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

• Status: Not yet recruiting
• Trial end date: 2025-01-31
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 1/Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Jonsson Comprehensive Cancer Center
• Collaborator: AstraZeneca
• Treatments: Acalabrutinib

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