Expired Study
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Bethesda, Maryland 20892


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.


Study summary:

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.


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


Study is Available At:


Original ID:

CDR0000066997


NCT ID:

NCT00003839


Secondary ID:

NHLBI-99-H-0064


Study Acronym:


Brief Title:

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


Official Title:

Exploratory Study of Non-Myeloablative Allogeneic Peripheral Blood Stem Cell and Donor Lymphocyte Infusions for Metastatic Neoplasms Refractory to Standard Therapy


Overall Status:

Active, not recruiting


Study Phase:

Phase 2


Genders:

Both


Minimum Age:

10 Years


Maximum Age:

80 Years


Quick Facts

Healthy Volunteers
Oversight Has DMC
Study Is FDA Regulated
Study Is Section 801
Has Expanded Access

Study Source:

National Cancer Institute (NCI)


Oversight Authority:

There was an error processing this request


Reasons Why Stopped:


Study Type:

Interventional


Study Design:

Primary Purpose: Treatment


Number of Arms:

1


Number of Groups:

0


Total Enrollment:

150


Enrollment Type:

Anticipated


Overall Contact Information

Official Name:Richard W. Childs, MD
Study Chair
National Heart, Lung, and Blood Institute (NHLBI)

Study Dates

Start Date:March 1999
Primary Completion Date:December 2009
Primary Completion Type:Anticipated
Verification Date:November 2008
Last Changed Date:February 6, 2009
First Received Date:November 1, 1999

Study Outcomes

Outcome Type:Primary Outcome
Measure:Tumor response (i.e., complete response, partial response, stable disease, or progressive disease)
Safety Issues:False
Outcome Type:Secondary Outcome
Measure:Engraftment
Safety Issues:False
Outcome Type:Secondary Outcome
Measure:Acute and chronic graft-versus-host disease
Safety Issues:True
Outcome Type:Secondary Outcome
Measure:Transplant-related morbidity and mortality
Safety Issues:True
Outcome Type:Secondary Outcome
Measure:Graft-vs-tumor effect as measured by CAT scans at days 30, 60, and 100 following transplant
Safety Issues:False
Outcome Type:Secondary Outcome
Measure:Disease-free survival as measured by CAT scans at 6 months and 1 year
Safety Issues:False

Study Interventions

Intervention Type:Biological
Name:anti-thymocyte globulin
Intervention Type:Biological
Name:therapeutic allogeneic lymphocytes
Intervention Type:Drug
Name:cyclophosphamide
Intervention Type:Drug
Name:cyclosporine
Intervention Type:Drug
Name:fludarabine phosphate
Intervention Type:Procedure
Name:peripheral blood stem cell transplantation

Study Arms

There are no available Study Arms

Study Agencies

Agency Class:NIH
Agency Type:Lead Sponsor
Agency Name:National Heart, Lung, and Blood Institute (NHLBI)

Sample and Retention Information

There are no available Sample and Retention Information

Study References

Reference Type:Reference
Citation: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.
PMID:15983554
Reference Type:Reference
Citation: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.
PMID:16173966
Reference Type:Reference
Citation: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.
PMID:14551148
Reference Type:Reference
Citation:Childs RW, Barrett J. Nonmyeloablative allogeneic immunotherapy for solid tumors. Annu Rev Med. 2004;55:459-75. Review.
PMID:14746531
Reference Type:Reference
Citation: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.
PMID:15485320
Reference Type:Reference
Citation: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.
PMID:11895199
Reference Type:Reference
Citation: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.
PMID:12203140
Reference Type:Reference
Citation: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.
PMID:15033656
Reference Type:Reference
Citation:Barrett J, Childs R. New directions in allogeneic stem cell transplantation. Semin Hematol. 2002 Jan;39(1):1-2. No abstract available.
PMID:11799523
Reference Type:Reference
Citation: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.
PMID:11799531
Reference Type:Reference
Citation:Childs RW. Immunotherapy of solid tumors: nonmyeloablative allogeneic stem cell transplantation. MedGenMed. 2002 Jun 26;4(3):13. Review. No abstract available.
PMID:12466756
Reference Type:Reference
Citation: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.
PMID:11360122
Reference Type:Reference
Citation:Barrett J, Childs R. Non-myeloablative stem cell transplants. Br J Haematol. 2000 Oct;111(1):6-17. Review. No abstract available.
PMID:11091178
Reference Type:Reference
Citation: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.
PMID:10894356

Data Source: ClinicalTrials.gov

Date Processed: January 21, 2020

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