Trial Information

Administration of Tumor-Associated Antigen (TAA)-Specific Cytotoxic T-Lymphocytes to Patients With Active or Relapsed Hodgkin or Non-Hodgkin Lymphoma

OBJECTIVES:

- To determine the safety of 2 intravenous injections of autologous tumor-associated
antigen (TAA)-specific cytotoxic T-lymphocytes (CTL) in patients with Hodgkin (HL) or
non-Hodgkin lymphoma (NHL).

- To determine whether infusion of TAA-specific T cells targeting multiple tumor antigens
has a safety profile similar to the adoptive transfer of single antigen-targeted T
cells.

- To obtain information on the expansion, persistence, and anti-tumor effects of the
adoptively transferred TAA-specific CTL in patients with HL or NHL.

- To determine whether CTL infusions increase the spectrum of epitopes/antigens targeted
by endogenous T cells (epitope spreading).

OUTLINE: This is a multicenter, dose-escalation study. Patients are stratified according to
cytotoxic T-lymphocytes (CTLs) treatment (as therapy for HL or NHL [Group A] vs adjunctive
therapy following autologous or syngeneic transplantation [Group B]).

Patients undergo peripheral blood mononuclear cells collection for cytoxic T-cell
lymphocytes (CTLs) generation. T cells are stimulated with antigen-presenting cells,
dendritic cells (DC) pulsed with pepmixes spanning the tumor-associated antigens SSX2,
MAGEA4, Survivin, PRAME, and NY-ESO-1 in the presence of pro-proliferative cytokines
interleukin (IL)-7, IL-12, IL-15, and IL-6 . Cells are then expanded in the presence of
IL-2.

Antigen-escalation stage: Patients receive autologous tumor-associated antigen
(TAA)-specific CTLs IV over 10 minutes on days 0 (PRAME- and SSX-specific T cells) and 28
(PRAME/SSX/MAGE/NY-ESO-specific T cells) in the absence of disease progression or
unacceptable toxicity.

Dose-escalation stage: Patients receive autologous TAA-specific CTLs IV over 10 minutes on
days 0 (PRAME- and SSX-specific T cells) and 14 (PRAME/SSX/MAGE/NY-ESO-specific T cells).
Patients with stable disease or responsive disease (partial response) receive up to 3
courses (6 doses) every 6 weeks in the absence of disease progression or unacceptable
toxicity.

After completion of treatment, patients are followed up every 2 weeks for 8 weeks and then
at 3, 6, 9, and 12 months.