Relmacabtagene Autoleucel for the Treatment of Systemic Sclerosis

Launched by LIANGJING LU · May 9, 2024

Keywords

ClinConnect Summary

This clinical trial is studying a new treatment called Relmacabtagene Autoleucel (or Relma-cel) for people with early diffuse systemic sclerosis, a serious autoimmune disease that can cause skin and internal organ problems. The main goal of the trial is to assess the safety of Relma-cel at different doses and to see how well it works. To participate, individuals must be between 18 and 65 years old, have been diagnosed with diffuse systemic sclerosis, and have not responded well to standard treatments. Participants will undergo a procedure to collect their immune cells, receive chemotherapy to prepare their body for treatment, and then receive the Relma-cel infusion.

If you're considering joining the trial, it's essential to know that participants should not have serious heart, kidney, or liver issues and should be free of active infections. Women who could become pregnant will need to use effective birth control during the study and for two years afterward. The trial is currently recruiting participants, and those who join can help researchers learn more about this potential new therapy, which could lead to better treatment options for systemic sclerosis in the future.

Gender

ALL

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