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

Study Purpose

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.

Recruitment Criteria

Accepts Healthy Volunteers

Healthy volunteers are participants who do not have a disease or condition, or related conditions or symptoms

No
Study Type

An interventional clinical study is where participants are assigned to receive one or more interventions (or no intervention) so that researchers can evaluate the effects of the interventions on biomedical or health-related outcomes.


An observational clinical study is where participants identified as belonging to study groups are assessed for biomedical or health outcomes.


Searching Both is inclusive of interventional and observational studies.

Interventional
Eligible Ages 18 Years - 70 Years
Gender All
More Inclusion & Exclusion 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

Trial Details

Trial ID:

This trial id was obtained from ClinicalTrials.gov, a service of the U.S. National Institutes of Health, providing information on publicly and privately supported clinical studies of human participants with locations in all 50 States and in 196 countries.

NCT05256641
Phase

Phase 1: Studies that emphasize safety and how the drug is metabolized and excreted in humans.

Phase 2: Studies that gather preliminary data on effectiveness (whether the drug works in people who have a certain disease or condition) and additional safety data.

Phase 3: Studies that gather more information about safety and effectiveness by studying different populations and different dosages and by using the drug in combination with other drugs.

Phase 4: Studies occurring after FDA has approved a drug for marketing, efficacy, or optimal use.

Phase 1/Phase 2
Lead Sponsor

The sponsor is the organization or person who oversees the clinical study and is responsible for analyzing the study data.

Jonsson Comprehensive Cancer Center
Principal Investigator

The person who is responsible for the scientific and technical direction of the entire clinical study.

Caspian Oliai, MD
Principal Investigator Affiliation UCLA / Jonsson Comprehensive Cancer Center
Agency Class

Category of organization(s) involved as sponsor (and collaborator) supporting the trial.

Other, Industry
Overall Status Recruiting
Countries United States
Conditions

The disease, disorder, syndrome, illness, or injury that is being studied.

Diffuse Large B-Cell Lymphoma, High-grade B-cell Lymphoma, Transformed Lymphoma, Secondary Central Nervous System Lymphoma
Additional Details

PRIMARY OBJECTIVE:

  • I. To determine the safety and tolerability of maintenance acalabrutinib following cellular therapy in participants with large B-cell lymphoma at very high risk for relapse.
SECONDARY OBJECTIVES:
  • I. To estimate the effectiveness of maintenance acalabrutinib following cellular therapy in participants with large B-cell lymphoma at high risk for relapse.
  • II. To estimate the durability of remission after completion of acalabrutinib maintenance.
  • III. To estimate survival following completion of acalabrutinib maintenance.
  • IV. To estimate the rate of conversion from partial response (PR) following chimeric antigen receptor (CAR) T-cell therapy to complete response (CR) after the addition of acalabrutinib maintenance.
  • V. To estimate rates of dose reductions, dose pauses, and permanent discontinuations of acalabrutinib that occur post-cellular therapy.
  • VI. To estimate the rate of stage >= 2 graft-versus-host disease in participants receiving acalabrutinib post-allogeneic hematopoietic cell transplantation (alloHCT).
  • VII. To estimate the rates of grade 2, 3, and 4 hematologic toxicity in participants receiving acalabrutinib post-cellular therapy.
  • VIII. To estimate the rates of grade 2, 3, and 4 non-hematologic toxicity in participants receiving acalabrutinib post-cellular therapy.
EXPLORATORY OBJECTIVES:
  • I. To evaluate CAR T-cell persistence in the setting of acalabrutinib.
  • II. To evaluate changes in immunophenotype of peripheral blood mononuclear cells before and after initiation of acalabrutinib, and changes at time of relapse.
  • III. To evaluate changes in circulating tumor deoxyribonucleic acid (ctDNA), intracellular cytokine and phospho-protein profiling of peripheral blood mononuclear cells before and after initiation of acalabrutinib, and changes at time of relapse.
  • IV. To determine if there are signs of central nervous system (CNS) penetration of acalabrutinib.
OUTLINE: Patients are assigned to 1 of 3 groups. GROUP I (ALLOHCT GROUP): Beginning day 90, patients receive acalabrutinib orally (PO) once daily (QD) and then( orally, twice daily (PO BID) once no longer on prophylactic antifungal (CYP34A inhibitors) until day 365 in the absence of disease progression or unacceptable toxicity. GROUP II (AUTOLOGOUS STEM CELL TRANSPLANTATION [ASCT] GROUP): 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. GROUP III (CAR-T CELL THERAPY GROUP): Beginning anytime between days 28-104, patients receive acalabrutinib PO BID until day 365 in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up at 30 days.

Arms & Interventions

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

Drug: - Acalabrutinib

Given PO

Contact a Trial Team

If you are interested in learning more about this trial, find the trial site nearest to your location and contact the site coordinator via email or phone. We also strongly recommend that you consult with your healthcare provider about the trials that may interest you and refer to our terms of service below.

Los Angeles, California

Status

Recruiting

Address

UCLA / Jonsson Comprehensive Cancer Center

Los Angeles, California, 90095

Site Contact

Vlad Kustanovich

[email protected]

310-206-5756

Sacramento, California

Status

Recruiting

Address

University of California Davis Comprehensive Cancer Center

Sacramento, California, 95817

Site Contact

Joseph M. Tuscano

[email protected]

916-734-3772

University of Oklahoma, Oklahoma City, Oklahoma

Status

Not yet recruiting

Address

University of Oklahoma

Oklahoma City, Oklahoma, 73190

Site Contact

Matthew J. Wieduwilt

[email protected]

405-217-8001

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