Clinical trial NCT00040651: Safety and Value of Self Bone Marrow Transplants Following Chemotherapy in Scleroderma Patients
Official title: Transplantation With T-Cell Depleted Autologous Peripheral Stem Cells for Severe Systemic Sclerosis: A Phase I Dose Escalation Study
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Scleroderma
Systemic Sclerosis
Keywords: Systemic Sclerosis
Chemotherapy
Cyclophosphamide
Fludarabine
Leukapheresis
Mesna
Stem Cell
T-Cell
Thymoglobulin
Scleroderma
Lead sponsor: National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Sponsor class: NIH
Collaborators: name: University of Pittsburgh
name: Amgen
name: Genzyme, a Sanofi Company
First posted: 2002-07-10
Enrollment: 15
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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 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

Primary outcomes:
measure: Non-hematologic toxicity experienced
timeFrame: Measured within 3 weeks after transplant
Secondary outcomes:
measure: Clinical and laboratory responses to chemotherapy and self bone marrow transplant
timeFrame: Measured at 12 and 24 months after transplant
Other outcomes:
Locations:
city: Pittsburgh
country: United States
facility: UPMC Hillman Cancer Center
state: Pennsylvania
Study officials:
affiliation: UPMC Health System
name: Robert Herberman, MD
role: PRINCIPAL_INVESTIGATOR
References: