Pilot Study of Redirected Autologous T Cells Engineered to Contain Monoclonal Antibody (Anti-CD19) Attached to T-cell Receptor Signaling Domain (TCRζ) and Transgene (4-1BB) Signaling Domain in Patients With Chemotherapy Resistant or Refractory CD19+ Leukemia and Lymphoma (Pedi CART-19)
This is a study for children who have been previously treated for Leukemia/Lymphoma. In particular, it is a study for people who have a type of Leukemia/Lymphoma that involves B cells (a type of white cell), which contain the cancer. This is a new approach for treatment of Leukemia/Lymphoma that involves B cells (tumor cells). This study will take the subject's white blood cells (T cells) and modify them in order to target the cancer.
The subject's T cells will be modified in one or two different ways that will allow the cells to identify and kill the tumor cells (B cells). Both ways of modifying the cells tells the T cells to go to the B cells (tumor cells) and turn "on" and potentially kill the B cells (tumor cells). The modification is a genetic change to the T cells, or gene transfer, in order to allow the modified T cells to recognize your tumor cells but not other normal cells in the subject's body. These modified cells are called chimeric antigen receptor 19 (CART19) T-cells.
The two types of CART-19 T cells will be given back to subject's through an infusion. In addition to determining the safety of this approach, the purpose of the study is to determine which way of modifying the T cells works better in turning them "on" to fight cancer. This is done by monitoring levels of both types of modified cells in the subject's blood stream, and if possible, in the bone marrow and tumor tissue for four weeks after the infusion. It is expected that one type of modified cell will grow better than the other in the subject's blood. However, it is possible that there will be no difference between the two types of cells.
All subjects who receive CART19 T cells will be enrolled in a Long Term Follow up study to monitor subjects. Subjects will be followed every 6 months for five years following the 1st infusion of the T cells. If the CART19 T cells are no longer found in the blood after five years, then subjects will be contacted yearly for the next 10 years. If the CART19 T cells are found in the blood at five years after the 1st infusion of T cells, then the subjects will continue to be seen once a year until the CART19 T cells are no longer found in the blood for a maximum of 15 years.
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Pilot Study of Redirected Autologous T Cells Engineered to Contain Anti-CD19 Attached to TCRζ and 4-1BB Signaling Domains in Patients With Chemotherapy Resistant or Refractory CD19+ Leukemia and Lymphoma|
- Number of Participants with Severe/Adverse Events as a Measure of Safety and Tolerability [ Time Frame: 24 weeks ] [ Designated as safety issue: Yes ]Safety of CAR+ T cell infusion and observed side effects
- Ability of two different types of CAR+ T cells to expand and persist in the patient [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]The change in the ratio of the vector transduced cells to each other between baseline and week four will be evaluated. Observation and monitoring of patients will continue on a monthly basis until week 24 post dosing
- Impact of CAR+ T cell infusion on cancer [ Time Frame: 4 weeks ] [ Designated as safety issue: No ]Patients with measurable disease will be assessed for the response of their disease to the CAR+ T cell treatment
|Study Start Date:||August 2011|
|Estimated Study Completion Date:||September 2016|
|Estimated Primary Completion Date:||August 2016 (Final data collection date for primary outcome measure)|
Experimental: CART-19 T Cells
The subject's T cells will be modified in one or two different ways that will allow the cells to identify and kill the tumor cells (B cells).
At entry subjects will be staged and the suitability of their T cells for CART-19 manufacturing will be determined. Subjects who have adequate T cells will be leukapheresed to obtain large numbers of peripheral blood mononuclear cells (PBMC) for CART-19 manufacturing. The T cells will be purified from the PBMC, transduced with CART-19 lentiviral vector, expanded in vitro and then frozen for future administration. Chemotherapy will then be given. Following tumor burden reassessment, CART-19 cells will be thawed and infused.
Subjects will have blood tests to assess safety, and engraftment and persistence of the CART-19 cells at regular intervals through four weeks after their last infusion of the study. The subsets of circulating T-cells that contain the CART-19:T cell receptor (TCR):type 2 transmembrane glycoprotein (4-1BB) and CART-19:TCR only lentiviral vector will be assessed at various times after infusion and compared to the baseline sample. Following the 6 months of intensive follow-up, subjects will be evaluated quarterly for two years with a medical history, a physical examination, and blood tests. Following this evaluation, subjects will enter a roll-over study for annual follow-up by phone and questionnaire for an additional thirteen years to assess for the diagnosis of long-term health problems, such as development of new malignancy.
- Determine the safety and feasibility of administration of chimeric antigen receptor T cells transduced with the anti-CD19 lentiviral vector (referred to as "CART-19" cells).
- Determine duration of in vivo survival of CART-19 cells. Real Time polymerase chain receptor (RT-PCR) analysis of whole blood will be used to detect and quantify survival of CART-19 TCR:4-1BB and TCR cells over time.
- For patients with detectable disease, measure anti-tumor response due to CART-19 cell infusions.
- To determine if the 4-1BB transgene is superior to the TCR only transgene as measured by the relative engraftment levels of CART-19 TCR:4-1BB and TCR cells over time.
- For patients with stored or accessible tumor cells [such as patients with active chronic lymphocytic leukemia (CLL), acute lymphoblastic leukemia (ALL), etc] determine tumor cell killing by CART-19 cells in vitro.
- Determine if cellular or humoral host immunity develops against the murine anti-CD19, and assess correlation with loss of detectable CART-19 (loss of engraftment).
- Determine the relative subsets of CART-19 T cells (Tcm, Tem, and Treg)
|Contact: Stephan A Grupp, MD, PHD||CHOP INFO #: 267-426-0762|
|United States, Pennsylvania|
|CHOP - http://www.chop.edu/service/oncology/pediatric-cancer-research/cart-19-trial.html||Recruiting|
|Philadelphia, Pennsylvania, United States, 19104|
|Contact: Christine Strait, BS email@example.com|
|Contact: Margie Tartaglione, RN firstname.lastname@example.org|
|Principal Investigator: Stephan A Grupp, MD, PHD|