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) (ACIT001/EXC002)

  • STATUS
    Recruiting
  • End date
    Dec 21, 2024
  • participants needed
    63
  • sponsor
    University of Alberta
Updated on 4 October 2022

Summary

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).

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.

Details
Condition Relapsed Non Hodgkin Lymphoma, Relapsed Adult ALL, Relapsed Pediatric ALL
Treatment autologous CD19-directed chimeric antigen receptor (CAR) T-cells
Clinical Study IdentifierNCT03938987
SponsorUniversity of Alberta
Last Modified on4 October 2022

Eligibility

Yes No Not Sure

Inclusion Criteria

Have given written informed consent prior to any study-specific procedures; children (defined as 17 years of age or less) require guardian consent
Eastern Cooperative Oncology Group (ECOG) Performance Status 0-2; or Karnofsky > 50%
Age of 2 to 70 years at time of screening
A histologically or cytologically documented, CD19+ non-hodgkin's lymphoma or ALL
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
Tumor tissue (archival or recent acquisition) must be available for correlative laboratory studies (such as immunohistochemistry, and others)
At least 2 prior systemic therapies and patient must not be eligible for potentially curative standard-of-care therapy
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
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
Male participants should agree to not donate sperm during study period (i.e. up to 2 years following CAR T-cell administration)
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
Are reliable and willing to make themselves available for the duration of the study, and are willing to follow study procedures

Exclusion Criteria

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
Received any investigational drug/anti-cancer therapy within 30 days
Concurrent participation in another therapeutic clinical trial
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
Donor lymphocyte infusion (DLI) within 4 weeks prior to leukapheresis
Salvage or debulking chemotherapy within 1 week prior to blood collection for CAR T-cell product manufacture
Prior central nervous system (CNS) involvement
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
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
Major surgical procedure within 30 days
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)
Any vaccination against infectious diseases (e.g., influenza, varicella) within 4 weeks (28 days) of initiation of study treatment
A woman who is pregnant or breastfeeding
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