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Clinical trial information and results are updated daily from ClinicalTrials.gov. The latest data update was conducted on 01/23/2021.
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Drug Interventions

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Clinical trial information and results are updated daily from ClinicalTrials.gov. The latest data update was conducted on 01/23/2021.

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)

Clinicaltrials.gov identifier NCT03938987

Recruitment Status Not yet recruiting

First Posted May 6, 2019

Last update posted June 4, 2020

Study Description

Brief 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).

  • Condition or Disease:Relapsed Non Hodgkin Lymphoma
    Relapsed Adult ALL
    Relapsed Pediatric ALL
  • Intervention/Treatment: Biological: autologous CD19-directed chimeric antigen receptor (CAR) T-cells
  • Phase: Phase 1/Phase 2
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.

Study Design
  • Study Type: Interventional
  • Estimated Enrollment: 63 participants
  • Intervention Model: Single Group Assignment
  • Intervention Model Description: All enrolled patients will be included in the safety and PK analyses. All patients receiving the dose and schedule selected for expansion will be included in the efficacy and futility analyses including patients who received the selected dose and schedule in the phase 1b dose selection and dose escalation. Analysis of during phase 2 will occur using a Simon 2-stage design.
  • Masking: None (Open Label) ()
  • Primary Purpose: Treatment
  • 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)
  • Estimated Study Start Date: September 2020
  • Estimated Primary Completion Date: December 2022
  • Estimated Study Completion Date: December 2024
Arms and interventions
Arm Intervention/treatment
Experimental: CAR T cells
Patients with relapsed/refractory B-cell ALL or NHL.
Biological: autologous CD19-directed chimeric antigen receptor (CAR) T-cells
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/m2/day) on Days -5, -4, and -3 prior to a CAR T-cell intravenous, single dose administration on Day 0.
Outcome Measures
  • Primary Outcome Measures: 1. Number and type of treatment-related adverse events. [ Time Frame: 3 years ]
  • 2. Number of dose limiting toxicities of anti-CD19 CAR T-cells [ Time Frame: 3 years ]
  • 3. Maximum concentration (Cmax). [ Time Frame: 3 years ]
  • 4. Time to maximum concentration (Tmax). [ Time Frame: 3 years ]
  • 5. Area-Under-the-Concentration-vs-time curve (AUC) in peripheral blood and/or bone marrow. [ Time Frame: 3 years ]
  • 6. Overall objective response rate (ORR: proportion of patients with confirmed responses of complete [CR] or partial [PR]) [ Time Frame: 3 years ]
Eligibility Criteria
  • Ages Eligible for Study: 2 to 70 Years (Child, Adult, Older Adult)
  • Sexes Eligible for Study: All
  • Accepts Healthy Volunteers: No
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 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.

Contacts and Locations
Contacts

Contact: Zack Breckenridge 7803917687 zackariah.breckenridge@ahs.ca

Locations

Canada, Alberta
Foothills Medical Centre
Calgary

Canada, Alberta
Tom Baker Cancer Centre
Calgary

Canada, Alberta
Alberta Children's Hospital
Calgary

Canada, Alberta
Cross Cancer Institute
Edmonton

Canada, Alberta
Stollery Children's Hospital
Edmonton

Canada, Alberta
University of Alberta Hospital
Edmonton

Sponsors and Collaborators

University of Alberta

Alberta Cancer Foundation

Canadian Cancer Trials Group

Investigators

Principal Investigator: Dr. Michael P Chu, MD Cross Cancer Institute

More Information
  • Responsible Party: University of Alberta
  • ClinicalTrials.gov Identifier: NCT03938987 History of Changes
  • Other Study ID Numbers: ACIT001/EXC002
  • First Posted: May 6, 2019 Key Record Dates
  • Last Update Posted: June 4, 2020
  • Last Verified: June 2020
  • Individual Participant
    Data (IPD) Sharing
    Statement:
  • Plan to Share IPD: No
  • Studies a U.S. FDA-regulated Drug Product: No
  • Studies a U.S. FDA-regulated Device Product: No
  • Additional relevant MeSH terms: Lymphoma
    Precursor Cell Lymphoblastic Leukemia-Lymphoma
    Leukemia, Lymphoid