Adult patients with refractory active systemic lupus erythematosus (SLE) with organ involvement MedDRA version: 21.1 Level: PT Classification code 10042945 Term: Systemic lupus erythematosus System Organ Class: 10028395 - Musculoskeletal and connective tissue disorders
Conditions
Interventions
Product Name: MB-CART19.1
Product Code: MB-CART19.1
Pharmaceutical Form: Dispersion for infusion
INN or Proposed INN: not available
Current Sponsor code: MB-CART19.1
Other descriptive name: T cells tr
Sponsors
Miltenyi Biomedicine GmbH
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Patients at least 18 years of age 2. Signed and dated informed consent before the conduct of any trial-specific procedure 3. SLE fulfilling the 2019 ACR/EULAR classification criteria (refer to Appendix 8) 4. One BILAG A or two BILAG B despite treatment with at least two of the following treatment options: MMF, cyclophosphamide, rituximab belimumab, anifrolumab, methotrexate, azathioprine 5. SLE with major organ involvement defined as either: a) Presence of active lupus nephritis according to the following criteria: o histology proven class III or IV lupus nephritis according to ISN/RPS 2003 classification; o Urine protein-to-creatinine ratio (UPCR) >1 in 24-hour urine collection; o Glomerular filtration rate (eGFR) of =30 mL/min/1.73 m2 o No history of kidney transplantation. b) Lupus with heart involvement (e.g. myocarditis, pericarditis, endocarditis) as measured by MRI or echocardiography/ultrasound c) Lupus with pulmonary involvement (Lupus pleuritis, pulmonary arterial hypertension (PAH)) or lung disease defined as: o Forced Vital Capacity (FVC) = 60% OR o Forced Expiratory Volume (FEV1) = 60%, Total Lung Capacity (TLC) = 60% and DLCO (diffusion capacity) = 60% 6. Absolute CD3+ T cell count =100/µl; 7. No childbearing potential or negative pregnancy test at screening and before chemotherapy in women with childbearing potential; Subjects must agree to use a contraceptive method from screening until 12 months after the administration of the IMP. 8. Fully vaccinated against SARS-CoV2 according to the recommendations of RKI or confirmed SARS-CoV-2 infection within the last 6 months. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 30 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 30
Exclusion criteria
Exclusion criteria: Criteria for Exclusion Patients will be entered into this trial only if they meet none of the following criteria: 1. Active clinically significant central nervous system (CNS) dysfunction (including but not limited to uncontrolled seizure disorders, cerebrovascular ischemia or hemorrhage, dementia, paralysis); 2. Uncontrolled diabetes mellitus. 3. Therapy induced lung disease and tuberculosis 4. Forced Vital Capacity (FVC) 10 mg within 7 days prior to leukapheresis; • T cell targeting drugs (e.g. mycophenolate mofetil, calcineurin inhibitors) within 21 days prior to leukapheresis, • Prior treatment with anti-CD19 therapy; • Previous adoptive T cell therapy or any gene therapy including CAR T cell therapy; • Live vaccines within 30 days prior to leukapheresis, • Current cytotoxic drugs 16. Hypersensitivity against any drug or its ingredients/impurities that is scheduled or likely to be given during trial participation, e.g. as part of the mandatory preparative chemotherapy or rescue medication/salvage therapies for treatment related toxicities; 17. Contraindication of trial related procedures as judged by the investigator 18. Women of childbearing potential (WOCBP) who do not agree to use highly effective contraceptive measures (Pearl index < 1) or practice true sexual abstinence from any heterosexual intercourse (true abstinence is only acceptable if it is in line with the preferred and usual life style of the participant.) or must have a vasectomised partner as the sole sexual partner (The vasectomised partner must have received medical assessment of the surgical success.) for at least 1 month before the study start, during the study and in the 12 months following the last dose of study treatment. A woman is considered a WOCBP, i.e. fertile, following menarche and until becoming post-menopausal unless permanently sterile. WOCBP who want to become pregnant after completing treatment should seek advice about oocyte cryoconservation prior to treatment because of possible irreversible infertility. WOCBP must refrain from egg donation throughout the study until 12 months after the last dose of study treatment. Highly effective methods of contraception include hormonal contraceptives associated with inhibition of ovulation (oral, intravaginal, transdermal, injectable, implantable) and intrauterine devices or systems (e.g. hormonal and non-hormonal) and bilateral tubal occlusion. Permanent sterilization methods include hysterec
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Primary end point(s): Phase I • Determination of the recommended dose for phase IIa out of 3 dose levels, based on a Bayesian Optimal Interval (BOIN) design, using a target dose limiting toxicity (DLT) rate of 20 %, with DLT until day 28 after infusion of MB-CART19.1 (DLT is defined in section 3.3.2). • Safety and toxicity of MB-CART19.1 per incidence of adverse event (AE), classified according to CTCAE version 5.0, and evaluation and classification of Cytokine Release Syndrome (CRS) and Immune Effector cell-associated Neurotoxicity Syndrome (ICANS). Phase IIa • Proportion of patients in remission at month 6 after infusion of MB-CART19.1. Remission is evaluated by fulfillment of DORIS remission criteria of SLE. ;Timepoint(s) of evaluation of this end point: Phase I: 28 days (recommended dose); from infusion until EoT (AEs/CRS/ICANS) Phase IIa: 6 months;Main Objective: Phase I • To establish the safety and toxicity of MB-CART19.1 and determine the recommended dose for phase IIa (RP2D) Phase IIa • To evaluate the treatment response after infusion of MB-CART19.1 ;Secondary Objective: Phase I and Phase IIa • To evaluate the treatment response, duration of response and relapse after treatment with MB-CART19.1 • To assess the phenotype, expansion and persistence of MB-CART19.1 • Cellular and humoral immunogenicity associated with MB-CART19.1 therapy. • To assess duration of B-cell aplasia and extent of immunoglobulin deficiency • To evaluate the changes in the levels of anti-dsDNA and other SLE associated serum autoantibodies | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Phase I and Phase IIa • Safety and toxicity of MB-CART19.1 per incidence of adverse events (AE), classified according to CTCAE version 5.0; • Treatment response measured by: - Proportion of patients in remission at day 28, week 12, month 6, month 9, month 12 and month 24 measured by DORIS remission criteria of SLE - Proportion of patients with reduction in SLEDAI 2K of = 4 points - Proportion of patients with LLDAS - British Isles Lupus Assessment Group (BILAG) index • Duration of response • Patient reported outcomes: - SF36 - Health Assessment Questionnaire – Disease Index (HAQ-DI) - Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-Fatigue) • Incidence of cellular and humoral immunogenicity after MB-CART19.1 therapy • Immunophenotyping and persistence of circulating immune cells • Percentage of MB-CART19.1 of all T cells as well as total number of MB-CART19.1 in peripheral blood • Cytokine levels in peripheral blood • Occurrence and duration of B cell aplasia, immunoglobulin levels • Levels of serum autoantibodies (Antinuclear Antibodies (ANAs) as anti-dsDNA, anti-nucleosomes, anti-Sm, anti-U1RNP, anti-Ro/SSA, anti-La/SSB, anti-histone, and other SLE specific autoantibodies such as anti-cardiolipin IgG and IgM, anti-C1q, anti-\beta2 glycoprotein IgG and IgM), anti-phosphatidylserine and incidence of sero-conversion • Coagulation and lupus anticoagulant (if positive) • Serum C3 and C4 levels ;Timepoint(s) of evaluation of this end point: Diverse | — |
Countries
Germany
Contacts
Public ContactHead of Global Clinical Research
Miltenyi Biomedicine GmbH
Outcome results
None listed