A Pediatric Trial of Genetically Modified Autologous T Cells Directed Against CD19 for Relapsed CD19+ Acute Lymphoblastic Leukemia
|B Cell Leukemia||Biological: Autologous CD19 CAR+ EGFTt + T cells||Phase 1|
|Study Design:||Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
|Official Title:||Pediatric Leukemia Adoptive Therapy (PLAT)-01: A Phase 1 Feasibility and Safety Study of Cellular Immunotherapy for Relapsed Pediatric CD19+ Acute Lymphoblastic Leukemia Using Autologous T-cells Lentivirally Transduced To Express a CD19-Specific Chimeric Antigen Receptor|
- Number of Participant with Adverse Events [ Time Frame: 42 days ]The safety of the T cell infusion will be described and the maximum tolerated dose determined.
- Persistence of the CD19 CAR+ T cells [ Time Frame: 42 days ]Patients will be followed for 42 days to determine if the transferred T cells remain detectable in the blood and bone marrow
- Determine if there is anti-leukemic activity of the CD19 CAR+ T cells [ Time Frame: 42 days ]Patients will have their bone marrow assessed following the T cell infusion to determine if their disease responded to the treatment
|Study Start Date:||December 2012|
|Estimated Study Completion Date:||January 2031|
|Estimated Primary Completion Date:||January 2031 (Final data collection date for primary outcome measure)|
Experimental: CAR+ T cells
Subjects will receive two days of cyclophosphamide for a total of 3g/m^2 followed several days later by a single dose of Autologous CD19 CAR+ EGFTt + T cells
Biological: Autologous CD19 CAR+ EGFTt + T cells
Autologous T cell modified to express a CD19 specific CAR and a truncated EGFRt tag
Upon meeting the eligibility requirements and enrolling on study, subjects will undergo a blood draw to obtain the T cells for the generation of the CD19 CAR+ T cells. The T cells are isolated from the blood, transduced with a lentivirus to express the CD19 CAR, and expanded in culture over a three week period. During the process of cell generation, subjects will continue to be cared for by their primary oncologist and may undergo additional treatment directed at the leukemia during this time.
After the CAR+ T cells have been generated, the subject undergoes a disease assessment and will be admitted to the hospital to receive 2 days of cyclophosphamide for lymphodepletion and reduction of disease burden. Several days later, the subject will receive an infusion of the CAR+ T cells.
Following treatment with the CAR+ T cells, subjects will be intensely followed for 6 weeks with serial blood testing and re-evaluation of disease status with bone marrow aspirates. After 6 weeks, the subjects clinical care will be resumed by their primary oncologist, and it is possible that they would receive additionally chemotherapy or a stem cell transplant.
Upon completion of the study, subjects will be followed at least annually with a either a medical history, physical exam and blood tests or a phone call/questionnaire for 15 years. This follow up will help to determine if the subject develops any long-term health problems related to the CAR+ T cells including a new cancer.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01683279
|United States, Washington|
|Seattle Children's Hospital|
|Seattle, Washington, United States, 98105|
|Principal Investigator:||Rebecca Gardner, MD||Seattle Children's Hospital|