Using acalabrutinib to prevent relapse in patients with large B-cell lymphoma

Acalabrutinib Maintenance Following Cellular Therapy for Large B-Cell Lymphoma Patients at Very High Risk for Relapse

This study is testing if the drug acalabrutinib can help prevent cancer from coming back in patients with large B-cell lymphoma who are at high risk after treatment.

Quick facts

• Phase: PHASE1; PHASE2
• Study type: Interventional
• Enrollment: 24 (estimated)
• Ages: 18 Years to 70 Years
• Sex: All
• Sponsor: Jonsson Comprehensive Cancer Center (other)
• Drugs / interventions: acalabrutinib, CAR T, chimeric antigen receptor, CAR-T
• Locations: 3 sites (Los Angeles, California and 2 other locations)
• Trial ID: NCT05256641 on ClinicalTrials.gov

What this trial studies

This trial investigates the safety and effectiveness of acalabrutinib as a maintenance therapy for patients with large B-cell lymphoma who are at very high risk of cancer recurrence after cellular therapy. It aims to assess the drug's tolerability, the durability of remission, and overall survival rates. Additionally, the study will evaluate the conversion rates from partial to complete response following treatment and monitor for any adverse effects. The trial includes both phase Ib and phase II components to gather comprehensive data on the drug's impact.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18-70 with high-risk large B-cell lymphoma undergoing cellular therapy.

Not a fit: Patients with low-risk lymphoma or those not undergoing cellular therapy may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could significantly reduce the risk of relapse in patients with large B-cell lymphoma.

How similar studies have performed: Other studies have shown promising results with similar maintenance therapies, suggesting potential for success in this approach.

Eligibility criteria

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

Where this trial is running

Los Angeles, California and 2 other locations

• UCLA / Jonsson Comprehensive Cancer Center — Los Angeles, California, United States (RECRUITING)
• University of California Davis Comprehensive Cancer Center — Sacramento, California, United States (RECRUITING)
• University of Oklahoma — Oklahoma City, Oklahoma, United States (NOT_YET_RECRUITING)

Study contacts

• Principal investigator: Caspian Oliai, MD — UCLA / Jonsson Comprehensive Cancer Center
• Study coordinator: Vlad Kustanovitch

Conditions: Diffuse Large B-Cell Lymphoma, High-grade B-cell Lymphoma, Transformed Lymphoma, Secondary Central Nervous System Lymphoma