3 months before first dose of study drug.
  • 18. Major surgical procedure within 30 days before the 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.
  • 19. Requires anticoagulation with warfarin or equivalent vitamin K antagonist.
  • 20. Concomitant use of corticosteroids at > 20 mg prednisone or equivalent per day > 2 weeks.
  • 21. Requires treatment with strong CYP3A inhibitors or inducers (refer to section 8.6.1 and list in Appendix V).
  • 22. Patients who have had a stroke within 6 months.
  • 23. Any of the following conditions considered clinically significant cardiovascular diseases as determined after cardiology consultation: Note: Subjects with controlled, asymptomatic atrial fibrillation can enroll on study.
  • Diagnosed Congestive heart failure,
  • Active/symptomatic coronary artery disease
  • Congestive heart failure
  • Myocardial infarction in the preceding 6 months,
  • Significant conduction abnormalities, including but not limited to:
  • o Left bundle branch block,
  • o 2nd degree AV block type II,
  • o 3rd degree block,
  • o QT prolongation (QTc > 480 msec),
  • o Sick sinus syndrome
  • o Ventricular tachycardia
  • Symptomatic bradycardia (heart rate < 50 bpm),
  • Persistent, controlled and uncontrolled atrial fibrillation.
  • Uncontrolled hypertension
  • Hypotension,
  • light headedness and syncope,
  • 24. Active infection
  • 25. Acute infection requiring systemic anti-microbial treatment (systemic antibiotics, antivirals, or antifungals) within 14 days prior to initiation of therapy.
  • 26. Active infection including systemic fungal or CMV infection who were hospitalized in past 6 months.
  • 27. Any other serious medical condition including, but not limited to, uncontrolled diabetes mellitus, uncontrolled thyroid disorder, uncontrolled hypertension i.e. Uncontrolled BP - >160/110 despite 3 different classes of full dose anti-hypertensives medications and in spite of cardiology evaluation. Documentation from cardiology is required to say that the BP is uncontrollable.), COPD, renal failure, psychiatric illness or social circumstances that, in the investigator's opinion places the patient at unacceptable risk and would prevent the subject from signing the informed consent form or complying with study procedures.

Trial locations and contacts

1 site in 1 country.

United States1 site

  • M D Anderson Cancer Center

    Houston, Texas, 77030

Other trials in United States

About this study

Official title: A Phase II Study of Acalabrutinib Plus Rituximab in Previously Untreated Elderly Patients With Mantle Cell Lymphoma

This phase II trial studies the side effects of acalabrutinib and rituximab and its effect in treating patients with previously untreated mantle cell lymphoma. Acalabrutinib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Rituximab is a monoclonal antibody that binds to a protein called CD20, which is found on B-cells, and may kill cancer cells. Giving acalabrutinib and rituximab may help to control mantle cell lymphoma in elderly patients.

Read the detailed description

PRIMARY OBJECTIVES:

  1. To determine the efficacy measured by complete remission (CR) rate of the acalabrutinib in combination with rituximab in newly diagnosed elderly mantle cell lymphoma (MCL) patients.

II. To determine the safety profile of acalabrutinib with rituximab combination in elderly patients with MCL.

SECONDARY OBJECTIVES:

  1. To evaluate the overall response (OR) rate. II. To evaluate the progression-free survival and overall survival. III. To assess serial minimal residual disease (MRD) using clonoseq, circulating tumor deoxyribonucleic acid (ct-DNA) based serial clonal evolution.

IV. Perform baseline genomic profiling for recognizing the predictive signature for response, serial MCL specific analytes assessments while on therapy.

EXPLORATORY OBJECTIVES:

  1. Clonal evolution with targeted sequencing (seq) on ctDNA samples in sequential samples using a MCL specific customized gene panel would be assessed.

II. MRD assay using IgH clonoseq and ctDNA analysis, flow cytometry at various time points from peripheral blood (PB)/bone marrow (BM).

III. Sequential immunologic studies with cytokines/chemokines using a analyte panel, T cell numbers, and immunoglobulins (Ig).

IV. Tissue microenvironmental studies with simultaneous assessment of PB, BM and lymph nodes for gene expression profiling (GEP), single cell seq, ribonucleic acid (RNA) seq and clonal heterogeneity and the impact of acalabrutinib (A)-rituximab (R) treatment.

  1. Extensive bioinformatics studies. VI. Identification of signaling pathways or biomarkers that predict sensitivity after therapy.

OUTLINE:

Patients receive acalabrutinib orally (PO) twice daily (BID) on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also receive rituximab intravenously (IV) over 3-4 hours on days 1, 8, 15, and 22 of cycle 1, and day 1 of cycles 2-12, 14, 16, 18, 20, 22 and 24. Cycles repeats every 28 days for up to 24 months or until complete remission is achieved in the absence of disease progression or unacceptable toxicity.

After completion of study intervention, patients are followed up at 30 days for 1 year, every 4 months for 2 years, every 6 months for 2 years, and then annually for 3 years.

Being tested
Acalabrutinib, Rituximab
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, Calquence

    Given PO

  • RituximabBiological

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

    Given IV

Study groups in NCT04765111
Study groupRoleWhat they receive
Treatment (acalabrutinib, rituximab)ExperimentalPatients receive acalabrutinib PO BID on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also receive rituximab IV over 3-4 hours on days 1, 8, 15, and 22 of cycle 1, and day 1 of cycles 2-12, 14, 18, 20, 22, and 24. Cycles repeats every 28 days for up to 24 months or until complete remission is achieved in the absence of disease progression or unacceptable toxicity.
Receives: Drug: Acalabrutinib; Biological: Rituximab

What is being measured

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

  1. Complete remission rate

    Measured: At 16 weeks

  2. Incidence of adverse events (AEs)

    Toxicity is defined as all related grade 3 or higher AEs and not only the non-hematologic AEs will be considered toxicities treatment-related grade 3 or higher AEs within the first three cycles, and any treatment-related toxicities, which cause drug delays for more than 4 weeks. Toxicity data by type and severity will be summarized by frequency tables for all patients by Common Terminology Criteria for Adverse Events version 5.0.

    Measured: Up to 30 days following the last dose of study drug

Secondary outcomes (3)

  1. Overall response rate

    Summary statistics including mean, standard deviation, median, and range for continuous variables, frequency count and percentage categorical variables will be reported. Complete response rate and its posterior credibility interval will be calculated. Response rate and its 95% confidence interval will be estimated. Logistic regression model may be fitted to assess the effects of important patient prognostic factors on response.

    Measured: Up to 7 years

  2. Progression free survival (PFS)

    Estimated using Kaplan and Meier method. The log-rank test will be used to evaluate the difference in PFS between patient groups.

    Measured: From the start of the treatment to progression or death due to any cause whichever happened first, assessed up to 7 years

  3. Overall survival (OS)

    Estimated using Kaplan and Meier method. The log-rank test will be used to evaluate the difference in OS between patient groups.

    Measured: From the start of the treatment to death due to any cause, assessed up to 7 years

Timeline

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

  1. First posted21 Feb 2021
  2. Study start30 Jun 2021
  3. Primary completion30 Aug 2028 (estimated)
  4. Study completion30 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
53 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04765111
Sponsor's protocol ID
2020-0858
Other IDs
NCI-2021-00538, 2020-0858
Status last verified
Aug 2026
First submitted
18 Feb 2021
Last updated
7 Aug 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Acalabrutinib and Rituximab in people with Mantle Cell Lymphoma, run by M.D. Anderson Cancer Center at 1 site 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 13 inclusion and 46 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 7 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 1 site 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?

This study is still under way. Results are not available in the source record yet.

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?

Complete remission rate (time frame: At 16 weeks). The study lists 2 primary outcomes in all. 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 NCT04765111.

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 7 Aug 2026.

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