relmacabtagene autoleucel for the treatment of systemic sclerosis

Conditions: Systemic Sclerosis

Summary: relma-cel is a product containing cd19-car-transduced t cells. the purpose of this study is to evaluate the safety of relma-cel at different dose levels in patients with early diffuse systemic sclerosis. efficacy will be explored too. if enrolled, participants will undergo leukapheresis, lymphodepleting chemotherapy and administration of relma-cel.


Eligibility criteria:
inclusion criteria: * voluntary to sign the icf * aged between 18-65 years old (inclusive) * diagnosed with diffuse systemic sclerosis according to 2013 acr systemic sclerosis classification criterion * meet the definitions of refractory/progressive as below: 1. refractory: non-respondent to or disease recurrence after remission with conventional therapies. conventional therapies are defined as treated for more than 6 months with low dose steroids (≤ 15 mg prednisone equivalent), cyclophosphamide, antimalarials, azathioprine, mycophenolate mofetil, methotrexate, leflunomide, tacrolimus, cyclosporin or biologics such as rituximab, belimumab, telitacicept, tocilizumab; 2. progressive: having below manifestations within 6 months 1. mrss increases by \>= 3 2. fvc decreases by \> 10% or fvc decreases by \> 5% and dlco decreases by \> 15% * without systemic active infections within 2 weeks of leukapheresis, e.g., infectious pneumonia, tuberculosis * available vascular access for leukapheresis * major organ functions: 1. renal function: crcl ≥50 ml/min (cockcroft/gault equation) 2. bone marrow function: anc ≥ 1000/ul, absolute lymphocyte count ≥100/ul, hb ≥90 g/l, platelet count ≥75 x 10\^9/l. blood transfusion and infusion of growth factors within 7 days of eligibility assessment are not allowed. 3. liver function: alt ≤ 3 x uln, ast ≤ 3 x uln, total bilirubin ≤ 2 x uln (in case of gilbert syndrome, total bilirubin ≤ 3 x uln) 4. coagulation: inr ≤ 1.5 x uln, pt ≤1.5 x uln 5. cardiac function: lvef ≥ 55% * negative result of serum β-hcg measurement for women of childbearing potential at screening and within 48 hours of the first dose of lymphodepletion * female subjects with childbearing potential or male subjects with partners of childbearing potential should adopt medically effective contraception or abstinence from enrollment to 2 years after the end of the study; female subjects with childbearing potential should have a negative serum hcg test within 7 days of enrollment and not in lactation exclusion criteria: * nyha class iv * fvc predicted \< 45% or dlco predicted \< 40% * abnormalities on hrct not attributable to systemic sclerosis * history of autologous stem cell transplantation * with manifestations of renal crisis * with other autoimmune comorbidities that need systemic treatment * with a history of severe drug allergy * with congenital immunoglobulin deficiency * with malignant tumors, except for nonmelanoma skin cancer, in situ cervical cancer, bladder cancer, breast cancer which has been disease free for more than 2 years * with psychiatric diseases or severe cognition dysfunctions * within 5 half-life cycles of the last administration of an investigational product * pregnant, lactation or plan to be pregnant within one year * a history of car-t therapy or other gene-modified t cell targeted therapies * other conditions that are not suitable for enrollment of the study in the judgement of the investigator * the use of any live vaccines against infections within one month of the screening * with any manifestations of active tuberculosis at screening

Keywords: car-t cell therapy systemic sclerosis b cell depletion