Clinical Study of Chimeric CD(Cluster of Differentiation)33 Antigen Receptor-modified T Cells in Relapsed and/or Chemotherapy Refractory Acute Myeloid Leukemias
I. Determine the safety and feasibility of the chimeric antigen receptor T cells transduced
with the anti-CD33 vector (referred to as CART-33 cells).
II. Determine duration of in vivo survival of CART-33 cells. RT-PCR (reverse transcription
polymerase chain reaction) analysis of whole blood will be used to detect and quantify
survival of CART-33 TCR zeta:CD137 and TCR (T-cell receptor) zeta cells over time.
I. For patients with detectable disease, measure anti-leukemia response due to CART-33 cell
II. To determine if the CD137 transgene is superior to the TCR zeta only transgene as
measured by the relative engraftment levels of CART-33 TCR zeta:CD137 and TCR zeta cells
III. Estimate relative trafficking of CART-33 cells in bone marrow.
IV. For patients with stored or accessible leukemia blasts, determine leukemia cell killing
by CART-33 cells in vitro.
V. Determine if cellular or humoral host immunity develops against the murine anti-CD33, and
assess correlation with loss of detectable CART-33 (loss of engraftment).
VI. Determine the relative subsets of CART-33 T cells (Tcm, Tem, and Treg).
OUTLINE: Patients are assigned to 1 group according to order of enrollment.
Patients receive anti-CD33-CAR (coupled with CD137 and CD3 zeta signalling
domains)vector-transduced autologous T cells on days 0,1, and 2 in the absence of disease
progression or unacceptable toxicity.
After completion of study treatment, patients are followed intensively for 6 months, every 3
months for 2 years, and annually thereafter for 13 years.
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Occurrence of study related adverse events
defined as >= Grade 3 signs/symptoms, laboratory toxicities, and clinical events) that are possibly, likely, or definitely related to study treatment
Until week 24
China: Ethics Committee