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
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
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:TCR: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.
1. 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).
2. Determine duration of in vivo survival of CART-19 cells. RT-PCR analysis of whole blood
will be used to detect and quantify survival of CART-19 TCR:4-1BB and TCR cells over
1. For patients with detectable disease, measure anti-tumor response due to CART-19 cell
2. 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.
3. For patients with stored or accessible tumor cells (such as patients with active CLL,
ALL, etc) determine tumor cell killing by CART-19 cells in vitro.
4. 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).
5. Determine the relative subsets of CART-19 T cells (Tcm, Tem, and Treg)
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Number of Participants with Severe/Adverse Events as a Measure of Safety and Tolerability
Safety of CAR+ T cell infusion and observed side effects
United States: Food and Drug Administration
|CHOP - http://www.chop.edu/service/oncology/pediatric-cancer-research/cart-19-trial.html||Philadelphia, Pennsylvania 19104|