Acalabrutinib Maintenance for the Treatment of Patients With Large B-cell Lymphoma

NCT05256641 | Recruiting Phase 1 DMC FDA Drug

• 2 other identifiers: 21-000979NCI-2021-12421
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 3

Brief Summary

This phase Ib/II trial studies the side effects and efficacy of maintenance acalabrutinib following cellular therapy in treating patients with large B-cell lymphoma at very high risk of the cancer coming back. Acalabrutinib is a small molecular inhibitor that may interfere with the ability of cancer cells to grow and spread.

Conditions

Secondary Central Nervous System Lymphoma; Diffuse Large B-Cell Lymphoma; High-grade B-cell Lymphoma; Transformed Lymphoma

Outcome Measures

Primary Outcomes (1)

• Permanent discontinuation of acalabrutinib

  Tolerability will be determined by the number of patients who permanently discontinue acalabrutinib within 12 months from cellular therapy due to intolerance. The proportion of patients with acalabrutinib discontinuation will be reported along with 95% and 90% confidence intervals.

  Up to 12 months from cellular therapy

Secondary Outcomes (8)

• Progression-free survival (PFS)

  At 12 months from cellular therapy

• PFS

  Up to 5 years

• Overall survival

  Up to 5 years

• Rate of conversion from partial response following chimeric antigen receptor (CAR) T-cell therapy to complete response after the addition of acalabrutinib maintenance

  Up to day 365

• Incidence of dose reductions, interruptions, or discontinuations of acalabrutinib based on the protocol criteria

  Up to day 365

Other Outcomes (4)

• CAR T-cell persistence

  Up to 5 years

• Immunophenotyping of peripheral blood mononuclear cells

  Up to 5 years

• Intracellular cytokine and phospho-protein profiling of peripheral blood mononuclear cells

  Up to 5 years

Study Arms (3)

Group I (acalabrutinib)

EXPERIMENTAL

Beginning day 90, patients receive acalabrutinib PO QD and then PO BID once no longer on prophylactic antifungal (CYP34A inhibitors) until day 365 in the absence of disease progression or unacceptable toxicity.

Drug: Acalabrutinib

Group II (acalabrutinib)

EXPERIMENTAL

Beginning day 60, patients receive acalabrutinib PO QD and then PO BID from day 74 if there are no dose reductions until day 365 in the absence of disease progression or unacceptable toxicity.

Drug: Acalabrutinib

Group III (acalabrutinib)

EXPERIMENTAL

Beginning anytime between days 28-104, patients receive acalabrutinib PO BID until day 365 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

Group I (acalabrutinib); Group II (acalabrutinib); Group III (acalabrutinib)

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Ages 18-70 years
• One of the following:
• Patients undergoing autologous stem cell transplantation (ASCT) or any Food and Drug Administration (FDA)-approved chimeric antigen receptor (CAR) T-cell therapy product for:
• High grade B-cell lymphoma (double or triple hit) with rearrangements in bcl-2 and/or bcl-6, and rearrangement in myc
• Large B-cell lymphoma with a history of secondary CNS involvement
• Histologic transformation of indolent lymphoma to large B-cell lymphoma, including marginal zone lymphoma, follicular lymphoma, chronic lymphocytic leukemia (CLL), small lymphocytic lymphoma (SLL), lymphoplasmacytic leukemia, or Waldenstrom macroglobulinemia
• High risk international prognostic index (IPI) score 4 or 5, at diagnosis or prior to CAR T-cell leukapheresis
• Patients undergoing allogeneic hematopoietic cell transplantation (alloHCT) for large B-cell lymphoma
• Eastern Cooperative Oncology Group (ECOG) 0-2
• Requirements for post-ASCT and post-alloHCT participants:
• Disease status of partial response (PR) or complete response (CR) prior to transplantation
• Receive reduced-intensity conditioning regimen
• Enrollment no later than day +90
• Requirements for post-CAR T-cell therapy participants:
• Disease status of PR or CR after post-CAR T-cell therapy positron emission tomography (PET)-computed tomography (CT) at 1-3 months

You may not qualify if:

• Cord blood as donor source in alloHCT
• New York Heart Association Class III or IV
• Left ventricular ejection fraction \< 50%
• Estimated glomerular filtration rate \< 30 mL/min
• Concurrent long-term use of posaconazole or other strong CYP3A4 inhibitors and unable to replace with equivalent medication
• Acute or chronic graft-versus-host disease (GvHD) \>= stage 3 at time of enrollment
• Received packed red blood cells (pRBC) transfusion within the past 2 weeks
• Received platelet transfusion within the past 1 week
• Active invasive fungal infection
• Active bacterial or viral infection until resolution of the infection
• History of or ongoing confirmed progressive multifocal leukoencephalopathy (PML)
• Received any investigational drug within 30 days or 5 half-lives (whichever is shorter) before first dose of study drug
• 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
• 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
• Received a live virus vaccination within 28 days of first dose of study drug

Sponsors & Collaborators

• Jonsson Comprehensive Cancer Center: lead
• AstraZeneca: collaborator

Study Sites (3)

UCLA / Jonsson Comprehensive Cancer Center

Los Angeles, California, 90095, United States

RECRUITING

University of California Davis Comprehensive Cancer Center

Sacramento, California, 95817, United States

RECRUITING

University of Oklahoma

Oklahoma City, Oklahoma, 73190, United States

NOT YET RECRUITING

MeSH Terms

Conditions

Lymphoma, Large B-Cell, Diffuse

Interventions

acalabrutinib

Condition Hierarchy (Ancestors)

Lymphoma, B-Cell; Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Study Officials

• Caspian Oliai, MD

  UCLA / Jonsson Comprehensive Cancer Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Vlad Kustanovitch

CONTACT

310-206-5756; VKustanovich@mednet.ucla.edu

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 4, 2022
• First Posted: February 25, 2022
• Study Start: January 23, 2023
• Primary Completion (Estimated): January 31, 2027
• Study Completion (Estimated): January 31, 2028
• Last Updated: March 10, 2026

Record last verified: 2026-03

Locations

US (3)