Low-Dose Conditioning Followed by Donor Stem Cell Transplant in Treating Patients With Severe Systemic Sclerosis
Phase II Clinical Trial of Allogeneic Hematopoietic Cell Transplantation After Nonmyeloablative Conditioning for Patients With Severe Systemic Sclerosis
2 other identifiers
interventional
N/A
1 country
1
Brief Summary
The purpose of the study is to see how well reduced intensity conditioning followed by a stem cell transplant from a donor (allogeneic) works in treating patients with severe systemic sclerosis. In an allogeneic stem cell transplant procedure, stem cells are taken from a healthy donor and transplanted into the patient. Stem cells can be donated by a family member or an unrelated donor who is a complete tissue type match.
Trial Health
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Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
January 11, 2010
CompletedFirst Posted
Study publicly available on registry
January 12, 2010
CompletedPrimary Completion
Last participant's last visit for primary outcome
September 1, 2017
CompletedOctober 31, 2012
October 1, 2012
January 11, 2010
October 29, 2012
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Event-free survival
2 years
Secondary Outcomes (11)
Event-free survival
5 years
Overall survival
2 years
Overall survival
5 years
Time to progression
2 years
Time to progression
5 years
- +6 more secondary outcomes
Study Arms (2)
Arm I (transplant)
EXPERIMENTALPatients receive fludarabine 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 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)
ACTIVE COMPARATORPatients receive mycophenolate mofetil PO twice daily for 16 months, rituximab IV on days 1 and 15 and then repeated at 6 months, and cyclophosphamide IV at 28-32 day intervals or orally once daily for 16 months.
Interventions
Given orally
Given IV
Given orally
Undergo transplantation
Undergo transplantation
Eligibility Criteria
You may qualify if:
- Patients with severe SSc as defined by the American College of Rheumatology and at high-risk for a fatal outcome based on the following prognostic factors from groups 1-5:
- Group 1: Patients with 1) both a. and b. below; and 2) at least one of c., d. or e:
- a. Diffuse cutaneous scleroderma with skin score of \>= 16 (modified Rodnan skin scale)
- b. Duration of systemic sclerosis =\< 5 years from the onset of first non-Raynaud's symptom
- c. Presence of interstitial lung disease with FVC or DLCOcorr =\< 70% of predicted and evidence of alveolitis (abnormal bronchoalveolar lavage \[BAL\] or high resolution chest computed tomography \[CT\] scan)
- d. Left heart failure with left ventricular ejection Fraction (LVEF) \< 50% or pericardial effusion (mild-moderate) or 2nd or 3rd Atrial-Ventricular (AV) block; Myocardial disease not secondary to SSc must be excluded by a cardiologist
- e. History of SSc-related renal disease that is not active at the time of screening; History of scleroderma hypertensive renal crisis is included in this criterion
- Group 2: Patients will have progressive pulmonary disease as the primary indication for transplant as defined by a decrease in the FVC or DLCO by 15 percent or greater in the previous 12-month period. In addition, patients may have either less skin involvement than group 1 (mRSS \< 16) if they have a history of diffuse cutaneous disease and the FVC or DLCOcorr is \< 70% or both FVC and DLCOcorr \>= 70% if they have diffuse cutaneous disease (mRSS \> 16) at screening for the study; Patients must also have evidence of alveolitis as defined by abnormal chest CT or BAL
- Group 3: Have progressive active SSc after prior autologous HCT based on the presence of progressive pulmonary disease; This will be defined by a decrease in the FVC since prior autologous transplant by 10 percent or greater, or DLCO since prior autologous transplant by 15 percent or greater in addition to evidence of alveolitis as defined by chest CT changes or BAL; If patients had prior autologous HCT on the SCOT clinical trial, they must have failed based on the defined study endpoints and be approved by the protocol principal investigator (PI)
- Group 5: Diffuse scleroderma with disease duration =\< 2 years since development of first sign of skin thickening plus modified Rodnan skin score \>= 25 plus ESR \> 25 mm/1st hour and/or Hb \< 11 g/dL not explained by causes other than active scleroderma.
- Unless patients have a DLCOcorr less than 45%, patients must have failed either oral or intravenous cyclophosphamide regimen defined as:
- IV cyclophosphamide administration for \> 6 months or a total cumulative IV dose of 6 g/m\^2, or
- oral cyclophosphamide administration for \> 6 months regardless of dose, or
- combination of oral and IV cyclophosphamide for \> 6 months independent of dose
- Patient must have a sibling who is a) HLA-identical and b) could serve as a donor of a peripheral blood stem cell graft to be placed on the transplant arm or an unrelated donor matched at HLA-A, B, C, DRB1 and DQB1. Patients without an HLA-identical sibling or an HLA-matched unrelated donor that meet the above criteria will be placed on the non-transplant arm
- +6 more criteria
You may not qualify if:
- Eligible for the NIH-sponsored randomized clinical trial (SCOT)
- Fertile men or women unwilling to use contraceptive techniques during and for 12 months or until immunosuppression is discontinued following transplantation
- Evidence of ongoing active infection
- Pregnancy
- Subjects with pulmonary, cardiac, hepatic, or renal impairment that would limit their ability to receive therapy and compromise their survival. This includes but is not restricted to, subjects with any of the following:
- Severe pulmonary dysfunction defined as:
- A hemoglobin corrected DLCOcorr \< 30% or FVC \< 40% of predicted; or
- O2 saturation \< 92% at rest without supplemental oxygen; or
- PO2 \< 70 mmHg or pCO2 \> 50 mmHg without supplemental oxygen
- Significant uncontrolled pulmonary hypertension defined as:
- Pulmonary artery peak systolic pressure \> 45 mmHg by echocardiogram and mean pulmonary artery pressure by right heart catheterization exceeding 32 mmHg at rest or 42 mm Hg during exercise; or
- New York Heart Association (NYHA)/World Health Organization (WHO) classification for pulmonary hypertension, Class III or IV
- Cardiac: Uncontrolled clinically significant arrhythmias; clinical evidence of significant cardiac disease (NYHA Class III or IV); LVEF \< 40% by echocardiogram
- Significant renal pathology, defined as:
- Estimated CrCl \< 60 mL/min (using Cockcroft-Gault formula based on actual body weight) or serum creatinine \> 2.0 mg/dL OR
- +13 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (1)
Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
Seattle, Washington, 98109, United States
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
George Georges
Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
Study Record Dates
First Submitted
January 11, 2010
First Posted
January 12, 2010
Primary Completion
September 1, 2017
Last Updated
October 31, 2012
Record last verified: 2012-10