Exploratory Study of Non-Myeloablative Allogeneic Stem Cell Transplantation and Donor Lymphocyte Infusions for Metastatic Neoplasms Refractory to Standard Therapy
The main objective of this study is to identify metastatic neoplasms, which may be
susceptible to the GVT effect. We will treat patients with progressive metastatic solid
tumors refractory to standard therapy with a non-myeloablative allogeneic PBSC transplant
from a family donor. A GVT effect from immunocompetent donor immune cells could extend life
expectancy and possibly cure such patients.
Eligible patients will be treated with an allogeneic peripheral blood stem cell transplant
from an HLA identical or single HLA antigen-mismatched family donor, using an intensive
immunosuppressive regimen without myeloablation ("mini-transplant") in an attempt to
decrease the transplant related toxicities while preserving the anti-malignancy and/or
anti-host marrow effect of the graft. The low intensity non-myeloablative conditioning
regimen should provide adequate immunosuppression to allow stem cell and lymphocyte
engraftment. A T-cell replete, donor-derived, granulocyte colony stimulating factor
(G-CSF)-mobilized peripheral blood stem cells (PBSC) will be used to establish hematopoietic
and lymphoid reconstitution. We will infuse lymphocytes in patients with < 100% donor
T-cell chimerism or with evidence of tumor progression in an attempt to prevent graft
rejection and enhance a graft-versus-malignancy effect, respectively.
This trial is open to several different types of metastatic, treatment-refractory, solid
neoplasms, breast, cholangiocarcinoma, small intestine/colon/rectal adenocarcinoma,
esophageal/gastric, hepatocellular, pancreatic, prostate, and bony/soft tissue sarcomas.
The trial design permits up to 10 patients with a specific tumor type to be enrolled to
screen for anti-tumor effects. A single complete response in a specific tumor type is an
indication to exclude further patients with that diagnosis from the study. Subsequently, a
new protocol which focuses on further defining a GVT effect in that disease category will be
To identify an anti-tumor effect of allogeneic PBSC transplantation by induction of a graft-versus-tumor (GVT) effect in patients with a diversity of metastatic solid tumors, which are refractory to standard therapy.
Richard W Childs, M.D.
National Heart, Lung, and Blood Institute (NHLBI)
United States: Federal Government
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