MB-CART19.1 in Refractory SLE

NCT06189157 | Recruiting Phase 1 DMC

• 1 other identifier: M-2022-398
• Study Type: interventional
• Target: 29
• Locations: 1 country
• Sites: 3

Brief Summary

This is a phase l/ll open-label, multicentre, interventional single-arm trial of MB-CART19.1 in patients with refractory SLE systemic lupus erythematosus. In the phase I part, a maximum of n=12 patients will be treated in a maximum of 3 dose levels. In the phase IIa part, a maximum of n=17 will be treated (n=10 patients in a 1st stage + n=7 patients in a 2nd stage). This includes the patients from the phase I part treated on the recommended dose level.

Conditions

SLE - Systemic Lupus Erythematosus

Outcome Measures

Primary Outcomes (3)

• Phase I: Determination of the recommended dose for phase IIa out of 3 dose levels

  Based on a Bayesian Optimal Interval (BOIN) design with DLT after infusion of MB-CART19.1

  Until day 28 after infusion of MB-CART19.1

• Phase I: Safety and toxicity of MB-CART19.1

  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)

  24 months

• Phase IIa: Proportion of patients in remission after infusion of MB-CART19.1

  Remission is evaluated by fulfillment of DORIS remission criteria of SLE

  Month 6

Secondary Outcomes (8)

• Phase I and Phase IIa: Treatment response to MB-CART19.1

  Day 28, Week 12, Month 6, Month 12, Month 24

• Phase I and Phase IIa: Patient reported outcomes

  Day 0, Day 28, Week 12, Month 6, Month 12, Month 24

• Phase I and Phase IIa: Cellular and humoral immunogenicity

  Day 28, Week 12, Month 6, Month 12

• Phase I and Phase IIa: B cell aplasia and immunoglobulin deficiency

  Day 0, all visits after Day 7 inclusive until Month 24

• Phase I and Phase IIa: Levels of immunology parameters

  Screening, Lymphodepletion, Day 0, Day 14, Day 28, Week 8, Week 12, Month 6, Month 9, Month 12, Month 24

Study Arms (4)

Dose Level 0

EXPERIMENTAL

Phase I: DL 0: 0,1x10e6 MB-CART19.1 cells Dose finding algorithm will start at dose level 1, with dose level 0 as a rescue dose.

Biological: MB-CART19.1

Dose Level 1

EXPERIMENTAL

Phase I: DL 1: 0,5x10e6 MB-CART19.1 cells Patients will be treated in cohorts of 3. If no DLT is determined, the dose can be escalated.

Biological: MB-CART19.1

Dose Level 2

EXPERIMENTAL

Phase I: DL 2: 1,0x10e6 MB-CART19.1 cells At the highest dose level 3 additional patients will be treated.

Biological: MB-CART19.1

Phase II - Recommended dose MB-CART19.1

EXPERIMENTAL

Phase II will evaluate the efficacy and safety in patients treated with the recommended dose

Biological: MB-CART19.1

Interventions

MB-CART19.1 BIOLOGICAL

MB-CART19.1 consists of autologous CD19 Chimeric Antigen Receptor (CAR) transduced CD4/CD8 enriched T cells

Also known as: CD19-targeting CAR T cells, Anti-CD19 CAR T cells

Dose Level 0; Dose Level 1; Dose Level 2; Phase II - Recommended dose MB-CART19.1

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients at least 18 years of age.
• Signed and dated informed consent before the conduct of any trial-specific procedure.
• SLE fulfilling the 2019 ACR/EULAR classification criteria (refer to Appendix 8).
• 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.
• SLE with major organ involvement defined as either:
• Presence of active lupus nephritis according to the following criteria:
• Histology proven class III or IV lupus nephritis according to ISN/RPS 2003 classification
• Urine protein-to-creatinine ratio (UPCR) \>1 in 24-hour urine collection
• Glomerular filtration rate (eGFR) of ≥30 mL/min/1.73 m2
• No history of kidney transplantation.
• Lupus with heart involvement (e.g., myocarditis, pericarditis, endocarditis) as measured by MRI or echocardiography/ultrasound.
• Lupus with pulmonary involvement (Lupus pleuritis, pulmonary arterial hypertension (PAH)) or lung disease defined as:
• Forced Vital Capacity (FVC) ≥ 60 % OR
• Forced Expiratory Volume (FEV1) ≥ 60 %,Total Lung Capacity (TLC) ≥ 60 %, DLCO (diffusion capacity) ≥ 60 % (according to ATS/ERS guidelines).
• Absolute CD3+ T cell count ≥ 100/µl.

You may not qualify if:

• Active clinically significant central nervous system (CNS) dysfunction (including but not limited to uncontrolled seizure disorders, cerebrovascular ischemia or hemorrhage, dementia, paralysis).
• Uncontrolled diabetes mellitus.
• Therapy induced lung disease and tuberculosis.
• Forced Vital Capacity (FVC) \< 60 %, FEV1 \< 60 %, Total Lung Capacity (TLC) \< 60 % and DLCO (diffusion capacity) \< 60 %.
• BILAG A or BILAG B for neuropsychiatric SLE.
• History of a malignancy unless disease free for ≥ 5 years with the exception of basal or squamous cell skin cancer.
• Cardiac function: Unstable coronary heart disease; left ventricular ejection fraction (LVEF) \< 50 %; no active myocarditis.
• Renal function: eGFR \< 30 ml/min/1.73 m2.
• Liver function: Severe hepatic insufficiency defined as a Child-Pugh score \> 10(C) (Appendix 10).
• Known history of infection with human immunodeficiency virus or active infection with hepatitis B (hepatitis B surface antigen positive).
• Known history of infection with hepatitis C virus unless treated and confirmed to be polymerase chain reaction (PCR) negative.
• Any active, uncontrolled bacterial, viral or fungal infection including SARS-CoV-2.
• History of hematopoietic stem cell or solid organ transplantation.
• Irreversible organ damage.
• Medications:

Sponsors & Collaborators

• Miltenyi Biomedicine GmbH: lead

Study Sites (3)

Universitätsklinikum Erlangen, Medizinische Klinik 3

Erlangen, Germany

NOT YET RECRUITING

Otto-von-Guericke-Universität Magdeburg

Magdeburg, Germany

RECRUITING

Universitatsklinikum Tubingen - Medizinische Universitätsklinik Abt. II

Tübingen, Germany

RECRUITING

MeSH Terms

Conditions

Lupus Erythematosus, Systemic

Condition Hierarchy (Ancestors)

Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases

Study Officials

• Georg Schett, Prof. Dr.

  University Clinical Erlangen, Medical Clinic 3

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Clinical Trial Manager

CONTACT

+4922048306820; clinicaltrials.gov@miltenyi.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 22, 2023
• First Posted: January 3, 2024
• Study Start: August 12, 2024
• Primary Completion (Estimated): September 30, 2027
• Study Completion (Estimated): September 30, 2027
• Last Updated: November 26, 2025

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will not share

Locations

DE (3)