Relmacabtagene Autoleucel for the Treatment of Systemic Sclerosis

Liangjing Lu

Status and phase

Enrolling

Phase 1

Conditions

Systemic Sclerosis

Treatments

Biological: Relma-cel

Study type

Interventional

Funder types

Other

Industry

Identifiers

NCT06414135

JWCAR029029

Details and patient eligibility

About

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.

Enrollment

6 estimated patients

Sex

All

Ages

18 to 65 years old

Volunteers

No Healthy Volunteers

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