Tumor-Infiltrating Lymphocytes in Treating Patients With Persistent or Recurrent B-Cell Non-Hodgkin's Lymphoma, Hodgkin's Lymphoma, Chronic Lymphocytic Leukemia or Multiple Myeloma After a Previous Donor Stem Cell Transplant

2014-08-27 03:39:44 | BioPortfolio


RATIONALE: Biological therapies, such as cellular adoptive immunotherapy using tumor-infiltrating lymphocytes, may stimulate the immune system in different ways and stop cancer cells from growing.

PURPOSE: This phase I trial is studying the side effects and how well tumor-infiltrating lymphocytes work in treating patients with persistent or recurrent B-cell non-Hodgkin's lymphoma, Hodgkin's lymphoma, chronic lymphocytic leukemia, or multiple myeloma after a previous donor stem cell transplant.




- 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.


- 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.

Study Design

Primary Purpose: Treatment




graft-versus-tumor induction therapy, therapeutic tumor infiltrating lymphocytes, cytogenetic analysis, fluorescence in situ hybridization, microarray analysis, polymerase chain reaction, flow cytometry, immunoenzyme technique, immunohistochemistry staini


Warren Grant Magnuson Clinical Center - NCI Clinical Trials Referral Office
United States




National Cancer Institute (NCI)

Results (where available)

View Results


Published on BioPortfolio: 2014-08-27T03:39:44-0400

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Medical and Biotech [MESH] Definitions

Hypoxic conditions in tumor cells due to the tumor outgrowing its blood supply. It is associated with increased METASTASIS and resistance to RADIOTHERAPY and DRUG THERAPY.

Immunological rejection of tumor tissue/cells following bone marrow transplantation.

Lymphocytes that show specificity for autologous tumor cells. Ex vivo isolation and culturing of TIL with interleukin-2, followed by reinfusion into the patient, is one form of adoptive immunotherapy of cancer.

Form of adoptive transfer where cells with antitumor activity are transferred to the tumor-bearing host in order to mediate tumor regression. The lymphoid cells commonly used are lymphokine-activated killer (LAK) cells and tumor-infiltrating lymphocytes (TIL). This is usually considered a form of passive immunotherapy. (From DeVita, et al., Cancer, 1993, pp.305-7, 314)

A benign, rapidly growing, deeply pigmented tumor of the jaw and occasionally of other sites, consisting of an infiltrating mass of cells arranged in an alveolar pattern, and occurring almost exclusively in infants. Its source of origin is in dispute, the various theories giving rise to its several names. (Dorland, 27th ed)

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