Stem Cell Transplantation for Metastatic Solid Tumors

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 instituted.

- INCLUSION CRITERIA:

PATIENTS:

Patients with metastatic solid tumors ( breast, cholangiocarcinoma, small
intestine/colon/rectal, adenocarcinoma, esophageal/gastric, hepatocellular, pancreatic,
prostate, bony/soft tissue sarcomas, which are histologically confirmed, progressive and
incurable.

Due to low accrual, effective 12/19/2006, patients with adrenal, basal cell, transitional
cell carcinoma of the bladder or uroepithelium, ovarian, small cell lung cancer, non small
cell lung cancer, and adenocarcinomas of unknown primary origin are no longer eligible for
the trial.

Age greater than or equal to 10 to less than or equal to 80.

No known standard therapy for the patient's disease that is potentially curative or
definitely capable of extending life expectancy.

Metastatic disease, which is bi-dimensionally evaluable radiographically.

No prior treatment for neoplasm within 30 days.



Ability to comprehend the investigational nature of the study and provide informed consent.

Availability of HLA identical or single HLA-locus mismatched family donor.



Willingness and availability to return to the NIH for scheduled follow-ups.

DONOR:

HLA identical or single HLA-locus mismatched family donor.

Age greater than or equal to 10 up to 80 years old.

Ability to comprehend the investigational nature of the study and provide informed consent.

EXCLUSION CRITERIA:

PATIENT:

Pregnant or lactating.

Age less than 10 or greater than 80 years.

ECOG performance status of 3 or more.

Psychiatric disorder or mental deficiency severe as to make compliance with the BMT
treatment unlikely, and making informed consent impossible.

Major anticipated illness or organ failure incompatible with survival from PBSC transplant.

DLCO: less than 40% predicted.

Left ventricular ejection fraction: less than 30%.

Serum creatinine greater than 2.5mg/dl or creatinine clearance less than 50 cc/min by 24 hr
urine collection.

Serum bilirubin greater than 4 mg/dl

Transaminases greater than 5 times the upper limit of normal.

Oral intake less than 1,200 calories/day.

Recent weight loss of greater than or equal to 10% of actual body weight.

Life expectancy less than 3 months

Therapy for malignancy within 4 weeks of beginning protocol.

CNS metastatic disease associated with intracranial bleeding, uncontrolled seizure disorder
or significant intracranial mass effect.



Other malignant diseases liable to relapse or progress within 5 years.



Uncontrolled infection.

DONOR:

Pregnant or lactating.

Donor unfit to receive G-CSF and undergo apheresis. (Uncontrolled hypertension, history of
congestive heart failure or unstable angina, thrombocytopenia).

Age less than 10 or greater than 80 years.

HIV positive. Donors who are positive for HBV, HCV or HTLV-I may be used at the discretion
of the investigator following counseling and approval from the recipient.