RecruitingPhase 1Phase 2NCT05256641

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

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

Sponsor

Jonsson Comprehensive Cancer Center

Enrollment

24 participants

Start Date

Jan 23, 2023

Study Type

INTERVENTIONAL

Conditions

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

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.

Eligibility

Min Age: 18 YearsMax Age: 70 Years

Inclusion Criteria25

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 Criteria21

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