CAR-T Cells in Systemic B Cell Mediated Autoimmune Disease
Trial statusRecruiting
Trial phasePhase 1, Phase 2
Trial typeInterventional
Biological sexAll
Age18+
SponsorMiltenyi Biomedicine GmbH
About this trial
The investigational product is designed to effectively combat B cells in patients with autoimmune diseases. Autologous T cells enriched with CD4/CD8 are genetically engineered using a lentiviral vector to express chimeric antigen receptors (CARs) that target the CD19 antigen on the cell surface of B cells and their precursors. During treatment, patients undergo leukapheresis, lymophodepleting chemotherapy and administration of the expanded CD19-CAR-transduced T cells.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
Subjects must understand and voluntarily sign an informed consent form including written consent for data protection,
Adults aged ≥ 18 years at time of consent,
Adequate renal (eGFR > 30 ml/min/m2), liver (no Child Pugh C), heart (at worst NYHA III, EF > 30%) and pulmonary (FV and DLCO > 30%) function,
Male subjects unless surgically sterile, must agree to use two acceptable methods for contraception (e.g. spermicide and condom) during the trial and refrain from fathering a child starting from the time of signing the Informed Consent Form (ICF) until 12 months after dosing of the IMP,
Disqualifiers
Clinically suitability for a less burdensome and/or approved therapeutic approach, as judged by the investigator
ANC < 1.000/mm3, ALC < 500/mm3 or hemoglobin < 8g/dl, absolute CD3+ T cell count < 100/μl,
Uncontrolled severe concomitant disease, such as cancer (except basal or squamous cell skin cancer) and diabetes mellitus,
Severely impaired renal (eGFR ≤ 30 ml/min/m2), liver (Child Pugh C), heart (NYHA IV, EF ≤ 30%) and pulmonary (FV and DLCO ≤ 30%) function,
Trial design
Design model
Single group
Treatments tested in this trial
anti-CD19 CAR T cell therapy
DrugSingle-dose
Treatment groups
24 Participants
are divided into 1 treatment groupGroup A: Active doseOther 1 intervention
Trial outcomes
Primary outcomes
1
To assess the safety of anti-CD19 CAR T cell therapy in subjects with active B-driven autoimmune disease (SLE, SSc and DM/PM).
Incidence and grading of severity (graded 0-4) of Cytokine Release Syndrome (CRS) and of CAR T cell-associated neurotoxicity (ICANS) within the first 4 weeks after ATMP administration.
Time frame
up to d 28Secondary outcomes
1
Clinical efficacy SSc
Overall Response Rate (ORR) at week 24 measured by specific disease activity composite indexes, each of them validated for the specific disease: SSc: No progression of interstitial lung disease with worsening of FVC1 (\>10 percentage) or worsening of FVC1 (5-10 percentage) plus increase in respiratory symptoms or worsening of FVC1 (5-10 percentage) plus progression of high-resolution computed tomography changes after 24 weeks.
Time frame
at week 242
Clinical efficacy SLE
Overall Response Rate (ORR) at week 24 measured by specific disease activity composite indexes, each of them validated for the specific disease: SLE: Fulfillment of DORIS remission criteria of SLE at week 24.
Time frame
at week 243
Clinical efficacy DM
Overall Response Rate (ORR) at week 24 measured by specific disease activity composite indexes, each of them validated for the specific disease: DM: 2016 ACR/EULAR moderate or major response.
Time frame
at week 244
Cellular response
* amount of CAR T cells in the peripheral blood (cells/µl) * amount of B cells in the peripheral blood (cells/µl) * expansion of CAR T cells in the patient over time in cells/µl
Time frame
up to week 24Sponsors and contacts
Click on the lead sponsor to view all of their trials.
Source ClinicalTrials.gov