The purpose of this study is to assess safety and efficacy of Brentuximab vedotin, a CD30-directed antibody-drug conjugate, in patients with active diffuse cutaneous systemic sclerosis (dcSSc) who relapsed after discontinuation of Brentuximab vedotin.
Worsening mRSS of ≥ 4 points as compared to mRSS score at the end of treatment visit (week 48) in the initial study (BV201708).
Able to give informed consent.
Poor pulmonary function (FVC<40% and/or DLCO<30%).
Pregnancy, breast feeding or child bearing potential without practicing highly effective contraception (and partners for men in the study).
Clinically significant pulmonary hypertension requiring drug therapy.
Clinically significant cardiac disease.
Single group
Brentuximab vedotin
DrugDose 0.6mg/kg will be given every 3 weeks for 16 cycles (48 weeks), in addition to standard of care medications for SSc that may include cyclophosphamide, methotrexate, azathioprine, mycophenolate mofetil (MMF, cellcept) and mycophenolic acid (myfortic)
Change in skin thickness measured by modified Rodnan Skin Score
Skin improvement is defined as the mean mRSS decrease of ≥8 points modified Rodnan Skin Score (mRSS): is a standard outcome measure for skin disease in SSc and calculated by measuring skin thickness in 17 different body sites (each site scored 0-3, with a total possible additive score of 51). A higher skin score (or a higher "skin thickness") and progression of this score, is predictive of internal organ involvement and mortality. While a lower or improving (lessening) score is associated with favorable outcomes, including better survival.
Change in skin thickness over time measured by modified Rodnan Skin Score
modified Rodnan Skin Score (mRSS): is a standard outcome measure for skin disease in SSc and calculated by measuring skin thickness in 17 different body sites (each site scored 0-3, with a total possible additive score of 51). A higher skin score (or a higher "skin thickness") and progression of this score, is predictive of internal organ involvement and mortality. While a lower or improving (lessening) score is associated with favorable outcomes, including better survival.
Change in physician global assessment of disease activity
Measured on a Visual Analogue Scale (VAS) from 0-10, with 0 being no disease activity and 10 being the worst possible disease activity.
Change in physician global assessment of disease severity
Measured on a Visual Analogue Scale (VAS) from 0-10, with 0 being no disease severity and 10 being the worst possible disease severity.
Change in physician global assessment of disease damage
Measured on a Visual Analogue Scale (VAS) from 0-10, with 0 being no disease damage and 10 being the worst possible disease damage.
Regimen-related toxicities
Defined as Adverse Events (AEs) \>= Grade 3 and assessed by the investigator as 1 of the following: related or unrelated to treatment.
Infectious complications
Any infectious complication will be tracked under Adverse Event recording
Change in peripheral levels of T-cell activation marker - sIL-2R
interleukin 2 receptor (sIL-2R) Serum sIL-2R level is a sensitive and quantitative marker of circulating peripheral blood mononuclear cell activation. Normal range of serum sIL-2R is below 2500 pg/ml. High levels may be found in conditions associated with T-cell activation.
Change in peripheral levels of fibrillogenesis - amino terminal propeptide of type III collagen
Changes in serum amino-terminal propeptide of type III collagen levels. Amino-terminal propeptide of procollagen type III (PIIINP) is generated during the synthesis of type III collagen. PIIINP is a non-specific marker of soft tissue injury. PIIINP in serum has been shown to correlate with fibrillogenesis, and thus to be a potential direct marker of type III collagen deposition. PIIINP reference range Adult (\>19 years): 1.2 - 4.2 ug/L and myofibroblast score in skin biopsies (24 and 48 weeks) if the study looks favorable with respect to potential benefit and safety.
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London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph's
Lead sponsor
Seattle Genetics (now a wholly owned subsidiary of Pfizer)
Collaborator
Pfizer
Collaborator
