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

December 19, 2007 updated by: National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)

Transplantation With T-Cell Depleted Autologous Peripheral Stem Cells for Severe Systemic Sclerosis: A Phase I Dose Escalation Study

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.

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment

15

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Pennsylvania
      • Pittsburgh, Pennsylvania, United States, 15232
        • UPMC Hillman Cancer Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 70 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Non-hematologic toxicity experienced
Time Frame: Measured within 3 weeks after transplant
Measured within 3 weeks after transplant

Secondary Outcome Measures

Outcome Measure
Time Frame
Clinical and laboratory responses to chemotherapy and self bone marrow transplant
Time Frame: Measured at 12 and 24 months after transplant
Measured at 12 and 24 months after transplant

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)

Collaborators

University of Pittsburgh
Genzyme, a Sanofi Company
Amgen

Investigators

  • Principal Investigator: Robert Herberman, MD, UPMC Health System

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

July 1, 2002

Primary Completion (Actual)

March 1, 2007

Study Completion (Actual)

March 1, 2007

Study Registration Dates

First Submitted

July 5, 2002

First Submitted That Met QC Criteria

July 9, 2002

First Posted (Estimate)

July 10, 2002

Study Record Updates

Last Update Posted (Estimate)

December 28, 2007

Last Update Submitted That Met QC Criteria

December 19, 2007

Last Verified

December 1, 2007

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • N01 AR92239
  • NIAMS-047

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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