Phase II Clinical Trial of Allogeneic Hematopoietic Cell Transplantation After Nonmyeloablative Conditioning for Patients With Severe Systemic Sclerosis
PRIMARY OBJECTIVES:
I. To evaluate the overall effects of allogeneic hematopoietic cell transplantation (HCT) in
systemic sclerosis (SSc).
II. To assess the potential efficacy, in terms of event-free survival (EFS) at 2 (part 1)
and 5 (part 2) years, of allogeneic HCT as treatment for patients with severe SSc.
SECONDARY OBJECTIVES:
I. To evaluate the rate of complications of allogeneic HCT after nonmyeloablative
conditioning including the incidence of graft rejection, regimen-related toxicities, severe
acute and chronic graft-vs-host disease (GVHD), infectious complications, treatment-related
mortality (TRM), and overall survival.
II. To evaluate treatment effects on disease activation/progression, as indicated by
measures of cardiac, pulmonary, gastrointestinal and renal function, as well as skin
thickness, overall functional assessment (SHAQ), use of concomitant disease-modifying
antirheumatic drugs (DMARDs), and occurrence of myositis.
III. To evaluate disease responses after nonmyeloablative conditioning and allogeneic HCT or
immunomodulatory therapy, assessing skin disease by modified Rodnan Skin Score (mRSS),
pulmonary function as measured by diffusing capacity of the lung for carbon monoxide (DLCO)
and forced vital capacity (FVC), Modified Scleroderma Health Assessment Questionnaire
(SHAQ), and Quality of Life using Short Form 36 (SF36).
IV. To evaluate, by mechanistic studies, of the effect of allogeneic HCT on dermal fibrosis
and vasculopathy.
V. To evaluate the late complications of allogeneic HCT after nonmyeloablative conditioning
including the incidence and prevalence of chronic GVHD and time to discontinue
immunosuppression, infectious complications, TRM and overall survival.
VI. To evaluate the treatment effects on disease activation/ progression, as indicated by
measures of cardiac, pulmonary, gastrointestinal and renal function, as well as skin
thickness, overall functional assessment (SHAQ), use of concomitant DMARDs, and occurrence
of myositis.
VII. To evaluate disease responses after nonmyeloablative conditioning and allogeneic HCT or
immunomodulatory therapy, assessing skin disease by modified Rodnan Skin Score (mRSS),
pulmonary function as measured by DLCO and FVC, Modified Scleroderma Health Assessment
Questionnaire (SHAQ), and Quality of Life using Short Form 36 (SF36).
OUTLINE: Patients are assigned to 1 of 2 treatment arms and receive nonmyeloablative
conditioning followed by an allogeneic peripheral blood stem cell transplantation. Treatment
in both arms continues in the absence of disease progression of unacceptable toxicity.
ARM I (transplant): Patients receive fludarabine intravenously (IV) on days -4 to -2.
Patients undergo total-body irradiation on day 0. Patients then undergo peripheral blood
stem cell transplantation on day 0. Patients receive GVHD prophylaxis comprising tacrolimus
orally (PO) twice daily on days -3 to 180 and taper and mycophenolate mofetil PO three times
daily on days 0-28 and then twice daily until day 180 and taper.
ARM II (nontransplant): Patients will receive immunosuppressive therapy based on their
history. The 3 options that they may receive include 1.)mycophenolate mofetil PO twice
daily for 16 months, 2.) Rituximab IV on days 1 and 15 and then repeated at 6 months, and
3.) Cyclophosphamide IV at 28-32 day intervals or orally once daily for 16 months.
After completion of study treatment, patients are followed up periodically for 5 years.
Interventional
Allocation: Non-Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Event-free survival
2 years
No
George Georges
Principal Investigator
Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
United States: Institutional Review Board
2363.00
NCT01047072
Name | Location |
---|---|
Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium | Seattle, Washington 98109 |