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

• Register: ClinicalTrials.gov
• Last refreshed on: 26 September 2023
• Main ID: NCT01639573
• Date of registration: 18/06/2012
• Prospective Registration: No
• Primary sponsor: Children's Hospital Los Angeles
• Public title: Campath-1h Phase I/II Pilot Trial as Immunoablative Therapy for Refractory Systemic Sclerosis CAMPATH-1H
• Scientific title: Campath-1h as Immunoablative Therapy for Children and Adolescents With Treatment Refractory Systemic Sclerosis
• Date of first enrolment: April 2011
• Target sample size: 0
• Recruitment status: Withdrawn
• URL: https://clinicaltrials.gov/ct2/show/NCT01639573
• Study type: Observational

Countries of recruitment

United States

Contacts

• Name: Katherine Marzan, MD
• Affiliation: Children's Hospital Los Angeles

Key inclusion & 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:

- 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 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

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.



Age minimum: 8 Years
Age maximum: 18 Years
Gender: All

Health Condition(s) or Problem(s) studied

Scleroderma

Intervention(s)

Drug: Campath

Primary Outcome(s)

Primary outcome [Time Frame: 2 years]

Campath [Time Frame: The site will follow patients for 6 months post adverse event.]

Secondary ID(s)

CCI-11-00077

Source(s) of Monetary Support

Please refer to primary and secondary sponsors