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

This study has been terminated.
Sponsor:
Collaborators:
University of Pittsburgh
Amgen
Genzyme, a Sanofi Company
Information provided by:
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
ClinicalTrials.gov Identifier:
NCT00040651
First received: July 5, 2002
Last updated: December 19, 2007
Last verified: December 2007
  Purpose

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 Intervention Phase
Scleroderma
Systemic Sclerosis
Drug: Fludarabine
Drug: Cyclophosphamide
Drug: Thymoglobulin
Procedure: Leukapheresis
Procedure: Self bone marrow transplant
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: 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

Resource links provided by NLM:


Further study details as provided by National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS):

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

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

Estimated Enrollment: 15
Study Start Date: July 2002
Study Completion Date: March 2007
Primary Completion Date: March 2007 (Final data collection date for primary outcome measure)
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.

  Eligibility

Ages Eligible for Study:   18 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00040651

Locations
United States, Pennsylvania
UPMC Hillman Cancer Center
Pittsburgh, Pennsylvania, United States, 15232
Sponsors and Collaborators
University of Pittsburgh
Amgen
Genzyme, a Sanofi Company
Investigators
Principal Investigator: Robert Herberman, MD UPMC Health System
  More Information

No publications provided

ClinicalTrials.gov Identifier: NCT00040651     History of Changes
Other Study ID Numbers: N01 AR92239, NIAMS-047
Study First Received: July 5, 2002
Last Updated: December 19, 2007
Health Authority: United States: Food and Drug Administration

Keywords provided by National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS):
Systemic Sclerosis
Chemotherapy
Cyclophosphamide
Fludarabine
Leukapheresis
Mesna
Stem Cell
T-Cell
Thymoglobulin
Scleroderma

Additional relevant MeSH terms:
Scleroderma, Diffuse
Scleroderma, Systemic
Sclerosis
Connective Tissue Diseases
Pathologic Processes
Skin Diseases
Cyclophosphamide
Fludarabine
Fludarabine phosphate
Alkylating Agents
Antimetabolites
Antimetabolites, Antineoplastic
Antineoplastic Agents
Antineoplastic Agents, Alkylating
Antirheumatic Agents
Immunologic Factors
Immunosuppressive Agents
Molecular Mechanisms of Pharmacological Action
Myeloablative Agonists
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses

ClinicalTrials.gov processed this record on November 20, 2014