Acalabrutinib for the Treatment of Ibrutinib-Intolerant Mantle Cell Lymphoma

NCT04189757 | Active Not Recruiting Phase 2 FDA Drug

• 2 other identifiers: 2019-0421NCI-2019-07927
• Study Type: interventional
• Target: 9
• Locations: 1 country
• Sites: 1

Brief Summary

This phase II trial studies how well acalabrutinib works in treating patients with mantle cell lymphoma that cannot tolerate ibrutinib. Acalabrutinib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth.

Conditions

Mantle Cell Lymphoma

Outcome Measures

Primary Outcomes (1)

• Overall response rate (complete response + partial response)

  The primary end point will be met if \> 50% patients attain response (half of patients responding without intolerance). Logistic regression may be utilized to assess the effect of patient prognostic factors on the response rate. Intent-to-treat analysis will be applied to the eligible patients.

  At the end of cycle 3 (each cycle is 28 days)

Secondary Outcomes (3)

• Incidence of adverse events

  At the end of cycle 3 (each cycle is 28 days)

• Progression free survival

  Up to 6 years

• Overall survival

  Up to 6 years

Study Arms (1)

Treatment (acalabrutinib)

EXPERIMENTAL

Patients receive acalabrutinib PO BID on days 1-28. Treatment repeats every 28 days for up to 36 cycles in the absence of disease progression or unacceptable toxicity.

Drug: Acalabrutinib

Interventions

Acalabrutinib DRUG

Given PO

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

Treatment (acalabrutinib)

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 mantle cell lymphoma with CD20 positivity and chromosome translocation t(11;14), (q13;q32) and/or overexpress cyclin D1 in tissue biopsy
• Include patients who require treatment (versus watch/wait)
• Prior treatment with ibrutinib discontinued for reasons other than progression
• Ibrutinib intolerance is defined as unacceptable toxicity where, in the opinion of the investigator, treatment should be discontinued in spite of optimal supportive care as a result of one of the following:
• or more grade \>= 2 non-hematological toxicities; OR
• or more grade 3 \>= 3 non-hematological toxicity; OR
• or more grade 3 neutropenia with infection or fever; OR,
• Grade 4 hematologic toxicity which persists to the point that the investigator chose to stop therapy due to toxicity NOT progression
• Toxicity must have resolved to =\< grade 1 prior to acalabrutinib dosing
• Understand and voluntarily sign an Institutional Review Board (IRB)-approved informed consent form
• Bi-dimensional measurable disease using the Cheson criteria (measurable disease by positron emission tomography \[PET\]-computed tomography \[CT\] 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 2 or less
• Absolute neutrophil count (ANC) \> 1,000/mm\^3
• Patients who have bone marrow infiltration by mantle cell lymphoma (MCL) are eligible if their ANC is \>= 500/mm\^3 (growth factor allowed) or their platelet level is equal to or \> 20,000/mm\^3. These patients should be discussed with either the principal investigator (PI) or co-PI of the study for final approval
• Platelet count \> 75,000/mm\^3

You may not qualify if:

• Prior treatment with acalabrutinib
• History of BTK mutations conferring resistance to BTK inhibitors. Known mutations in the BTK gene that confer resistance to ibrutinib in mantle cell lymphoma include (e.g. BTK C481S, C481R mutations)
• Progressive disease while on ibrutinib therapy. Patients who progressed while on ibrutinib therapy will be excluded from the study, patients who discontinue ibrutinib due to anaphylaxis or hypersensitivity reaction related to ibrutinib will be excluded from participation in the study
• Known history of drug-specific hypersensitivity or anaphylaxis to ibrutinib (including active product or excipient components)
• Pregnant or breast-feeding females
• Patients with active hepatitis B infection. Those with prior hepatitis (hep)-B vaccination (i.e., anti-HBs antibody positive) or natural immunity as evidenced by the presence of anti-HBs and anti-HBc positivity are eligible to enroll. (Known hepatitis C infection is allowed as long as there is no active disease and is cleared by gastrointestinal \[GI\] consultation)
• 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 single agent acalabrutinib as proposed in this study
• 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
• Uncontrolled AIHA (autoimmune hemolytic anemia) or ITP (idiopathic thrombocytopenic purpura)
• Ongoing adverse events from prior ibrutinib therapy (except persistent hematologic toxicity if meeting entry criteria). The PI should determine if AEs are an ongoing sequel of prior BTK therapy such as fungal infections, skin rash, diarrhea, fatigue, cramps and colitis or if the patient has resolved AE and is free of these adverse events \>= 2 months after stopping ibrutinib)
• Malabsorption syndrome, disease significantly affecting gastrointestinal 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 gastrointestinal condition that could interfere with the absorption and metabolism of acalabrutinib
• Presence of a gastrointestinal ulcer diagnosed by endoscopy within 3 months before first dose of study drug
• Major surgery within 4 weeks of initiation of therapy
• Requires anticoagulation with warfarin or equivalent vitamin K antagonist
• Concomitant use of corticosteroids at \> 10 mg prednisone or equivalent per day

Sponsors & Collaborators

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

Study Sites (1)

M D Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Links

• University of Texas MD Anderson Cancer Center Website

MeSH Terms

Conditions

Lymphoma, Mantle-Cell

Interventions

acalabrutinib

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: December 3, 2019
• First Posted: December 6, 2019
• Study Start: August 7, 2020
• Primary Completion (Estimated): June 30, 2027
• Study Completion (Estimated): June 30, 2027
• Last Updated: April 16, 2026

Record last verified: 2026-04

Locations

US (1)