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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 October 2020 by Sheba Medical Center.
Recruitment status was:  Recruiting
First Posted : May 13, 2016
Last Update Posted : November 3, 2020
Information provided by (Responsible Party):
Sheba Medical Center

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.

Condition or disease Intervention/treatment Phase
Acute Lymphoblastic Leukemia, B-precursor Non-Hodgkin Lymphoma, B-cell Biological: CD19 CAR T cells Phase 1 Phase 2

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).

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 300 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: 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
Actual Study Start Date : November 2016
Estimated Primary Completion Date : July 2022
Estimated Study Completion Date : November 2022

Arm Intervention/treatment
Experimental: Single Arm
All patients will be treated on this single arm
Biological: CD19 CAR T cells
Autologous T cells activated and transduced with a chimeric antigen receptor targeting CD19

Primary Outcome Measures :
  1. Number of patients with treatment related adverse events as assessed by CTCAE v4. [ Time Frame: 2 years ]
  2. 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

  3. 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.

Secondary Outcome Measures :
  1. 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

  2. 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.

  3. 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

Information from the National Library of Medicine

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Ages Eligible for Study:   1 Year to 50 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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

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): NCT02772198

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Contact: Amos Toren, MD,Phd 03-5302934 amos.toren@sheba.health.gov.il
Contact: Elad Jacoby, MD 03-5302934 elad.jacoby@sheba.health.gov.il

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Chaim Sheba Medical Center Recruiting
Ramat Gan, Israel
Contact: Diana Bar    +972-3-5303699    Diana.Chigalayev@sheba.health.gov.il   
Contact: Elad Jacoby, MD    +972-3-5302934    elad.jacoby@sheba.health.gov.il   
Sponsors and Collaborators
Sheba Medical Center
Publications of Results:
Other Publications:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Sheba Medical Center
ClinicalTrials.gov Identifier: NCT02772198    
Other Study ID Numbers: SHEBA-15-2076-AT-CTIL
First Posted: May 13, 2016    Key Record Dates
Last Update Posted: November 3, 2020
Last Verified: October 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided
Additional relevant MeSH terms:
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Precursor Cell Lymphoblastic Leukemia-Lymphoma
Lymphoma, B-Cell
Lymphoma, Non-Hodgkin
Neoplasms by Histologic Type
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Leukemia, Lymphoid