A phase I/II study of CAR-T cells in AutoiMmune disease resistant to B cell Abrogation - CARAMBA

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Universitaetsklinikum Erlangen AöR

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Immune System Diseases [C20]

Trial duration

19 Jan 2026 → ongoing

Decision date (initial)

2025-11-17

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety

To assess the safety of anti-BCMA CAR T (ide-cel) cell therapy in subjects with autoimmune disease resistant to B cell depletion (SLE, IIM, SSc and PSS)

Conditions and MedDRA coding

Progressive systemic autoimmune disease resistant to B cell depletion

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 8

1. Patient must understand and voluntarily sign an informed consent form including written consent for data protection
2. Adults aged ≥ 18 years at time of consent
3. Adequate renal (GFR > 30 ml/min/1.73m2), liver (AST/ALT ≤ 1.5 x ULN, unless deemed to be due to myositis CK-elevation or SLE related hepatitis; no Child Pough C), heart (no NYHA IV, EF ≥ 45 %) and pulmonary (FV and DLCO ≥ 35 %) function
4. Disease specific inclusion criteria for SLE: 1. Diagnosis of SLE defined as follows: a. Fulfilling the 2019 ACR/EURLAR classification criteria of SLE b. Presence of anti-dsDNA, anti-histone, anti-nucleosome, or anti-Sm antibodies at screening or medical history 2. SLE disease activity a. Active disease at screening, defined as ≥ 1 major organ system with a BILAG A score (severe disease activity) or ≥ 2 organ systems with a BILAG B score (moderate activity) b. Insufficient response to, or recurrence of disease, after at least two of the following treatments: cyclophosphamide, mycophenolate mofetil or its derivatives, belimumab, azathioprine, anifrolumab, methotrexate, rituximab, obinutuzumab, hydroxychloroquine, cyclosporin, tracrolimus, voclosporin, IVIG or JAK inhibitors
5. Disease specific inclusion criteria for IIM: 1. Diagnosis of IIM defined as follows: a. Fulfilling the 2017 ACR/EULAR classification criteria for probable or definite DM or PM b. Presence of one or more myositis-specific antibody (aminoacyl tRNA synthetases, Mi2, MDA5, SAE, SRP, ARS, HMGCR, MJ, TIF1gamma) at screening or medical history. Patients must have undergone a sufficient cancer screening prior screening. 2. IIM disease activity a. Presence or signs of active myositis in muscle biopsy or imaging (MRI or PET) and/or signs of interstitial lung disease related to IIM b. In patients with active myositis and muscle weakness as defined by MMT < 142 and 2 of the following criteria: i. VAS patients global ≥ 2 cm ii. VAS physician Global ≥ 2 cm iii. HAQ > 0.25 iv. minimum of one muscle enzyme > 1.3 x ULN v. VAS global extra muscular activity ≥ 2 cm c. Insufficient response to, or recurrence of disease, after at least two of the following treatments: IVIG, methotrexate, azathioprine, cyclophosphamide, tacrolimus, JAK inhibitors, rituximab, mycophenolate mofetil or its derivatives or cyclosporin
6. Disease specific inclusion criteria for SSc: 1. Diagnosis of SSc defined as follows a. Fulfilling the 2013 ACR/EULAR classification criteria of SSc with diffuse skin involvement b. Presence of one or more of the following autoantibodies: Scl-70, anti-RNA polymerase, anti-Th/To, anti-RP11/12 or anti-U3RNP or a tissue biopsy confirming SSc at screening or medical history 2. SSc disease activity a. Signs of fast disease progression including i. disease duration of ≤ 5 years (from onset of first non-Raynaud manifestation) ii. mRSS score ≥ 15 at screening iii. worsening of disease within 6 months defined as mRSS increase ≥ 3 units or involvement of 1 or more new body area(s) or mRSS increase ≥ 2 units in one body area or ≥ 1 tendon friction rub iv. elevated acute phase reactant levels (CRP ≥ 6 mg/L, ESR ≥ 28 mm/h, or platelet count ≥ 330 G/L) b. b. Insufficient response to, or recurrence of disease, after at least two of the following treatments: mycophenolate mofetil or its derivatives, methotrexate, tocilizumab, rituximab, nintedanib, cyclophosphamide or azathioprine and not eligible or denying AHCT
7. Disease specific inclusion criteria for PSS: PSS patients 1. Diagnosis of PSS defined as follows a. Fulfilling the 2016 ACR/EULAR classification criteria of PSS b. Presence of anti-SS-A/Ro and anti-SS-B/La antibodies or a tissue biopsy confirming PSS at screening or medical history 2. PSS disease activity a. Active disease with EULAR Sjögren’s Syndrome Disease Activity Index [ESSDAI] score > 6 b. Serological activity defined as hypocomplementemia or one of the follows: elevated CRP, ESR, IgG or RF c. c. Insufficient response to, or recurrence of disease, after at least two of the following treatments: cyclophosphamide, azathioprine, mycophenolate mofetil or its derivatives, methotrexate, belimumab, rituximab or hydroxychloroquine
8. Patient with insufficient response to, or recurrence of disease, after at least one anti-CD19 / anti-CD20 targeted B cell treatment: rituximab, ocrelizumab, obinutuzumab, CD19 / CD20 T-cell engager or CD19 CAR T-cell therapy

Exclusion criteria 15

1. Clinically suitability for a less burdensome and/or approved therapeutic approach, as judged by the investigator
2. ANC < 1000/mm3, ALC < 200/mm3 or hemoglobin < 8 g/dl, absolute CD3+ T cell count ≥ 100/μl
3. Uncontrolled severe concomitant disease, such as cancer (except basal or squamous cell skin cancer) or severe hepatic insufficiency defined as Child-Pugh score ≥ 10 (C) or unstable coronary artery disease
4. Any condition, including the presence of laboratory abnormalities, which places the subject at unacceptable risk if he/she were to participate in the study or confounds the ability to interpret data from the study
5. Severely Impaired organ function, renal (eGFR < 30 ml/min/m2), liver (AST/ALT > 3 x ULN, Child Pough C), heart (NYHA IV, EF < 40 %) and lungs (FV and DLCO < 30 %)
6. Any concomitant severe active infection (e.g., HIV, hepatitis B or C or active tuberculosis as defined by a positive QuantiFERON TB-test; if presence of latent tuberculosis is established then treatment according to local guidelines must have been initiated prior to enrollment)
7. Pregnant or lactating females
8. Known hypersensitivity to any drug components
9. Malignancy in the last 5 years before screening, except stage 1 prostate cancer, DCIS, skin SCC and BCC
10. Current therapy with cytotoxic drugs
11. Diagnosis of severe neuropsychiatric SLE, inclusion body myositis or limited SSc
12. Requirement for immunization with live vaccine during the study period or within 14 days preceding leukapheresis
13. Participants who are younger than 18 years or participants who are incapable to understand the aim, importance and consequences of the study and to give legal informed consent
14. Have a history of alcohol or substance abuse within the preceding 6 months that, in the opinion of the investigator, may increase the risks associated with study participation or study agent administration, or may interfere with interpretation of results
15. Patients who possibly are dependent on the sponsor, the principal investigator or investigator (e.g., family members)

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Incidence of any grade ≥ 3 CRS or grade ≥ 3 ICANS, any grade ≥ 3 organ toxicity that does not resolve to grade ≤ 2 within 72 hours, any grade ≥ 3 immune effector cell-associated hemophagocytosis, grade ≥ 2 ICANS and CRS that does not resolve to grade 1 within 7 days following adequate therapy

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Universitaetsklinikum Erlangen AöR

Sponsor organisation

Universitaetsklinikum Erlangen AöR

Address

Maximiliansplatz 2, Innenstadt Innenstadt

City

Erlangen

Postcode

91054

Country

Germany

Scientific contact point

Organisation

Universitaetsklinikum Erlangen AöR

Contact name

Klinik für Rheumatologie und Immunologie

Public contact point

Organisation

Universitaetsklinikum Erlangen AöR

Contact name

Klinik für Rheumatologie und Immunologie

Locations

1 EU/EEA country · 1 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 6 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

2 submissions — initial application plus substantial / non-substantial modifications