Clinical Trials /

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

NCT04257578

Description:

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.

Related Conditions:
  • Diffuse Large B-Cell Lymphoma, Not Otherwise Specified
  • High Grade B-Cell Lymphoma, Not Otherwise Specified
  • Primary Mediastinal B-Cell Lymphoma
  • Transformed Lymphoma
Recruiting Status:

Not yet recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Acalabrutinib and Anti-CD19 CAR T-cell Therapy for the Treatment of B-cell Lymphoma
  • Official Title: Acalabrutinib in Combination With Anti-CD19 Chimeric Antigen Receptor T-Cells (CART) in B-Cell Lymphoma

Clinical Trial IDs

  • ORG STUDY ID: RG1006269
  • SECONDARY ID: NCI-2020-00238
  • SECONDARY ID: P30CA015704
  • NCT ID: NCT04257578

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

Interventions

DrugSynonymsArms
Acalabrutinib1420477-60-6, ACP-196, Bruton Tyrosine Kinase Inhibitor ACP-196, CalquenceTreatment (acalabrutinib, axicabtagene ciloleucel)
Axicabtagene CiloleucelKTE C19, KTE-C19, KTE-C19 CAR, YescartaTreatment (acalabrutinib, axicabtagene ciloleucel)

Purpose

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.

Detailed Description

      OUTLINE:

      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.
    

Trial Arms

NameTypeDescriptionInterventions
Treatment (acalabrutinib, axicabtagene ciloleucel)ExperimentalBeginning 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.
  • Acalabrutinib
  • Axicabtagene Ciloleucel

Eligibility Criteria

        Inclusion Criteria:

          -  Histologically confirmed large B-cell lymphoma after two or more lines of systemic
             therapy, 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

          -  Criteria must be met for receiving commercial axi-cel per Food and Drug Administration
             (FDA) label

          -  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

          -  Evidence of CD19 expression on tumor cells by immunohistochemistry or flow cytometry

          -  Creatinine clearance (CrCl) > 50 mL/min or serum creatinine =< 2.5

          -  Total bilirubin =< 1.5 x the upper limit of normal

          -  Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 3 x the upper
             limit of normal

          -  Adequate pulmonary function, defined as =< grade 1 dyspnea and oxygen saturation
             (SaO2) >= 92% on room air

          -  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)

        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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Incidence of adverse events
Time Frame:Up to 30 days post axicabtagene ciloleucel infusion
Safety Issue:
Description: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

Measure:Complete response rate following chimeric antigen receptor T-cells therapy (CART)
Time Frame:Up to 5 years post treatment
Safety Issue:
Description:Will be assessed per Lugano criteria.
Measure:Overall survival
Time Frame:Up to 5 years post treatment
Safety Issue:
Description:
Measure:Progression-free survival
Time Frame:Up to 5 years post treatment
Safety Issue:
Description:
Measure:Response rate
Time Frame:Up to 3 weeks
Safety Issue:
Description:Will assess response rate (complete response + partial response + stable response) following bridging prior to CART.

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:University of Washington

Trial Keywords

  • Non-Hodgkin's Lymphoma

Last Updated

February 3, 2020