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

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	Drug: anti-thymocyte globulin Drug: cyclophosphamide Drug: cyclosporine Drug: fludarabine phosphate Drug: therapeutic allogeneic lymphocytes Procedure: peripheral blood stem cell transplantation	Phase II

Genetics Home Reference related topics:

breast cancer

MedlinePlus related topics:

Blood Transfusion and Donation Breast Cancer Cancer Colorectal Cancer Esophageal Cancer Esophagus Disorders Liver Cancer Lung Cancer Pancreatic Cancer Prostate Cancer Soft Tissue Sarcoma Stomach Cancer

Drug Information available for:

Cyclophosphamide Fludarabine Fludarabine monophosphate Cyclosporine Cyclosporin

U.S. FDA Resources

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

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

Primary Outcome Measures:

Graft vs tumor effect as measured by CAT scans at days 30, 60, and 100 following transplant [ Designated as safety issue: No ]

Secondary Outcome Measures:

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:

Determine the efficacy of allogeneic peripheral blood stem cell transplantation by induction of a graft-versus-tumor effect in patients with refractory metastatic solid tumors.
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	Recruiting
	Bethesda, Maryland, United States, 20892-1182
	Contact: Patient Recruitment 800-411-1222

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

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.

Study ID Numbers:	CDR0000066997, NHLBI-99-H-0064
First Received:	November 1, 1999
Last Updated:	July 23, 2008
ClinicalTrials.gov Identifier:	NCT00003839
Health Authority:	Unspecified

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:

Thoracic Neoplasms

Gallbladder Diseases

Liver Diseases

Cyclosporine

Prostatic Diseases

Carcinoma, Hepatocellular

Miconazole

Pancreatic Neoplasms

Malignant mesenchymal tumor

Colonic Diseases

Urogenital Neoplasms

Cyclosporins

Osteogenic sarcoma

Rectal Diseases

Neoplasms, Connective and Soft Tissue

Lung Neoplasms

Neoplasm Metastasis

Rectal cancer

Breast Diseases

Endocrine Gland Neoplasms

Non-small cell lung cancer

Neoplasms, Unknown Primary

Digestive System Neoplasms

Breast Neoplasms

Endocrine System Diseases

Stomach cancer

Genital Diseases, Male

Gall bladder cancer

Carcinoma

Lung Diseases

Additional relevant MeSH terms:

Antimetabolites

Anti-Infective Agents

Respiratory Tract Neoplasms

Antimetabolites, Antineoplastic

Neoplasms by Histologic Type

Molecular Mechanisms of Pharmacological Action

Immunologic Factors

Antineoplastic Agents

Physiological Effects of Drugs

Enzyme Inhibitors

Immunosuppressive Agents

Pharmacologic Actions

Neoplasms

Neoplastic Processes

Neoplasms by Site

Pathologic Processes

Antifungal Agents

Therapeutic Uses

Myeloablative Agonists

Antineoplastic Agents, Alkylating

Antirheumatic Agents

Dermatologic Agents

Alkylating Agents

ClinicalTrials.gov processed this record on November 20, 2008

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