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T-cells Expressing Anti-CD19 CAR in Pediatric and Young Adults With B-cell Malignancies

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ClinicalTrials.gov Identifier: NCT02772198
Recruitment Status : Unknown
Verified April 2018 by Sheba Medical Center.
Recruitment status was:  Recruiting
First Posted : May 13, 2016
Last Update Posted : April 27, 2018
Sponsor:
Information provided by (Responsible Party):
Sheba Medical Center

Tracking Information
First Submitted Date  ICMJE May 9, 2016
First Posted Date  ICMJE May 13, 2016
Last Update Posted Date April 27, 2018
Study Start Date  ICMJE November 2016
Estimated Primary Completion Date July 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: November 2, 2016)
  • Number of patients with treatment related adverse events as assessed by CTCAE v4. [ Time Frame: 2 years ]
  • Overall Response Rate [ Time Frame: 28 days ]
    Overall response rate = complete response (CR) + partial response (PR) + complete response with incomplete count recovery (CRi) in leukemia patients; Assessment using bone marrow evaluation for patients with leukemia, and imaging (CT / PET CT) for patients with lymphoma
  • Feasibility of CD19 CAR T cell production as defined by number of products successfully meeting release criteria [ Time Frame: 12 days ]
    For each participant, the feasibility of generating sufficient autologous CAR T cells within 12 days will be evaluated.
Original Primary Outcome Measures  ICMJE
 (submitted: May 12, 2016)
  • Number of patients with treatment related adverse events as assessed by CTCAE v4. [ Time Frame: 2 years ]
  • Overall Response Rate [ Time Frame: 28 days ]
    Overall response rate = complete response (CR) + partial response (PR) + complete response with incomplete count recoveri (CRi) in leukemia patients; Assessment using bone marrow evaluation for patients with leukemia, and imaging (CT / PET CT) for patients with lymphoma
  • Feasibility of CD19 CAR T cell production as defined by number of products successfully meeting release criteria [ Time Frame: 12 days ]
    For each participant, the feasibility of generating sufficient autologous CAR T cells within 12 days will be evaluated.
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: November 2, 2016)
  • CAR T cell persistence as measured by enumeration of CAR T cells in the blood and bone marrow of participants [ Time Frame: 1 year ]
    Enumeration of CAR T cells in the blood and bone marrow of participants
  • T cell activity and exhaustion profile as measured by flow cytometry [ Time Frame: 3 months ]
    Assessment of T cells from peripheral blood by flow cytometry for expression of activation and exhaustion markers.
  • Cytokine levels in the peripheral blood of the patients [ Time Frame: 30 days ]
    Measurement of cytokines in the blood of participants following CAR T cell administration
Original Secondary Outcome Measures  ICMJE
 (submitted: May 12, 2016)
  • CAR T cell persistence as measured by enumeration of CAR T cells in the blood and bone marrow of participants [ Time Frame: 1 year ]
    Enumeration of CAR T cells in the blood and bone marrow of participants
  • T cell activity and exhaustion profile as measured by flow cytometry [ Time Frame: 3 months ]
    Assessment of T cells from peripheral blood by flow cytometry for expression of activation and exhasution markers.
  • Cytokine levels in the peripheral blood of the patients [ Time Frame: 30 days ]
    Measurement of cytokines in the blood of participants following CAR T cell administration
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE T-cells Expressing Anti-CD19 CAR in Pediatric and Young Adults With B-cell Malignancies
Official Title  ICMJE A Phase 1 / 2 Single Arm Study of T-cells Expressing Anti-CD19 Chimeric Antigen Receptor in Pediatric and Young Adult Patients With B-cell Malignancies
Brief Summary This phase 1 / 2 study will evaluate the response of B-cell malignancies expressing CD19 to autologous T cells transduced with a second generation anti-CD19 chimeric antigen receptor in children and young adults.
Detailed Description

Autologous T cells transduced with chimeric antigen receptors (CAR) that recognize the CD19 antigen (CD19-CAR T cells) have been used in multiple clinical trials at several institutions worldwide. We established an in-house manufacturing process for CD19-CAR T cells with a CD28 (cluster of differentiation 28) costimulatory domain.

Primary Objectives:

  1. To study the safety of administration of CAR T cell at the Sheba Medical Center
  2. To determine the feasibility and efficacy of administering anti-CD19-CAR T cells in children and young adults with B cell malignancies.

Secondary Objectives

  1. To study in vivo and in vitro behavior of CAR T cell in patients, including persistence, expansion, cytotoxic potential and exhaustion.
  2. To study the cytokine milieu in CAR treated patients.

Eligibility Patients 1-50 years of age, with a CD19-expressing B-cell malignancy that has recurred after, or not responded to, one or more standard chemotherapy-containing regimens.

Design Peripheral blood mononuclear cells (PBMCs)will be obtained by leukapheresis. Anti-CD19 CAR T cells will be manufactured from fresh autologous PBMCs. PBMC will be cultured in the presence of anti-CD3 (cluster of differentiation 3) antibody and interleukin-2 followed by retroviral vector supernatant containing the anti-CD19 CAR. Total culture time is between 7-10 days. Patients will receive lymphodepleting chemotherapy composed of cyclophosphamide and fludarabine prior to cell infusion, and on day 0 will receive one million CAR T cells per kilogram. Patients will be monitored for toxicity including cytokine release syndrome, hematologic toxicities and B-cell aplasia; for response of their underlying malignancy; and for CAR-T cell persistence in the blood, marrow and cerebral spinal fluid (CSF).

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Acute Lymphoblastic Leukemia, B-precursor
  • Non-Hodgkin Lymphoma, B-cell
Intervention  ICMJE Biological: CD19 CAR T cells
Autologous T cells activated and transduced with a chimeric antigen receptor targeting CD19
Study Arms  ICMJE Experimental: Single Arm
All patients will be treated on this single arm
Intervention: Biological: CD19 CAR T cells
Publications * Itzhaki O, Jacoby E, Nissani A, Levi M, Nagler A, Kubi A, Brezinger K, Brayer H, Zeltzer LA, Rozenbaum M, Vernitsky H, Markel G, Toren A, Avigdor A, Schachter J, Besser MJ. Head-to-head comparison of in-house produced CD19 CAR-T cell in ALL and NHL patients. J Immunother Cancer. 2020 Mar;8(1). pii: e000148. doi: 10.1136/jitc-2019-000148.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Unknown status
Estimated Enrollment  ICMJE
 (submitted: April 25, 2018)
80
Original Estimated Enrollment  ICMJE
 (submitted: May 12, 2016)
40
Estimated Study Completion Date  ICMJE November 2019
Estimated Primary Completion Date July 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Patient with relapsed or refractory B-cell malignancy
  • Age 1-50 years
  • CD19 expression shown by flow cytometry or immunohistochemistry on at least 70% of leukemic blasts / lymphoma cells
  • Adequate CD3 count (above 250 CD3+ cells per microliter blood)
  • Clinical performance status: Patients > 10 years of age: Karnofsky ≥ 50%; Patients ≤ 10 years of age: Lansky scale ≥ 50%. Exception for neurologic symptoms (e.g. paralysis) that are explained by the malignancy.
  • Females of child-bearing potential must have a negative pregnancy test
  • Cardiac function: Left ventricular ejection fraction >45% or shortening fraction >28%
  • For patients following allogeneic bone marrow transplantation - at least 100 days post BMT with no signs or symptoms of active graft-versus-host disease.

Key Exclusion Criteria:

  • Hyperleukocytosis (WBC>50,000) or rapidly progressive disease
  • Pregnant or breast-feeding females
  • Hepatic dysfunction, defined as bilirubin > x2 upper normal limit (except when explained by hemolysis or Gilbert) or serum glutamate oxaloacetate transaminase > x25 upper normal limit.
  • Hepatitis B, Hepatitis C or HIV infection.
  • Anti-neoplastic treatment given in the 2 weeks prior to apheresis, with the exception of intrathecal chemotherapy.
  • Active immunosuppressive therapy
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 1 Year to 50 Years   (Child, Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Israel
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02772198
Other Study ID Numbers  ICMJE SHEBA-15-2076-AT-CTIL
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: Undecided
Responsible Party Sheba Medical Center
Study Sponsor  ICMJE Sheba Medical Center
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account Sheba Medical Center
Verification Date April 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP