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Safety and Value of Self Bone Marrow Transplants Following Chemotherapy in Scleroderma Patients

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00040651
Recruitment Status : Terminated
First Posted : July 10, 2002
Last Update Posted : December 28, 2007
University of Pittsburgh
Genzyme, a Sanofi Company
Information provided by:
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)

Brief Summary:
Scleroderma, or systemic sclerosis (SSc), is a diffuse connective tissue disease characterized by changes in the skin, blood vessels, skeletal muscles, and internal organs. The purpose of this study is to determine the safety and value of self bone marrow transplants after chemotherapy in patients with severe SSc.

Condition or disease Intervention/treatment Phase
Scleroderma Systemic Sclerosis Drug: Fludarabine Drug: Cyclophosphamide Drug: Thymoglobulin Procedure: Leukapheresis Procedure: Self bone marrow transplant Phase 1

Detailed Description:

SSc is a chronic disease involving the abnormal growth of connective tissue, which supports the skin and internal organs. This disease can affect the skin, making it hard and tight; it can also damage the blood vessels and internal organs such as the heart, lungs, and kidneys. Initially, precursor blood cells will be mobilized from the bone marrow into the blood stream after chemotherapy and white blood cell growth factors are administered. These precursors (or autologous stem cells) can be harvested from the bloodstream in a procedure called leukapheresis; it is the precursor blood cells that are transplanted back into the patient's body after high dose chemotherapy. Autologous stem cells are preferred over donor bone marrow because there is no risk of rejection. This study will evaluate the safety and effectiveness of self bone marrow transplants after intravenous chemotherapy in patients with SSc.

Prior to transplantation, patients will undergo diphtheria/tetanus (DT) vaccination and blood collection. Two weeks after vaccination, patients will have a Hickman catheter inserted into their bodies and will be admitted to the hospital to receive mobilization chemotherapy with intravenous (IV) cyclophosphamide. Patients will be discharged after receiving the cyclophosphamide therapy with the understanding that they must stay locally and must return to the outpatient clinic daily to have blood samples drawn and to receive an injection of a growth factor, G-CSF, in stimulate blood cell production. Patients will undergo leukapheresis at the clinic when their white blood cell (WBC) counts reach 2500 cells/mm3 or more. A machine called the Nexell Isolex 300i will be used to remove T-cells from the cells collected by leukapheresis.

After leukapheresis and other pre-transplant procedures have been completed, patients will be hospitalized for approximately 14 to 21 days. On Days 1 through 5 of hospitalization, patients will receive IV fludarabine and one of several possible dose levels of cyclophosphamide. On Days 3 through 5, patients will receive IV thymoglobulin to kill the T-cells that cause the damage from systemic sclerosis. On Day 8, patients will receive their own stem cells from the previous leukapheresis procedure. While in the hospital, patients will be monitored by daily blood collection and will not be discharged until their white blood cell counts return to a safe, stable level. Prior to discharge from the hospital, patients will undergo a second leukapheresis.

Patients are required to stay locally in Pittsburgh up to 100 days post-transplantation. Study visits will occur at the clinic every week for the first three months after transplant and again at 4, 5, 6, 9, 12, 18, and 24 months post-transplantation. Study visits will include a physical exam and blood collection; patients will be also asked to complete a questionnaire. Patients will undergo an electrocardiogram (EKG) at Month 1, a chest x-ray at Month 6, 24-hour urine collection at Months 6 and 18, and pulmonary tests at Months 6, 12, and 24. Additional leukapheresis will be conducted at 12 and 24 months post-transplant to assess patients' health.

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Study Type : Interventional  (Clinical Trial)
Enrollment : 15 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Transplantation With T-Cell Depleted Autologous Peripheral Stem Cells for Severe Systemic Sclerosis: A Phase I Dose Escalation Study
Study Start Date : July 2002
Actual Primary Completion Date : March 2007
Actual Study Completion Date : March 2007

Primary Outcome Measures :
  1. Non-hematologic toxicity experienced [ Time Frame: Measured within 3 weeks after transplant ]

Secondary Outcome Measures :
  1. Clinical and laboratory responses to chemotherapy and self bone marrow transplant [ Time Frame: Measured at 12 and 24 months after transplant ]

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

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Ages Eligible for Study:   18 Years to 70 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • ECOG performance status of 0 to 2
  • Willing to participate in all portions of the protocol, including pharmacodynamic and immunologic studies and patient care follow-up visits
  • Willing to stay in the Pittsburgh area for 100 days post-transplantation
  • Willing to use acceptable methods of contraception

Exclusion Criteria:

  • HIV infected
  • Hepatitis C virus infected
  • Active infection
  • Small malabsorption syndrome
  • Immunosuppressive therapy other than steroids within 4 weeks of study entry
  • Pregnant or breastfeeding

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00040651

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United States, Pennsylvania
UPMC Hillman Cancer Center
Pittsburgh, Pennsylvania, United States, 15232
Sponsors and Collaborators
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
University of Pittsburgh
Genzyme, a Sanofi Company
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Principal Investigator: Robert Herberman, MD UPMC Health System
Layout table for additonal information Identifier: NCT00040651    
Other Study ID Numbers: N01 AR92239
First Posted: July 10, 2002    Key Record Dates
Last Update Posted: December 28, 2007
Last Verified: December 2007
Keywords provided by National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS):
Systemic Sclerosis
Stem Cell
Additional relevant MeSH terms:
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Scleroderma, Systemic
Scleroderma, Diffuse
Pathologic Processes
Connective Tissue Diseases
Skin Diseases
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists