Status
Conditions
Treatments
About
This phase I/II pilot trial seeks to demonstrate that prolonged administration of Campath-1H without prior marrow or stem cell harvesting can result in immunoablation similar to that achieved by hematopoietic stem cell transplantation (HSCT) from either bone marrow or peripheral blood stem cell sources in children and adolescents with severe treatment refractory systemic sclerosis (SSc).
Full description
Patients, 8 to18 years of age, will be included if they have a proven diagnosis of diffuse cutaneous or systemic SSc as defined by the ACR criteria with evidence of active inflammatory disease Plus at least 1 of the following:SSc-related pulmonary disease with forced vital capacity (FVC) or hemoglobin-adjusted DLCO < 70% and evidence of alveolitis by high-resolution CT scan or bronchoalveolar lavage.
OR:History of SSc-related renal crisis or disease, not active at the time of screening
OR:Moderate to severe upper and/or lower gastrointestinal involvement
AND:Unacceptable toxicity or steroid dependence > 0.3 mg/kg/d,
OR:Failure to respond to, or unacceptable toxicity of MTX > 1mg/kg in combination with cyclosporine or azathioprine or cyclophosphamide 2 kg/d or Rituximab 375 mg/m2 x 4 doses or Imatinib 800 mg/
OR:Disease recurrence after tapering medication above
Sex
Ages
Volunteers
Inclusion and exclusion criteria
4.2 Inclusion/Exclusion criteria 4.2.1 Inclusion criteria
8 to 21 years of age, inclusive
Diffuse, cutaneous dcSSc as defined by the ACR criteria with evidence of active inflammatory disease.
Plus at least 1 of the following:
OR
o History of SSc-related renal crisis or disease, not active at the time of screening
OR
4.2.2 Exclusion Criteria
Pulmonary, cardiac, hepatic, or renal impairment that would limit therapy and compromise survival includes, but is not restricted to, any of the following:
Active gastric antral vascular ectasia (GAVE, "watermelon stomach")
2 mg/kg/day prednisone or equivalent within 30 days of treatment
Unwilling or unable to discontinue DMARDs for treatment of dcSSc
Co-morbid illnesses with an estimated median life expectancy < 5 Years
Active uncontrolled infection
Positive serology for hepatitis B or C, HIV
ANC < 1500 cells/µL, platelets < 120,000 cells/µL, Hct < 27% or Hgb < 9.0 g/dL
Malignancy within the previous 2 years, excluding treated skin cancer
Myelodysplasia
Uncontrolled hypertension
History of hypersensitivity to murine or E. coli proteins
Pregnancy or unwilling to use contraceptive methods for at least 15 months
Steroid dependence: > 2mg/kg/day, prednisone or equivalent within 30 days prior to treatment
History of substance abuse within the last 5 years
History or presence of 2nd autoimmune disease requiring immunosuppressive therapy that has a substantial risk of recurrence
Demonstrated lack of compliance with prior medical care
Lack of rehabilitation potential
4.3 SSc patients, who fulfill the inclusion criteria, will then be assessed for residual thymic function since our previous study of pediatric dcSSc patients demonstrated that the dcSSc patients had decreased thymic function as compared to age matched controls as measured by the proportion of naïve CD4+ T lymphocytes (CD4+, CD31+), recent thymic emigrants (RTE). (5) Patients with less than 40% RTE will be excluded because of concerns about their ability to reconstitute their immune system after immune ablation.
4.4 dcSSc patients, who fulfill the screening criteria, will be consented for entry into the clinical trial.
Loading...
Data sourced from clinicaltrials.gov
Clinical trials
Research sites
Resources
Legal