Recruiting
Phase 1
Phase 2

Acalabrutinib

Sponsor:

Jonsson Comprehensive Cancer Center

Code:

NCT05256641

Conditions

Diffuse Large B-Cell Lymphoma

High-grade B-cell Lymphoma

Transformed Lymphoma

Secondary Central Nervous System Lymphoma

Eligibility Criteria

Sex: All

Age: 18 - 70

Healthy Volunteers: Not accepted

Interventions

Acalabrutinib

Study Details

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

Diffuse Large B-Cell Lymphoma

High-grade B-cell Lymphoma

Transformed Lymphoma

Secondary Central Nervous System Lymphoma

Study ID

NCT05256641

Start date

Jan 23, 2023

Status verified date

Mar, 2026

Completion date

Jan 31, 2028

Anticipated

Primary completion date

Jan 31, 2027

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 18 - 70

Healthy Volunteers: Not accepted

Inclusion Criteria:

  • 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
  • Enrollment no later than day +104
  • Ability to give full informed consent
  • Female subjects who are sexually active and can bear children must agree to use highly effective forms of contraception while on the study and for 2 days after the last dose of acalabrutinib
  • Willing and able to participate in all required evaluations and procedures in this study protocol, including swallowing capsules and tablets without difficulty
  • Absolute neutrophil count (ANC) > 500/uL (microliters)
  • Platelets > 50,000/uL independent of transfusions
  • Hemoglobin > 8 g/dL independent of transfusions
  • Serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 3 x upper limit of normal (ULN)
  • Total bilirubin =< 1.5 x ULN, unless directly attributable to Gilbert's syndrome
  • Creatinine clearance >= 60 mL/min based on Cockcroft-Gault glomerular filtration rate (GFR) and serum creatinine (Cr) =< 1.8 mg/dL

Exclusion Criteria:

  • 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
  • Known history of infection with human immunodeficiency virus (HIV)
  • History of bleeding diathesis (e.g., hemophilia, von Willebrand disease)
  • Requires or receiving anticoagulation with warfarin or equivalent vitamin K antagonists
  • Requires treatment with a strong cytochrome P450 3A (CYP3A) inhibitor or inducer. The use of strong CYP3A inhibitors within 1 week or strong CYP3A inducers within 3 weeks of the first dose of study drug is prohibited
  • Breastfeeding or pregnant
  • Concurrent participation in another therapeutic clinical trial

Study Design

Enrollment

24 participants

Anticipated

Allocation

Non randomized

Intervention Model

Parallel Assignment

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: Group I (acalabrutinib)

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.

experimental: Group II (acalabrutinib)

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.

experimental: Group III (acalabrutinib)

Beginning anytime between days 28-104, patients receive acalabrutinib PO BID until day 365 in the absence of disease progression or unacceptable toxicity.

Interventions

Acalabrutinib

Given PO

Primary outcome measure

  • Permanent discontinuation of acalabrutinib [ Time Frame: Up to 12 months from cellular therapy ]

Central Contacts and Locations

Central contacts

Vlad Kustanovitch

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

Locations

UCLA / Jonsson Comprehensive Cancer Center

Recruiting

Los Angeles, California, United States, 90095

Contacts

Vlad Kustanovich

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

Principal Investigator:

Caspian Oliai, MD

University of California Davis Comprehensive Cancer Center

Recruiting

Sacramento, California, United States, 95817

Contacts

Joseph M. Tuscano

916-734-3772jtuscano@ucdavis.edu

Principal Investigator:

Joseph M. Tuscano

More Information

Sponsor

Jonsson Comprehensive Cancer Center

Last update posted

Mar 10, 2026

Last verified

Mar, 2026

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-08. This information was provided to ClinicalTrials.gov by Jonsson Comprehensive Cancer Center on 2026-03-10.