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Bone Marrow Transplant

Allogeneic Hematopoietic Cell Transplantation after Nonmyeloablative Conditioning for Patients with Severe Systemic Sclerosis (2067)
Allogeneic Hematopoietic Cell Transplantation after Nonmyeloablative Conditioning for Patients with Severe Systemic Sclerosis
Status Conditions Phase Study ID
Recruiting Autoimmune Diseases
Scleroderma
Systemic Sclerosis
Phase II 2067.00
NCT00622895
Summary

Study Purpose: The major goal of this project is to determine if non-myeloablative stem cell transplantation is an effective treatment for severe systemic sclerosis (SSc). SSc is an autoimmune disease in which a person?s immune system attacks skin and internal organs that leads to scarring and dysfunction. For persons with severe SSc, there exists no effective therapy to halt disease progression, and conventional transplantation is not well tolerated by all SSc patients. Non-myeloablative transplant treatments use lower doses of chemotherapy and radiation than conventional transplant treatments. Study Sites: Participants will receive treatment at the Seattle Cancer Care Alliance (SCCA) and the University of Washington. Study Duration and Follow-up: Participation in the active treatment phase of the study (the transplantation) will last approximately 3 months. Following the transplantation, participants will receive regularly scheduled medical evaluations the first year. Thereafter, participants will have follow-up testing once a year through five years.


Investigator
George Georges, MD
Location    
Seattle Cancer Care Alliance 800-804-8824  
Eligibility Criteria (must meet the following to participate in this study)

 

Ages Eligible for Study:   18 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • HLA-identical sibling or HLA-matched unrelated donor 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 in groups 1-5
  • Group 1: Patients must have 1) both a and b below; and 2) at least one of c, d or e;

    1. diffuse cutaneous scleroderma with skin score of >= 16 (modified Rodnan scale);
    2. duration of systemic sclerosis =< 7 years from the onset of first non-Raynaud's symptom;
    3. presence of interstitial lung disease (FVC or DLCOcorr =<70 % of predicted) and evidence of alveolitis (abnormal bronchoalveolar lavage (BAL) or high resolution chest CT scan) after treatment with intravenous cyclophosphamide >=2 gm given over at least a 3 month period;
    4. left heart failure with LVEF < 50% (that responds to treatment targeted to scleroderma); 2nd or 3rd AV block with other evidence of cardiomyopathy related to SSc; myocardial disease not secondary to SSc must be excluded by a cardiologist;
    5. 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: Progressive pulmonary disease as defined by a decrease in the FVC or DLCO-adjusted by 15 percent or greater of a prior FVC or adjusted diffusion capacity percent of predicted in the previous twelve month period; in addition, patients may have either less skin involvement than group 1 (mRSS < 16) 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 transplant based on the presence of progressive pulmonary disease; this will be defined by a decrease in the FVC or DLCO adjusted since prior autologous transplant of 15 percent or greater of the pre-transplant percent predicted value 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 PI
  • Group 4: Patients who meet group 1 inclusion criteria but may have FVC or DLCO-adjusted< 70% plus have had an adverse event on cyclophosphamide preventing its further use(specifically hemorrhagic cystitis, leukopenia with WBC, 2000 or ANC < 1000 or platelet count < 100,000)
  • 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 DLCO-adjusted less than 45%, patients in all groups must have failed either oral or intravenous cyclophosphamide regimen defined as: IV cyclophosphamide administration for at least > 3 months between first and last cyclophosphamide dose at a total cumulative IV dose of at least 2 grams, oral cyclophosphamide administration for > 4 months regardless of dose, or combination of oral and IV cyclophosphamide for at least > 6 months independent of dose
  • DONOR: HLA genotypically identical sibling or unrelated donor; unrelated donors are required to be matched by standard molecular methods at the intermediate resolution level at HLA-A, B, C and DRB1 and the allele level at DQB1
  • DONOR: Donor must consent to G-CSF administration and leukapheresis
  • DONOR: Donor must have adequate veins for leukapheresis or agree to placement of central venous catheter (femoral, subclavian)

 

Exclusions (conditions that would prevent participation in this study)

Exclusion Criteria:

  • Eligible for SCOT (1948) trial unless patient refuses participation in SCOT secondary to concerns of loss of fertility and other potential toxicities of HDIT
  • Fertile men or women unwilling to use contraceptive techniques during and for 12 months following transplant
  • Evidence of ongoing active infection
  • Pregnancy
  • Patients with a creatinine clearance < 60 ml/min/1.73 m^2 body surface area
  • Uncontrolled clinically significant arrhythmias
  • Clinical evidence of significant CHF (NYHA Class III or IV)
  • LVEF < 40% by echocardiogram
  • Severe pulmonary dysfunction with a hemoglobin corrected DLC0 < 30% or FVC < 45% of predicted or O2 saturation < 92% at rest without supplemental oxygen
  • Significant uncontrolled pulmonary hypertension defined as: Pulmonary artery peak systolic pressure > 55 mmHg by echocardiogram, or pulmonary artery peak systolic pressure 45-55 mmHg by echocardiogram and mean pulmonary artery pressure by right heart catheterization exceeding 25 mmHg at rest (or 30 mmHg with exercise); or New York Heart Association (NYHA)/World Health Organization (WHO, Class III or IV
  • Active hepatitis or liver biopsy evidence of cirrhosis or periportal fibrosis; liver function tests: total bilirubin > 2x the upper limit of normal and/or SGPT and SGPT > 4x the upper limit of normal
  • Patients with poorly controlled hypertension
  • Patients whose life expectancy is severely limited by illness other than autoimmune disease
  • Patients with poorly controlled bleeding from gastric antral vascular ectasia (GAVE) or other GI sites
  • Untreated psychiatric illness, drug/alcohol abuse
  • Inability to give voluntary informed consent
  • Demonstrated lack of compliance with prior medical care
  • Other malignancies except squamous cell or basal cell carcinoma of the skin
  • HIV seropositivity
  • DONOR: Identical twin
  • DONOR: Age less than 12 years
  • DONOR: Current pregnancy
  • DONOR: HIV seropositivity
  • DONOR: Inability to achieve adequate venous access
  • DONOR: Known allergy to G-CSF
  • DONOR: Current serious systemic illness including uncontrolled infections
  • DONOR: Failure to meet institutional criteria for donation as described in the Standard Practice Guidelines
Last Updated
March 26, 2013
See this trial at ClinicalTrials.gov
Access protocol and consent forms at Fred Hutchinson Cancer Research Center
Disclaimer: We update this information regularly. However, what you read today may not be completely up to date.

Please remember:
  • Talk to your health care providers first before making decisions about your health care.
  • Whether you are eligible for a research study depends on many things. There are specific requirements to be in research studies. These requirements are different for each study.