Scleroderma
Conditions
Keywords
Patients with Scleroderma
Brief summary
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).
Detailed 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
Interventions
DRUGCampath
Pediatric patients with dcSSc are eligible for the clinical trial if they fulfill the inclusion and exclusion criteria of the trial. The inclusion and exclusion criteria are based upon those of the SCOT trial for adult dcSSc patients, which is the Phase 3 clinical trial in the United States comparing autologous HSCT to monthly high dose cyclophosphamide (CY) alone.
Sponsors
Children's Hospital Los Angeles
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
8 Years to 18 Years
Healthy volunteers
No
Inclusion 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: * dcSSc-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 o 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 * Failure to respond to, or unacceptable toxicity of MTX \> 1mg/kg in combination with cyclosporine or azathioprine or cyclophosphamide or Rituximab 375 mg/m2 x 4 doses or Imatinib 800 mg/d or tocilizumab 8 mg/kg for at least 3 doses. * Disease recurrence after tapering medication above (in #4) 4.2.2
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Primary outcome | 2 years | To determine why the extended administration of Campath-1H results in immune ablation in some patients and immunosuppression in others, Number of Participants with Adverse Events as a Measure of Safety and Tolerability Campath-1H antibody levels during and after the completion of the Campath administration. (47) Thus, both the peak Campath-1H levels as well as the duration of circulating Campath will be determined. |
| Campath | The site will follow patients for 6 months post adverse event. | Number of Participants with Adverse Events as a Measure of Safety and Tolerability |
Outcome results
None listed