Exploratory Study of Non-Myeloablative Allogeneic Peripheral Blood Stem Cell and Donor Lymphocyte Infusions for Metastatic Neoplasms Refractory to Standard Therapy
10 Years
80 Years
Both
Breast Cancer, Carcinoma of Unknown Primary, Colorectal Cancer, Esophageal Cancer, Gallbladder Cancer, Gastric Cancer, Liver Cancer, Lung Cancer, Pancreatic Cancer, Prostate Cancer, Sarcoma
Trial Information
Exploratory Study of Non-Myeloablative Allogeneic Peripheral Blood Stem Cell and Donor Lymphocyte Infusions for Metastatic Neoplasms Refractory to Standard Therapy
OBJECTIVES:
Primary:
- Identify an anti-tumor effect of allogeneic peripheral blood stem cell transplantation
by induction of a graft-versus-tumor effect in patients with a diversity of metastatic
solid tumors refractory to standard therapy.
Secondary:
- Determine engraftment in these patients.
- Determine the effects of donor lymphocyte infusion and cyclosporine withdrawal on tumor
regression in these patients.
OUTLINE: Patients are stratified according to risk of graft rejection, which determines the
preparative regimen received. High-risk patients include heavily transfused patients or
patients who have received donor-directed blood products and single HLA-locus mismatched
patients.
Preparative regimen: Patients receive cyclophosphamide IV over 1 hour on days -7 and -6 and
fludarabine IV over 30 minutes on days -5 to -1. Patients at high risk also receive
antithymocyte globulin IV on days -5 to -2.
Patients undergo allogeneic peripheral blood stem cell transplantation on day 0. Patients
receive cyclosporine either by continuous infusion IV or orally twice a day on days -4 to
100 as graft-versus-host disease (GVHD) prophylaxis.
Patients with less than 100% donor T-cell chimerism or with evidence of tumor progression
receive donor lymphocytes after day 100, every 4 weeks, until 100% donor T-cell chimerism,
disease regression, and/or GVHD occurs.
Patients are followed at 4, 6, 8, 10, and 12 months, every 3 months for 2 years, and then
every 6 months for 2 years.
PROJECTED ACCRUAL: Approximately 150 patients (10 for each cancer) will be accrued for this
study.
Inclusion Criteria
DISEASE CHARACTERISTICS:
- Histologically proven progressive and incurable metastatic solid tumors
- Hepatocellular carcinoma
- Pancreatic carcinoma
- Cholangiocarcinoma
- Esophageal carcinoma
- Gastric carcinoma
- Colon and rectal carcinoma
- Breast carcinoma
- Hormone-refractory prostate carcinoma
- Soft tissue sarcomas
- Bony sarcomas
- Refractory to standard therapy or no known curative therapy exists
- Bidimensionally evaluable metastatic disease by radiography
- HLA-identical or single HLA-locus mismatched family donor available
- No CNS metastases associated with intracranial bleeding, uncontrolled seizure
disorder, or significant intracranial mass effect
- Hormone receptor status:
- Not specified
PATIENT CHARACTERISTICS:
Age:
- 10 to 80
Sex:
- Not specified
Menopausal status:
- Not specified
Performance status:
- ECOG 0-2
Life expectancy:
- At least 3 months
Hematopoietic:
- Not specified
Hepatic:
- Bilirubin no greater than 4 mg/dL
- SGOT/SGPT no greater than 5 times upper limit of normal
Renal:
- Creatinine no greater than 2.5 mg/dL
Cardiovascular:
- LVEF at least 30%
Pulmonary:
- DLCO at least 40% predicted
Other:
- Not pregnant or nursing
- No psychiatric disorder or severe mental deficiency
- No other major illness or organ failure
- Oral intake at least 1,200 calories/day
- No recent weight loss of 10% or more
- No other malignant diseases liable to relapse or progress within 5 years
- No uncontrolled infection
PRIOR CONCURRENT THERAPY:
Biologic therapy:
- Not specified
Chemotherapy:
- Not specified
Endocrine therapy:
- Not specified
Radiotherapy:
- Not specified
Surgery:
- Not specified
Other:
- At least 30 days since prior cancer therapy
Type of Study:
Interventional
Study Design:
Primary Purpose: Treatment
Outcome Measure:
Tumor response (i.e., complete response, partial response, stable disease, or progressive disease)
Safety Issue:
No
Principal Investigator
Richard W. Childs, MD
Investigator Role:
Study Chair
Investigator Affiliation:
National Heart, Lung, and Blood Institute (NHLBI)
Authority:
United States: Federal Government
Study ID:
CDR0000066997
NCT ID:
NCT00003839
Start Date:
March 1999
Completion Date:
Related Keywords:
- Breast Cancer
- Carcinoma of Unknown Primary
- Colorectal Cancer
- Esophageal Cancer
- Gallbladder Cancer
- Gastric Cancer
- Liver Cancer
- Lung Cancer
- Pancreatic Cancer
- Prostate Cancer
- Sarcoma
- stage IV colon cancer
- stage IV breast cancer
- recurrent breast cancer
- stage IV gastric cancer
- recurrent gastric cancer
- metastatic osteosarcoma
- stage II pancreatic cancer
- stage III pancreatic cancer
- recurrent pancreatic cancer
- stage IV rectal cancer
- recurrent colon cancer
- recurrent rectal cancer
- stage II esophageal cancer
- stage III esophageal cancer
- stage IV esophageal cancer
- recurrent esophageal cancer
- stage IV adult soft tissue sarcoma
- recurrent adult soft tissue sarcoma
- stage IV childhood liver cancer
- recurrent childhood liver cancer
- advanced adult primary liver cancer
- recurrent adult primary liver cancer
- recurrent osteosarcoma
- unresectable gallbladder cancer
- recurrent gallbladder cancer
- recurrent prostate cancer
- childhood hepatocellular carcinoma
- adult primary hepatocellular carcinoma
- metastatic childhood soft tissue sarcoma
- recurrent childhood soft tissue sarcoma
- adenocarcinoma of unknown primary
- cholangiocarcinoma of the gallbladder
- stage IV uterine sarcoma
- recurrent uterine sarcoma
- stage IV prostate cancer
- recurrent non-small cell lung cancer
- stage IV pancreatic cancer
- Breast Neoplasms
- Carcinoma
- Colorectal Neoplasms
- Esophageal Diseases
- Esophageal Neoplasms
- Liver Neoplasms
- Lung Neoplasms
- Stomach Neoplasms
- Pancreatic Neoplasms
- Prostatic Neoplasms
- Gallbladder Neoplasms
- Neoplasms, Unknown Primary
- Sarcoma
Name | Location |
|---|---|
| NIH - Warren Grant Magnuson Clinical Center | Bethesda, Maryland 20892-1182 |
