T-cells Expressing Anti-CD19 CAR in Pediatric and Young Adults With B-cell Malignancies
|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: NCT02772198|
Recruitment Status : Recruiting
First Posted : May 13, 2016
Last Update Posted : November 3, 2020
|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|
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.
- To study the safety of administration of CAR T cell at the Sheba Medical Center
- To determine the feasibility and efficacy of administering anti-CD19-CAR T cells in children and young adults with B cell malignancies.
- To study in vivo and in vitro behavior of CAR T cell in patients, including persistence, expansion, cytotoxic potential and exhaustion.
- 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 :||Interventional|
|Estimated Enrollment :||300 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|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|
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
- 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.
- 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
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
|Contact: Amos Toren, MD,Phdemail@example.com|
|Contact: Elad Jacoby, MDfirstname.lastname@example.org|