Peripheral Stem Cell Transplant and White Blood Cell Transfusions in Treating Patients With Refractory Metastatic Solid Tumors - Full Text View

Sponsored by:	National Heart, Lung, and Blood Institute (NHLBI)
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00003839

Purpose

RATIONALE: Giving low doses of chemotherapy, such as cyclophosphamide and fludarabine, before a donor peripheral blood stem cell transplant helps stop the growth of tumor cells. It also stops the patient's immune system from rejecting the donor's stem cells. The donated stem cells may replace the patient's immune system and help destroy any remaining tumor cells (graft-versus-tumor effect). Giving an infusion of the donor's T cells (donor lymphocyte infusion) after the transplant may help increase this effect. Sometimes the transplanted cells from a donor can also make an immune response against the body's normal cells. Giving antithymocyte globulin before the transplant and cyclosporine after the transplant may stop this from happening.

PURPOSE: This phase II trial is studying how well cyclophosphamide, fludarabine, antithymocyte globulin, and peripheral stem cell transplant followed by cyclosporin and donor white blood cell transfusions work in treating patients with refractory metastatic solid tumors.

Condition	Intervention	Phase
Breast Cancer Carcinoma of Unknown Primary Colorectal Cancer Esophageal Cancer Gallbladder Cancer Gastric Cancer Liver Cancer Lung Cancer Pancreatic Cancer Prostate Cancer Sarcoma	Biological: anti-thymocyte globulin Biological: therapeutic allogeneic lymphocytes Drug: cyclophosphamide Drug: cyclosporine Drug: fludarabine phosphate Procedure: peripheral blood stem cell transplantation	Phase II

Study Type:	Interventional
Study Design:	Treatment
Official Title:	Exploratory Study of Non-Myeloablative Allogeneic Peripheral Blood Stem Cell and Donor Lymphocyte Infusions for Metastatic Neoplasms Refractory to Standard Therapy

Resource links provided by NLM:

Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:

Tumor response (i.e., complete response, partial response, stable disease, or progressive disease) [ Designated as safety issue: No ]

Secondary Outcome Measures:

Engraftment [ Designated as safety issue: No ]
Acute and chronic graft-versus-host disease [ Designated as safety issue: Yes ]
Transplant-related morbidity and mortality [ Designated as safety issue: Yes ]
Graft-vs-tumor effect as measured by CAT scans at days 30, 60, and 100 following transplant [ Designated as safety issue: No ]
Disease-free survival as measured by CAT scans at 6 months and 1 year [ Designated as safety issue: No ]

Estimated Enrollment:	150
Study Start Date:	March 1999
Estimated Primary Completion Date:	December 2009 (Final data collection date for primary outcome measure)

Detailed Description:

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.

Eligibility

Ages Eligible for Study:	10 Years to 80 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00003839

Locations

United States, Maryland
NIH - Warren Grant Magnuson Clinical Center
Bethesda, Maryland, United States, 20892-1182

Sponsors and Collaborators

National Heart, Lung, and Blood Institute (NHLBI)

Investigators

Study Chair:

Richard W. Childs, MD

National Heart, Lung, and Blood Institute (NHLBI)

More Information

Additional Information:

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

Publications:

Gorak E, Geller N, Srinivasan R, Espinoza-Delgado I, Donohue T, Barrett AJ, Suffredini A, Childs R. Engraftment syndrome after nonmyeloablative allogeneic hematopoietic stem cell transplantation: incidence and effects on survival. Biol Blood Marrow Transplant. 2005 Jul;11(7):542-50.

Srinivasan R, Balow JE, Sabnis S, Lundqvist A, Igarashi T, Takahashi Y, Austin H, Tisdale J, Barrett J, Geller N, Childs R. Nephrotic syndrome: an under-recognised immune-mediated complication of non-myeloablative allogeneic haematopoietic cell transplantation. Br J Haematol. 2005 Oct;131(1):74-9.

Carvallo C, Geller N, Kurlander R, Srinivasan R, Mena O, Igarashi T, Griffith LM, Linehan WM, Childs RW. Prior chemotherapy and allograft CD34+ dose impact donor engraftment following nonmyeloablative allogeneic stem cell transplantation in patients with solid tumors. Blood. 2004 Feb 15;103(4):1560-3. Epub 2003 Oct 9.

Childs RW, Barrett J. Nonmyeloablative allogeneic immunotherapy for solid tumors. Annu Rev Med. 2004;55:459-75. Review.

Espinoza-Delgado I, Childs RW. Nonmyeloablative transplantation for solid tumors: a new frontier for allogeneic immunotherapy. Expert Rev Anticancer Ther. 2004 Oct;4(5):865-75. Review.

Childs R, Srinivasan R. Advances in allogeneic stem cell transplantation: directing graft-versus-leukemia at solid tumors. Cancer J. 2002 Jan-Feb;8(1):2-11. Review.

Nakamura R, Cortez K, Solomon S, Battiwalla M, Gill VJ, Hensel N, Childs R, Barrett AJ. High-dose acyclovir and pre-emptive ganciclovir to prevent cytomegalovirus disease in myeloablative and non-myeloablative allogeneic stem cell transplantation. Bone Marrow Transplant. 2002 Aug;30(4):235-42.

Childs RW. Evolving trends in hematopoietic cell transplantation for solid tumors: tempering enthusiasm with clinical reality. Ann Oncol. 2004 Apr;15(4):543-4. No abstract available.

Barrett J, Childs R. New directions in allogeneic stem cell transplantation. Semin Hematol. 2002 Jan;39(1):1-2. No abstract available.

Childs R, Barrett J. Nonmyeloablative stem cell transplantation for solid tumors: expanding the application of allogeneic immunotherapy. Semin Hematol. 2002 Jan;39(1):63-71. Review.

Childs RW. Immunotherapy of solid tumors: nonmyeloablative allogeneic stem cell transplantation. MedGenMed. 2002 Jun 26;4(3):13. Review. No abstract available.

Graber C, de Almeider KN, Childs R, Barrett AJ, Gill VJ, Bennett JE. CMV reactivation in nonmyeloablative HSCT. Bone Marrow Transplant. 2001 Apr;27(7):775. No abstract available.

Barrett J, Childs R. Non-myeloablative stem cell transplants. Br J Haematol. 2000 Oct;111(1):6-17. Review. No abstract available.

Barrett J, Childs R. The benefits of an alloresponse: graft-versus-tumor. J Hematother Stem Cell Res. 2000 Jun;9(3):347-54. Review. No abstract available.

Responsible Party:	National Heart, Lung, and Blood Institute ( Richard W. Childs )
Study ID Numbers:	CDR0000066997, NHLBI-99-H-0064
Study First Received:	November 1, 1999
Last Updated:	February 6, 2009
ClinicalTrials.gov Identifier:	NCT00003839 History of Changes
Health Authority:	United States: Federal Government

Keywords provided by National Cancer Institute (NCI):

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

Study placed in the following topic categories:

Gallbladder Diseases
Thoracic Neoplasms
Anti-Infective Agents
Liver Diseases
Cyclosporine
Prostatic Diseases
Rectal Neoplasms
Carcinoma, Hepatocellular
Pancreatic Neoplasms
Colonic Diseases
Urogenital Neoplasms
Cyclosporins
Rectal Diseases
Neoplasms, Connective and Soft Tissue
Lung Neoplasms

Neoplasm Metastasis
Osteogenic Sarcoma
Breast Diseases
Endocrine Gland Neoplasms
Neoplasms, Unknown Primary
Digestive System Neoplasms
Breast Neoplasms
Endocrine System Diseases
Esophageal Cancer
Genital Diseases, Male
Carcinoma
Malignant Mesenchymal Tumor
Esophageal Disorder
Uterine Sarcoma
Lung Diseases

Additional relevant MeSH terms:

Gallbladder Diseases
Thoracic Neoplasms
Anti-Infective Agents
Liver Diseases
Antimetabolites, Antineoplastic
Cyclosporine
Molecular Mechanisms of Pharmacological Action
Prostatic Diseases
Pancreatic Neoplasms
Physiological Effects of Drugs
Colonic Diseases
Urogenital Neoplasms
Cyclosporins
Rectal Diseases
Neoplasms, Connective and Soft Tissue

Neoplasms by Site
Pathologic Processes
Lung Neoplasms
Therapeutic Uses
Neoplasm Metastasis
Dermatologic Agents
Breast Diseases
Endocrine Gland Neoplasms
Neoplasms, Unknown Primary
Digestive System Neoplasms
Breast Neoplasms
Endocrine System Diseases
Genital Diseases, Male
Carcinoma
Neoplasms

ClinicalTrials.gov processed this record on September 01, 2009