Trial Information

Adoptive Cell Therapy for B-Cell Malignancies After Allogeneic Hematopoietic Stem Cell Transplantation With Costimulated, Tumor-Derived Lymphocytes

OBJECTIVES:

Primary

- Determine the feasibility of administering ex vivo costimulated, expanded, clinically
relevant numbers of tumor-derived lymphocytes (TDL) from surgically resected tumor
(TDL) and tumor-involved bone marrow (marrow-TDL) in patients with persistent or
recurrent B-cell lymphoid malignancies after prior allogeneic hematopoietic stem cell
transplantation (alloHSCT).

- Determine the safety of TDL, in terms of the incidence of infusion-related toxicities,
hyperacute graft-versus-host disease (GVHD), or acute or chronic GVHD, in these
patients.

Secondary

- Determine antitumor response in patients treated with TDL.

- Investigate methods of characterizing residual tumor after alloHSCT by evaluating
patient tumor and bone marrow tissue samples for tumor viability and inflammatory
infiltrate; assessing residual tumor cells for antigen specificity and gene expression;
and assaying TDL for tumor reactivity and specificity.

- Investigate methods of characterizing the immune phenotypic and functional
characteristics of patient TDL and tumor-selected TDL and compare the in vitro
antitumor efficacy of these two cell products.

- Identify recombinant, graft-versus-tumor (GVT) antigens in tumor samples before and
after administration of TDL to better understand the mechanisms and effectors of GVT
response in these patients.

- Investigate methods of characterizing tumor infiltrate in these patients by evaluating
tumor and bone marrow tissue samples for viability and inflammatory infiltrate;
assessing residual tumor cells for enhanced antigen specificity and gene expression;
and assaying TDL for tumor reactivity and specificity.

- Investigate the effect of immune depletion in these patients on the availability of
homeostatic cytokines and the requirement for exogenous cytokine support of in-vivo
survival and expansion of adoptively transferred cells.

OUTLINE: This is a pilot study.

Patients undergo apheresis to collect peripheral blood mononuclear cells (PBMCs). Patients
then undergo surgical resection of accessible tumor and/or bone marrow is collected.
Tumor-infiltrating T lymphocytes (TILs) are isolated from tumor tissue, costimulated with
PBMCs, and expanded ex vivo to generate tumor-derived lymphocytes (TDLs). Beginning at least
24 days after surgery and within 7 days after tumor assessment, patients receive an infusion
of TDL IV in the absence of disease progression or unacceptable toxicity.

Patients undergo blood, bone marrow, and tissue collection periodically during study for
correlative studies, including the following: phenotypic and functional characterization of
residual tumor and TDL by immunohistochemistry and fluorescent in situ hybridization;
identification of prognostic markers of clinical outcome (i.e., HLA-A, -B, and -C; HLA-DR,
Fas ligand, CD80, and CD86) by flow cytometry; in vitro assessment of tumor-reactive,
selectively expanded T-cell clones by gene expression profiling; and evaluation of immune
response by tumor-specific cytotoxicity assays (immunoenzyme techniques) and DNA sequencing
for recombinant graft-versus-tumor antigens. Chimerism is assessed with a polymerase chain
reaction-based assay and cytogenetics.

After completion of study therapy, patients are followed periodically for at least 5 years.

PROJECTED ACCRUAL: A total of 36 patients will be accrued for this study.