Acalabrutinib and Anti-CD19 CAR T-cell Therapy for the Treatment of B-cell Lymphoma

NCT04257578 | Active Not Recruiting Phase 1 DMC FDA Drug

• 3 other identifiers: RG1006269NCI-2020-0023810418
• Study Type: interventional
• Target: 23
• Locations: 1 country
• Sites: 1

Brief Summary

This phase I/II trial studies the safety of acalabrutinib and axicabtagene ciloleucel in treating patients with B-cell lymphoma. Acalabrutinib may stop the growth of tumor cells by blocking key pathways needed for cell growth. Immunotherapy with axicabtagene ciloleucel is engineered to target a specific surface antigen on lymphoma cells. Acalabrutinib may enhance the efficacy of axicabtagene ciloleucel in treating patients with B-cell lymphoma.

Conditions

B-Cell Non-Hodgkin Lymphoma; Diffuse Large B-Cell Lymphoma, Not Otherwise Specified; High Grade B-Cell Lymphoma; Primary Mediastinal (Thymic) Large B-Cell Lymphoma; Transformed Follicular Lymphoma to Diffuse Large B-Cell Lymphoma; Grade 1 Follicular Lymphoma; Grade 2 Follicular Lymphoma; Grade 3a Follicular Lymphoma

Keywords

Non-Hodgkin Lymphoma

Outcome Measures

Primary Outcomes (1)

• Incidence of adverse events

  Toxicity as defined by the following: grade \>= 3 cytokine release syndrome, grade \>= 3 neurotoxicity within 30 days of infusion of axicabtagene ciloleucel. Grading will be done in accordance with the National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0 for neurotoxicity and the Lee Criteria for cytokine release syndrome, unless otherwise specified.

  Up to 30 days post axicabtagene ciloleucel infusion

Secondary Outcomes (4)

• Complete response rate following chimeric antigen receptor T-cells therapy (CART)

  Up to 5 years post treatment

• Overall survival

  Up to 5 years post treatment

• Progression-free survival

  Up to 5 years post treatment

• Response rate

  Up to 3 weeks

Study Arms (1)

Treatment (acalabrutinib, axicabtagene ciloleucel)

EXPERIMENTAL

Beginning up to 3 weeks and at least 24 hours prior to leukapheresis, patients receive acalabrutinib PO every 12 hours. Treatment continues in the absence of disease progression or unacceptable toxicity. Patients also receive axicabtagene ciloleucel IV at 36-96 hours after completion of lymphodepleting chemotherapy.

Drug: Acalabrutinib; Biological: Axicabtagene Ciloleucel

Interventions

Acalabrutinib DRUG

Given PO

Also known as: 1420477-60-6, ACP-196, Bruton Tyrosine Kinase Inhibitor ACP-196

Treatment (acalabrutinib, axicabtagene ciloleucel)

Axicabtagene Ciloleucel BIOLOGICAL

Given IV

Also known as: KTE C19, KTE-C19, KTE-C19 CAR, Yescarta

Treatment (acalabrutinib, axicabtagene ciloleucel)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically confirmed large B-cell lymphoma, including diffuse large B-cell lymphoma (DLBCL) not otherwise specified, primary mediastinal large B-cell lymphoma, high grade B-cell lymphoma, and DLBCL arising from follicular lymphoma, and indolent (grade 1-3a) FL
• Criteria must be met for receiving commercial axi-cel per Food and Drug Administration (FDA) label
• \>= 18 years of age
• Patients must be capable of understanding and providing a written informed consent
• Negative serum pregnancy test within 2 days of initiating acalabrutinib for women of childbearing potential (WOCBP), defined as those who have not been surgically sterilized or who have not been free of menses for at least 1 year
• Fertile male and WOCBP patients must be willing to use highly effective contraceptive methods before, during, and for at least 4 months after the CAR T-cell infusion or within 2 days of acalabrutinib, whichever is longer
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-1
• Creatine clearance (CrCl) \> 50 mL/min or serum creatinine =\< 2.5
• Total bilirubin =\< 1.5x the upper limit of normal
• Adequate pulmonary function, defined as =\< grade 1 dyspnea and oxygen saturation (SaO2) \>= 92% on room air
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =\< 3x the upper limit of normal
• Adequate cardiac function, defined as left ventricular ejection fraction (LVEF) of \>= 50% and without evidence for pericardial effusion
• At least 1 measurable lesion \>= 15 mm according to the International Working Group consensus response evaluation criteria in lymphoma (Younes 2017)
• HIV POSITIVE COHORT: Human immunodeficiency virus (HIV)-1 or HIV-2 infection, as documented by any federally approved, licensed HIV test
• HIV POSITIVE COHORT: HIV plasma HIV-1 ribonucleic acid (RNA) below detected limit obtained by Food and Drug Administration (FDA)-approved assays within 4 weeks prior to registration

You may not qualify if:

• Active and uncontrolled systemic or clinically significant infection that would contraindicate myelosuppressive therapy or CART infusion
• Patients intolerant of acalabrutinib
• Requires treatment with proton pump inhibitors (eg, omeprazole, esomeprazole, lansoprazole, dexlansoprazole, rabeprazole, or pantoprazole). Note: Subjects receiving proton pump inhibitors who switch to H2-receptor antagonists or antacids are eligible for enrollment to this study
• Patients with detectable cerebrospinal fluid malignant cells, or brain metastases, or with a history of cerebrospinal fluid malignant cells or brain metastases
• History of a seizure disorder, cerebrovascular ischemia/hemorrhage, dementia, cerebellar disease, or any autoimmune disease with central nervous system (CNS) involvement
• Use of a strong CYP3A inhibitor OR inducer within 7 days of starting study drugs or requirement of use of strong CYP3A inhibitor OR inducer at the time of enrollment
• Disease that is known to be refractory to BTK inhibition
• Absolute neutrophil count (ANC) \< 1000/ul
• Platelets \< 50K/ul
• Another active malignancy requiring systemic treatment, unless approved by principal investigator (PI)
• Clinically significant cardiovascular disease such as uncontrolled or symptomatic arrhythmias, congestive heart failure, or myocardial infarction within 6 months of screening, or any class 3 or 4 cardiac disease as defined by the New York Heart Association Functional Classification. Subjects with controlled, asymptomatic atrial fibrillation during screening can enroll on study
• Inability to swallow whole pills, malabsorption syndrome, disease significantly affecting gastrointestinal function, or resection of the stomach or small bowel that is likely to affect absorption, symptomatic inflammatory bowel disease, partial or complete bowel obstruction, or gastric restrictions and bariatric surgery, such as gastric bypass
• Active bleeding, history of bleeding diathesis (eg, hemophilia or von Willebrand disease)
• Uncontrolled AIHA (autoimmune hemolytic anemia) or ITP (idiopathic thrombocytopenic purpura)
• Receiving anticoagulation with warfarin or equivalent vitamin K antagonists (eg, phenprocoumon) within 7 days of first dose of study drug

Sponsors & Collaborators

• University of Washington: lead
• AstraZeneca: collaborator

Study Sites (1)

Fred Hutch/University of Washington Cancer Consortium

Seattle, Washington, 98109, United States

Location

MeSH Terms

Conditions

Lymphoma, B-Cell; Lymphoma, Large B-Cell, Diffuse; Lymphoma, Follicular; Lymphoma, Non-Hodgkin

Interventions

acalabrutinib; axicabtagene ciloleucel

Condition Hierarchy (Ancestors)

Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Study Officials

• Ajay Gopal

  Fred Hutch/University of Washington Cancer Consortium

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 28, 2020
• First Posted: February 6, 2020
• Study Start: December 2, 2020
• Primary Completion: August 7, 2025
• Study Completion (Estimated): March 1, 2031
• Last Updated: October 8, 2025

Record last verified: 2025-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)