Campath-1h Phase I/II Pilot Trial as Immunoablative Therapy for Refractory Systemic Sclerosis

NCT ID: NCT01639573

Last Updated: 2023-09-13

Basic Information

• Recruitment Status: WITHDRAWN
• Study Classification: OBSERVATIONAL
• Study Start Date: 2011-04-30
• Study Completion Date: 2018-09-02

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

Conditions

Scleroderma

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: PROSPECTIVE

Interventions

Campath

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.

Intervention Type: DRUG

Eligibility Criteria

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)

4.4 dcSSc patients, who fulfill the screening criteria, will be consented for entry into the clinical trial.

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:

• Severe pulmonary dysfunction: hemoglobin-corrected DLCO < 45%, DLCO <4 mL/mmHg/min/L or pO2 < 70 mm Hg or pCO2, ≥ 45 mm Hg without supplemental O2 sat 92% at rest without supplemental O2
• Significant pulmonary hypertension
• Uncontrolled clinically significant arrhythmias
• NYHA heart failure class IV
• LVEF < 50% by echo or prior insertion of a pacemaker or cardioverter-defibrillator
• End-stage renal disease (GFR<50 ml/min/1.73 m2 or creatinine . 2 mg/dl; estimated CrCl < 40 mL/min or active, untreated dcSSc renal crisis at time of enrollment
• Active hepatitis (ALT, AST, or bilirubin > 2x ULN)
• 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

• Minimum Eligible Age: 8 Years
• Maximum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Children's Hospital Los Angeles

OTHER

Sponsor Role: lead

Responsible Party

Diane Brown

Co-Principal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Katherine Marzan, MD

Role: PRINCIPAL_INVESTIGATOR

Children's Hospital Los Angeles

Other Identifiers

CCI-11-00077

Identifier Type: -

Identifier Source: org_study_id