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

NCT04765111 | Active Not Recruiting Phase 2 DMC FDA Drug

• 2 other identifiers: 2020-0858NCI-2021-00538
• Study Type: interventional
• Target: 53
• Locations: 1 country
• Sites: 1

Brief 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. 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.

Conditions

Mantle Cell Lymphoma

Outcome Measures

Primary Outcomes (2)

• Complete remission rate

  At 16 weeks

• 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.

  Up to 30 days following the last dose of study drug

Secondary Outcomes (3)

• Overall response rate

  Up to 7 years

• Progression free survival (PFS)

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

• Overall survival (OS)

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

Study Arms (1)

Treatment (acalabrutinib, rituximab)

EXPERIMENTAL

Patients 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.

Drug: Acalabrutinib; Biological: Rituximab

Interventions

Acalabrutinib DRUG

Given PO

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

Treatment (acalabrutinib, rituximab)

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, Rituxan, Rituximab ABBS, 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-abbs, RTXM83, Truxima

Treatment (acalabrutinib, rituximab)

Eligibility Criteria

• Age: 65 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Older Adult (65+)

You may qualify if:

• 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).
• 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)

You may not qualify if:

• 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:
• a. 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.
• b. 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.
• 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.

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead

Study Sites (1)

M D Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Links

• MD Anderson Cancer Center

MeSH Terms

Conditions

Lymphoma, Mantle-Cell

Interventions

acalabrutinib; Rituximab; CT-P10

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)

Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Luhua (Michael) Wang

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

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: February 18, 2021
• First Posted: February 21, 2021
• Study Start: June 30, 2021
• Primary Completion (Estimated): August 30, 2026
• Study Completion (Estimated): August 30, 2026
• Last Updated: May 20, 2026

Record last verified: 2026-05

Locations

US (1)