Clinical Trials /

Anti-CD19, Dual Co-stimulatory (4-1BB, CD3ζ) Chimeric Antigen Receptor T-cells in Patients With Relapsed/Refractory Aggressive Lymphoma or Acute Lymphoblastic Leukemia (ALL)

NCT03938987

Description:

Autologous, unselected CD3+ lymphocytes collected from apheresis, transfected with a lentiviral vector containing a 2nd generation chimeric antigen receptor (CAR) consisting of a scFv recognizing CD19 and dual co-stimulatory intracellular signaling domains (4-1BB and CD3ζ).

Related Conditions:
  • Acute Lymphoblastic Leukemia
  • Non-Hodgkin Lymphoma
Recruiting Status:

Not yet recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Anti-CD19, Dual Co-stimulatory (4-1BB, CD3ζ) Chimeric Antigen Receptor T-cells in Patients With Relapsed/Refractory Aggressive Lymphoma or Acute Lymphoblastic Leukemia (ALL)
  • Official Title: A Phase 1b/2 Multi-center, De-centralized, Dose Selection Study of Autologous CD19-directed Chimeric Antigen Receptor (CAR) T-cells in Patients With Relapsed/Refractory Aggressive Lymphoma or Acute Lymphoblastic Leukemia (ALL)

Clinical Trial IDs

  • ORG STUDY ID: ACIT001/EXC002
  • NCT ID: NCT03938987

Conditions

  • Relapsed Non Hodgkin Lymphoma
  • Relapsed Adult ALL
  • Relapsed Pediatric ALL

Interventions

DrugSynonymsArms
autologous CD19-directed chimeric antigen receptor (CAR) T-cellsCAR T cells

Purpose

Autologous, unselected CD3+ lymphocytes collected from apheresis, transfected with a lentiviral vector containing a 2nd generation chimeric antigen receptor (CAR) consisting of a scFv recognizing CD19 and dual co-stimulatory intracellular signaling domains (4-1BB and CD3ζ).

Detailed Description

      Anti-CD19/4-1BB/CD3ζ CAR T-cell: autologous, unselected CD3+ lymphocytes collected from whole
      blood or apheresis, transfected with a lentiviral vector containing a 2nd generation chimeric
      antigen receptor (CAR) consisting of a scFv recognizing CD19 and dual co-stimulatory
      intracellular signaling domains (4-1BB and CD3ζ). All patients will receive lymphodepleting,
      conditioning chemotherapy in the form of cyclophosphamide (500 mg/m2/day) and fludarabine (30
      mg/m^2/day) on Days -5, -4, and -3 prior to a CAR T-cell intravenous, single dose
      administration on Day 0.

      Phase 1b: Dose Finding/Escalation Dose Level 1: 0.5 x 10^6/kg Dose Level 2: 1.0 x 10^6/kg
      Dose Level 3: 2.0 x 10^6/kg

      Phase 2: Expansion Patients will receive lymphodepleting chemotherapy as indicated prior to
      receiving the CAR T-cell intravenous, single dose administration on Day 0 at the RP2D as
      identified during Phase 1b.
    

Trial Arms

NameTypeDescriptionInterventions
CAR T cellsExperimentalPatients with relapsed/refractory B-cell ALL or NHL.
  • autologous CD19-directed chimeric antigen receptor (CAR) T-cells

Eligibility Criteria

        Inclusion Criteria:

          1. Have given written informed consent prior to any study-specific procedures; children
             (defined as 17 years of age or less) require guardian consent.

          2. Eastern Cooperative Oncology Group (ECOG) Performance Status 0-2; or Karnofsky > 50%.

          3. Age of 2 to 70 years at time of screening.

          4. A histologically or cytologically documented, CD19+ non-hodgkin's lymphoma or ALL.

          5. At least 1 measurable lesion or FDG-avid disease by positron-emission
             tomography/computed tomography (PET/CT) for lymphoma patients; quantifiable evidence
             of ALL in either peripheral blood or bone marrow aspirate.

          6. Tumor tissue (archival or recent acquisition) must be available for correlative
             laboratory studies (such as immunohistochemistry, and others).

          7. At least 2 prior systemic therapies and patient must not be eligible for potentially
             curative standard-of-care therapy.

          8. Adequate renal function (defined as Cockroft-Gault creatinine clearance > 50 mL/min)
             and hepatic function (total bilirubin < 1.5x ULN; and AST/ALT < 3x ULN) unless
             directly related to malignant disease being treated for on study as demonstrated
             either by PET/CT imaging or by biopsy and histopathologic confirmation.

          9. For women of childbearing potential: agreement to remain abstinent (refrain from
             heterosexual intercourse) or use contraceptive methods that result in a failure rate
             of < 1% per year during the treatment period and for at least 90 days after the last
             dose of study treatment. A woman is considered to be of childbearing potential if she
             is postmenarcheal, has not reached a postmenopausal state (≥ 12 continuous months of
             amenorrhea with no identified cause other than menopause), and has not undergone
             surgical sterilization (removal of ovaries and/or uterus). Examples of contraceptive
             methods with a failure rate of < 1% per year include bilateral tubal ligation, male
             sterilization, established proper use of hormonal contraceptives that inhibit
             ovulation, hormone-releasing intrauterine devices, and copper intrauterine devices.
             The reliability of sexual abstinence should be evaluated in relation to the duration
             of the clinical trial and the preferred and usual lifestyle of the patient. Periodic
             abstinence (e.g., calendar, ovulation, symptothermal, or postovulation methods) and
             withdrawal are not acceptable methods of contraception.

         10. Male participants should agree to not donate sperm during study period (i.e. up to 2
             years following CAR T-cell administration).

         11. Male participants with reproductive potential must agree to use medical approved
             contraceptives during the study and for 90 days following the last dose of study
             treatment.

         12. Are reliable and willing to make themselves available for the duration of the study,
             and are willing to follow study procedures.

        Exclusion Criteria:

          1. Prior treatment with immunotherapy directly targeting T-cells (except anti-thymocyte
             globulin [ATG]), CD19-directed antibody-based therapies (except blinatumomab), or
             other gene therapy products.

          2. Received any investigational drug/anti-cancer therapy within 30 days.

          3. Concurrent participation in another therapeutic clinical trial.

          4. Therapeutic doses of corticosteroids (defined as > 20 mg/day prednisone or equivalent)
             within 7 days prior to blood collection for CAR T-cell product manufacture.

          5. Donor lymphocyte infusion (DLI) within 4 weeks prior to leukapheresis.

          6. Salvage or debulking chemotherapy within 1 week prior to blood collection for CAR
             T-cell product manufacture.

          7. Prior central nervous system (CNS) involvement.

          8. Unresolved acute toxicity of National Cancer Institute Common Terminology Criteria for
             Adverse Events (NCI CTCAE) v4.03 Grade >1 (or baseline, whichever is greater) from
             prior anticancer therapy. Alopecia and other nonacute toxicities are acceptable.

          9. An uncontrolled intercurrent illness including but not limited to ongoing or active
             infection (including fever within 48 hours of screening), symptomatic congestive heart
             failure (i.e., New York Heart Association [NYHA] Class 3 or 4), unstable angina
             pectoris, clinically significant and uncontrolled cardiac arrhythmia, or psychiatric
             illness/social situations that would limit compliance with study requirements.

         10. Major surgical procedure within 30 days.

         11. Known history of human immunodeficiency virus (HIV) or active infection requiring
             therapy, or positive tests for hepatitis B surface antigen or hepatitis C ribonucleic
             acid (RNA).

         12. Any vaccination against infectious diseases (e.g., influenza, varicella) within 4
             weeks (28 days) of initiation of study treatment.

         13. A woman who is pregnant or breastfeeding.
      
Maximum Eligible Age:70 Years
Minimum Eligible Age:2 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Number and type of treatment-related adverse events.
Time Frame:3 years
Safety Issue:
Description:

Details

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

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