A Phase I/IIa Trial For The Treatment of Relapsed or Chemotherapy Refractory Chronic Lymphocytic Leukemia or Indolent B Cell Lymphoma Using Autologous T Cells Genetically Targeted to the B Cell Specific Antigen CD19
Phase 1: The primary objective is to assess the safety of autologous T cells genetically
modified to express chimeric antigen receptor (CAR) targeting CD19 antigen (19-28z) with or
without conditioning chemotherapy.
• Phase IIa: The primary objective is to compare the relative engraftment and persistence of
the two CAR modified CD19-targeted T cells expressing different co-stimulatory signaling
domain CD28 (19-28z) and 4-1BB (CART-19:CD3z-4-1BB) in the CAR construct.
To compare the in vivo survival of genetically modified 19-28z CAR+ T cells after T cell
infusion alone or in combination with conditioning chemotherapy.
- To compare the gene transfer/expression efficiency of the two viral vectors (retrovirus
- To assess the anti-leukemic activity of adoptively transferred CD19-targeted modified T
cells linked to the CD28 (19-28z) and 4-1BB signaling domains (CART-19:CD3z-4-1BB).
The first stage is a standard 3-step phase I dose escalation trial to assess the safety of
19-28z CAR expressing autologous T cells with or without prior conditioning chemotherapy. In
Step 1, a cohort of patients will receive the lowest planned dose of 19-28z+ modified T
cells. In Step 2, a cohort of patients will receive cyclophosphamide conditioning
chemotherapy followed by the lowest planned dose of 19-28z+ modified T cells. In Step 3, a
cohort of patients will be treated with the investigator's choice conditioning chemotherapy
followed by the higher dose of 19-28z+ modified T cells. In all cohorts, 3-6 patients will
be treated at each dose level, and dose escalation will proceed (from step 3 to step 3) if
less than 33% of patients in a cohort experience unanticipated dose-limiting toxicity.
In the Phase IIa extension part of the trial, 6 patients from MSKCC will be enrolled, and
will be treated with co-infusion of 19-28z and CART-19:CD3z-4-1BB+ modified T cells mixed at
1:1 ratio at the MTD of T cells determined from the phase I trial.
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Safety (phase I)
Renier Brentjens, MD, PhD
Memorial Sloan-Kettering Cancer Center
United States: Food and Drug Administration
|Memorial Sloan-Kettering Cancer Center||New York, New York 10021|