Working…
COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
ClinicalTrials.gov
ClinicalTrials.gov Menu

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)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03938987
Recruitment Status : Not yet recruiting
First Posted : May 6, 2019
Last Update Posted : May 6, 2019
Sponsor:
Collaborators:
Alberta Cancer Foundation
Canadian Cancer Trials Group
Information provided by (Responsible Party):
University of Alberta

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 Intervention/treatment Phase
Relapsed Non Hodgkin Lymphoma Relapsed Adult ALL Relapsed Pediatric ALL Biological: autologous CD19-directed chimeric antigen receptor (CAR) T-cells 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.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
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 : July 2019
Estimated Primary Completion Date : December 2022
Estimated Study Completion Date : December 2024


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.




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 ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   2 Years 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 < 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.

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): NCT03938987


Contacts
Layout table for location contacts
Contact: Zack Breckenridge 7803917687 zackariah.breckenridge@ahs.ca

Locations
Layout table for location information
Canada, Alberta
Foothills Medical Centre
Calgary, Alberta, Canada, T2N2T9
Contact: Dr. Andrew Daly, MD         
Tom Baker Cancer Centre
Calgary, Alberta, Canada, T2N4N2
Contact: Dr. Peter Duggan, MD         
Alberta Children's Hospital
Calgary, Alberta, Canada, T3B6A8
Contact: Dr. Victor Lewis, MD         
Cross Cancer Institute
Edmonton, Alberta, Canada, T6G1Z2
Contact: Dr. Michael P Chu, MD         
Stollery Children's Hospital
Edmonton, Alberta, Canada, T6G2B7
Contact: Dr. Sunil Desai, MD         
University of Alberta Hospital
Edmonton, Alberta, Canada, T6G2B7
Contact: Dr. Tiffany Van Slyke, MD         
Sponsors and Collaborators
University of Alberta
Alberta Cancer Foundation
Canadian Cancer Trials Group
Investigators
Layout table for investigator information
Principal Investigator: Dr. Michael P Chu, MD Cross Cancer Institute

Layout table for additonal information
Responsible Party: University of Alberta
ClinicalTrials.gov Identifier: NCT03938987    
Other Study ID Numbers: ACIT001/EXC002
First Posted: May 6, 2019    Key Record Dates
Last Update Posted: May 6, 2019
Last Verified: April 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
Layout table for MeSH terms
Lymphoma
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Leukemia, Lymphoid
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Leukemia