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

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ClinicalTrials.gov Identifier: NCT04257578
Recruitment Status : Recruiting
First Posted : February 6, 2020
Last Update Posted : December 13, 2022
Information provided by (Responsible Party):
University of Washington

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.

Condition or disease Intervention/treatment Phase
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 Drug: Acalabrutinib Biological: Axicabtagene Ciloleucel Phase 1 Phase 2

Detailed Description:


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

After completion of study treatment, patients are followed up every 3 months for up to 5 years.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 50 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Acalabrutinib in Combination With Anti-CD19 Chimeric Antigen Receptor T-Cells (CART) in B-Cell Lymphoma
Actual Study Start Date : December 2, 2020
Estimated Primary Completion Date : March 1, 2024
Estimated Study Completion Date : March 1, 2029

Arm Intervention/treatment
Experimental: Treatment (acalabrutinib, axicabtagene ciloleucel)
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
Given PO
Other Names:
  • 1420477-60-6
  • ACP-196
  • Bruton Tyrosine Kinase Inhibitor ACP-196

Biological: Axicabtagene Ciloleucel
Given IV
Other Names:
  • KTE C19
  • KTE-C19
  • KTE-C19 CAR
  • Yescarta

Primary Outcome Measures :
  1. Incidence of adverse events [ Time Frame: Up to 30 days post axicabtagene ciloleucel infusion ]
    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.

Secondary Outcome Measures :
  1. Complete response rate following chimeric antigen receptor T-cells therapy (CART) [ Time Frame: Up to 5 years post treatment ]
    Will be assessed per Lugano criteria.

  2. Overall survival [ Time Frame: Up to 5 years post treatment ]
  3. Progression-free survival [ Time Frame: Up to 5 years post treatment ]
  4. Response rate [ Time Frame: Up to 3 weeks ]
    Will assess response rate (complete response + partial response + stable response) following bridging prior to CART.

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • 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 Inclusion Criteria:

  • HIV-1 or HIV-2 infection, as documented by any federally approved, licensed HIV test
  • HIV plasma HIV-1 RNA below detected limit obtained by FDA-approved assays within 4 weeks prior to registration
  • CD4 cell count greater than 200 cells/mm3 obtained within 2 weeks prior to enrollment at any U.S. laboratory that has a clinical laboratory improvement amendments (CLIA) certification or its equivalent
  • Anti-retroviral treatment (ART) should be initiated > 4 weeks prior to study drug so that toxicity assessment of ART is separated from study drug. If patient is on an ART regimen that contains a strong CYP3A inhibitor (e.g ritonavir and cobicistat) or CYP3A inducer (e.g. efavirenz), changes in ART therapy should be considered in collaboration with HIV provider
  • No acute active HIV-associated opportunistic infection requiring antibiotic treatment
  • No uncontrolled systemic fungal, bacterial, viral, or other infection
  • Hemoglobin > 8.0 g/dl
  • Serum creatinine < 1.5 mg/dL OR creatinine clearance >60 mL/minAST and ALT < 2.5 x ULN

Exclusion Criteria:

  • 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
  • Prothrombin time/international normalized ratio (INR) or activated partial thromboplastin time (aPTT) (in the absence of Lupus anticoagulant) > 2 x upper limit of normal (ULN)
  • History of significant cerebrovascular disease or event, including stroke or intracranial hemorrhage, within 6 months before the first dose of study drug
  • Major surgical procedure within 7 days of 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
  • Hepatitis B or C serologic status: subjects who are hepatitis B core antibody (anti-HBc) positive and who are surface antigen negative will need to have a negative polymerase chain reaction (PCR). Those who are hepatitis B surface antigen (HbsAg) positive or hepatitis B PCR positive will be excluded
  • Subjects who are hepatitis C antibody positive will need to have a negative PCR result. Those who are hepatitis C PCR positive will be excluded
  • Known human immunodeficiency virus (HIV) positivity
  • Pregnant or breast feeding

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04257578

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Contact: Ajay Gopal 206-606-2307 agopal@uw.edu

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United States, Washington
Fred Hutch/University of Washington Cancer Consortium Recruiting
Seattle, Washington, United States, 98109
Contact: Ajay Gopal    206-606-2307    agopal@uw.edu   
Principal Investigator: Ajay Gopal         
Sponsors and Collaborators
University of Washington
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Principal Investigator: Ajay Gopal Fred Hutch/University of Washington Cancer Consortium
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Responsible Party: University of Washington
ClinicalTrials.gov Identifier: NCT04257578    
Other Study ID Numbers: RG1006269
NCI-2020-00238 ( Registry Identifier: NCI / CTRP )
10418 ( Other Identifier: Fred Hutch/University of Washington Cancer Consortium )
First Posted: February 6, 2020    Key Record Dates
Last Update Posted: December 13, 2022
Last Verified: December 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by University of Washington:
Non-Hodgkin Lymphoma
Additional relevant MeSH terms:
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Lymphoma, Follicular
Lymphoma, Non-Hodgkin
Lymphoma, B-Cell
Lymphoma, Large B-Cell, Diffuse
Neoplasms by Histologic Type
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Antineoplastic Agents