Venetoclax and Acalabrutinib in Treating Patients With Relapsed or Refractory Mantle Cell Lymphoma

NCT03946878 | Active Not Recruiting Phase 2 FDA Drug

• 2 other identifiers: 2018-0935NCI-2019-02354
• Study Type: interventional
• Target: 32
• Locations: 1 country
• Sites: 1

Brief Summary

This phase II trial studies how well venetoclax and acalabrutinib work in treating patients with mantle cell lymphoma that did not respond to previous treatment or has come back. Venetoclax may cause cancer cell death by blocking the mechanism that cancer cells use to stay alive. Acalabrutinib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Giving venetoclax and acalabrutinib together may kill more cancer cells in patients with mantle cell lymphoma.

Conditions

Pleomorphic Variant Mantle Cell Lymphoma; Recurrent Mantle Cell Lymphoma; Refractory Mantle Cell Lymphoma; Blastoid Variant Mantle Cell Lymphoma; CCND1 Protein Overexpression; CD20 Positive; CD5 Positive; FCER2 Negative; t(11;14)(q13;q32)

Outcome Measures

Primary Outcomes (1)

• Complete response (CR)

  Assessed by Lugano criteria - positron emission tomography (PET)-computed tomography, and in a subset of patients by bone marrow flow cytometry, circulating tumor deoxyribonucleic acid and endoscopy if at baseline there is gut involvement. Response will be calculated separately with and without knowledge of the PET result by International Working Group criteria, in order to provide context in relation to historical control data. Will estimate the CR along with the 95% credible interval.

  16 weeks

Secondary Outcomes (6)

• Overall response rate

  5 years

• Duration of response

  5 years

• Event free survival

  5 years

• Progression free survival

  5 years

• Overall survival

  5 years

Study Arms (1)

Treatment (acalabrutinib, venetoclax)

EXPERIMENTAL

Patients receive acalabrutinib PO BID on days 1-28. Starting cycle 2 day 1, patients also receive venetoclax PO daily. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Drug: Acalabrutinib; Drug: Venetoclax

Interventions

Acalabrutinib DRUG

Given PO

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

Treatment (acalabrutinib, venetoclax)

Venetoclax DRUG

Given PO

Also known as: ABT-0199, ABT-199, ABT199, GDC-0199, RG7601, Venclexta

Treatment (acalabrutinib, venetoclax)

Eligibility Criteria

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

You may qualify if:

• Confirmed diagnosis of MCL in previously treated relapsed/refractory patients with/without chromosome translocation t(11;14), (q13;q32) by FISH and/or overexpress cyclin D1 in tissue biopsy (blastoid/pleomorphic morphology, complex karyotype is acceptable), cyclin D1 negative mantle cell lymphoma is allowed. MCL diagnosis confirmation is needed by pathologist.
• Disease had relapsed after or been refractory to \>= 1 prior therapy for MCL and now requires further treatment.
• Ability to understand the purpose and risks of the study and provide signed and dated Institutional Review Board (IRB) approved informed consent and authorization to use protected health information (in accordance with national and local patient privacy regulations).
• Willing and able to participate in all required evaluations and procedures in this study protocol, including swallowing capsules and tablets without difficulty.
• Age ≥ 18 years at the time of signing the ICF.
• Bi-dimensional measurable disease using the Cheson criteria (measurable disease by computed tomography \[CT\] scan defined as at least 1 lesion that measures \>= 1.5 cm in single dimension). Gastrointestinal (GI), 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. The following laboratory criteria must be met
• Absolute neutrophil count (ANC) \> 1,000/mm\^3 independent of growth factor support.
• Platelet count \>= 100,000/mm\^3 or \>= 50,000/mm\^3 if bone marrow involved with lymphoma, independent of transfusion support in either situation.
• Creatinine (Cr) =\< 2 or Cr clearance \>= 30 mL/min.
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) \< 3 x upper limit of normal (ULN), serum bilirubin \< 1.5 mg/dl, unless due to Gilbert's syndrome, documented liver involvement with lymphoma, or of non-hepatic origin.
• Prothrombin time (PT)/international normalized ratio (INR) =\< 1.5 x ULN and partial thromboplastin time (PTT) =\< 1.5 x ULN.
• Disease free of prior malignancies other than MCL 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. Principal investigator (PI) can use clinical judgement in the best interest of patients.
• Females of childbearing potential (FCBP) must have a negative serum or urine pregnancy test and willing to use highly effective methods of birth control.
• Male subjects must agree to refrain from sperm donation during the study.

You may not qualify if:

• Prior treatment with acalabrutinib or any investigational drug within 30 days or 5 half-lives (whichever is shorter) before first dose of study drug.
• 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.
• Any serious medical condition including but not limited to, uncontrolled hypertension, uncontrolled diabetes mellitus, active/symptomatic coronary artery disease, chronic obstructive pulmonary disease, renal failure, active hemorrhage, or psychiatric illness that, in the investigator's opinion places the patient at unacceptable risk and would prevent the subject from signing the ICF.
• Pregnant or breast-feeding females.
• Known human immunodeficiency virus (HIV) infection.
• Uncontrolled autoimmune hemolytic anemia (AIHA) or idiopathic thrombocytopenic purpura (ITP). 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.
• a. 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. b. 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.
• Central nervous system (CNS) disease with serious significance.
• Refractory nausea and vomiting, inability to swallow the formulated product, or Malabsorption syndrome, disease significantly affecting GI function, or resection of the stomach or small bowel or ulcerative colitis, symptomatic inflammatory bowel disease, or partial or complete bowel obstruction, or any other GI condition that could interfere with the absorption metabolism, and excretion of acalabrutinib or venetoclax.
• 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.
• Known bleeding diathesis (e.g., von Willebrand's disease) or hemophilia.

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead
• National Cancer Institute (NCI): collaborator

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; venetoclax

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

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: May 9, 2019
• First Posted: May 13, 2019
• Study Start: August 13, 2019
• Primary Completion (Estimated): February 8, 2028
• Study Completion (Estimated): February 8, 2028
• Last Updated: February 17, 2026

Record last verified: 2026-02

Locations

US (1)