Clinical trial NCT00622895
Conditions: Systemic Scleroderma Severe Systemic Sclerosis
Keywords: scleroderma systemic sclerosis
Sponsor: Fred Hutchinson Cancer Center
Start date: 2006-09-01; Completion date: 2017-08-01
Enrollment: 3 participants; Allocation: NA; Intervention model: SINGLE_GROUP

Brief summary:
The purpose of the study is to examine the safety and effectiveness of a reduced intensity conditioning regimen and allogeneic bone marrow transplant for people with systemic sclerosis. In an allogeneic bone marrow transplant procedure, bone marrow is taken from a healthy donor and transplanted into the patient. Bone marrow can be donated by a family member or an unrelated donor who is a complete tissue type match.

Participants will receive the chemotherapy and low dose radiation conditioning regimen consisting of the following: Fludarabine will be given intravenously for 5 days. Cyclophosphamide will be given intravenously on the first and second day. After completing the fludarabine and cyclophosphamide, patients will receive a single low dose of total body irradiation. The next day, patients will receive the allogeneic bone marrow transplant. On the third and fourth day after the transplant, patients will receive high dose intravenous cyclophosphamide. This is given to help prevent two complications: (1) graft rejection, which occurs when the body's immune system rejects the donor bone marrow, and (2) graft-versus-host disease (GVHD), which is when the donor immune cells attack the patient's normal tissues. On the fifth day after the transplant, patients will start receiving two additional medications: tacrolimus and mycophenolic acid (MPA, Myfortic), to help prevent GVHD. Patients will receive mycophenolic acid for about 5 weeks and tacrolimus for about 6 months. Also beginning on the fifth day after the transplant, patients will receive daily injections of a growth factor called granulocyte-colony stimulating factor (G-CSF), which is a protein that increases the white blood cell count; G-CSF will be continued until the patient's white blood cell count has returned to normal levels.

Patients will remain closely monitored either in the outpatient clinic setting or in the hospital for approximately 2-3 months after the transplant, but possibly longer if there are complications. Follow-up study visits will occur at 6 months and then at 1, 2, 3, 4, and 5 years after the transplant. Study researchers will keep track of the patient's medical condition after leaving the transplant center by phone calls or mailings to patients and their doctors once a year for the rest of the study participants' lives.

Detailed description:
PRIMARY OBJECTIVES:

I. To determine the safety and potential efficacy of reduced intensity conditioning with fludarabine/cyclophosphamide/low-dose total body irradiation (TBI) and allogeneic hematopoietic cell transplantation (HCT) for the stabilization or regression of disease manifestations of severe systemic sclerosis (SSc).

SECONDARY OBJECTIVES:

I. To determine whether stable allogeneic donor engraftment can be safely established with reduced intensity conditioning followed by matched sibling or unrelated donor bone marrow transplantation in patients with severe SSc.

OUTLINE:

Patients receive fludarabine phosphate intravenously (IV) on days -6, -5, -4, -3 and -2 and Cyclophosphamide IV on days -6, -5, and undergo 2 Gray TBI on day -1. Patients receive human leukocyte antigen (HLA)-matched donor bone marrow transplantation on day 0. Patients then receive cyclophosphamide IV on days +3 and +4, and beginning day +5 they start tacrolimus orally (PO) and enteric coated mycophenolic acid.

After completion of initial study treatment, patients are followed up at 6 months and then annually for 5 years.

Arms: arm 1: Patients receive fludarabine phosphate IV on days -4, -3 and -2, cyclophosphamide IV over 1-2 hours on days -6, -5, 3, and 4, and undergo low-dose TBI on day -1. Patients receive hematopoietic cell transplantation on day 0.
Interventions: intervention 1: fludarabine phosphate intervention 2: Mycophenolic Acid intervention 3: tacrolimus intervention 4: total-body irradiation intervention 5: bone marrow transplantation intervention 6: reduced intensity allogeneic hematopoietic stem cell transplantation intervention 7: quality-of-life assessment intervention 8: laboratory biomarker analysis intervention 9: flow cytometry intervention 10: biopsy
Intervention descriptions: intervention 1: Given IV intervention 2: Given PO intervention 3: Given PO intervention 4: Undergo TBI intervention 5: Undergo transplantation intervention 6: Undergo transplantation intervention 7: Ancillary studies intervention 8: Correlative studies intervention 9: Correlative studies intervention 10: Punch biopsy of skin involved with scleroderma

Protocol documents: