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NCT05869955PHASE1Recruiting

A Study of CC-97540, CD-19-Targeted Nex-T CAR T Cells, in Participants With Severe, Refractory Autoimmune Diseases (Breakfree-1)

Juno Therapeutics, Inc., a Bristol-Myers Squibb Company

Start Date

9/13/2023

Completion Date

8/29/2028

Summary

The purpose of this study is to establish the tolerability, preliminary efficacy, and pharmacokinetics of CC-97540 in participants with severe, refractory autoimmune diseases (Breakfree-1).

Eligibility Criteria

Age Range: 18 years to No maximum

Inclusion Criteria \- Diagnosis of Systemic Lupus Erythematosus (SLE) defined as follows:. i) Fulfilling the 2019 European League Against Rheumatism (EULAR) / American College of Rheumatology (ACR) classification criteria of SLE. ii) Presence of anti-dsDNA, anti-histone, anti-chromatin, anti-Ro (anti-SS-A), anti-La (anti-SS-B), or anti-Sm antibodies at screening. \- SLE disease activity:. i) Active disease at screening, with recent ≥ 1 major organ system with a BILAG A score (excluding musculoskeletal, mucocutaneous, and/or constitutional organ system). ii) Inadequate response to glucocorticoids and to at least 2 of the following treatments, used for at least 3 months each: cyclophosphamide, mycophenolic acid or its derivatives, belimumab, azathioprine, anifrolumab, methotrexate, rituximab, obinutuzumab, cyclosporin, tacrolimus or voclosporin. * Diagnosis of Idiopathic Inflammatory Myopathy (IIM) defined as follows:. i) Fulfilling the 2017 EULAR/ACR classification criteria for probable or definite IIM. ii) Participant diagnosed with the following IIM subgroups: dermatomyositis (DM), immune-mediated necrotizing myopathy (IMNM), anti-synthetase syndrome (ASyS), and polymyositis (PM). iii) Presence of at least 1 myositis specific antibody (MSA), associated antibody (MAA), or ANA at screening or prior to screening. * IIM disease activity:. i) Severe/moderate muscle AND/OR skin involvement. ii) Proof of activity as documented by:. A. An active myositis-associated rash OR. B. A recent muscle biopsy OR. C. An elevated CK \> 3 times the upper limit of normal OR. D. Participants diagnosed IIM AND progressive Interstitial Lung Disease (ILD) on high-resolution computed tomography (HRCT) iii) Inadequate response to glucocorticoids and at least 2 of the following treatments used for at least 3 months: azathioprine, methotrexate, cyclosporin A, tacrolimus, MMF, cyclophosphamide, IVIG, JAK inhibitors, and rituximab. * Diagnosis of Systemic Sclerosis (SSc) defined as follows:. i) Fulfilling 2013 EULAR/ACR classification criteria for SSc. ii) Antinuclear Antibody (ANA) positive at screening or prior to screening. \- SSc disease activity:. i) Participants diagnosed with diffuse cutaneous SSc OR diffuse or limited cutaneous SSc AND progressive ILD, AND. ii) Inadequate response to at least 1 of the following treatments used for at least 3 months: mycophenolate, cyclophosphamide, rituximab, nintedanib, azathioprine, tocilizumab, or intravenous immunoglobulins (IVIG). \- Rheumatoid Arthritis (RA) disease activity:. i) Minimum of 3 SJC and 3 TJC on a 66/68 joint count (SJC/TJC). ii) OR participants diagnosed with progressive ILD (interstitial lung disease). iii) AND Inadequate disease response or intolerance to at least one conventional synthetic disease-modifying antirheumatic drug (DMARD) and as well as ≥ 2 DMARDs with different mechanisms of action from the categories biologic disease-modifying antirheumatic drug (bDMARDs) or targeted synthetic disease-modifying anti-rheumatic drug (tsDMARD) for a minimum of 3 months. A. Participants qualifying on progressive ILD may have exhausted the therapies above OR have demonstrated inadequate disease response or intolerance to at least one of the following treatments used for at least 3 months: mycophenolate, tocilizumab, cyclophosphamide, rituximab, azathioprine, nintedinib, pirfenidone. Exclusion Criteria \- Diagnosis of drug-induced SLE rather than idiopathic SLE. \- Other systemic autoimmune diseases (eg, multiple sclerosis, psoriasis, inflammatory bowel disease, etc) are excluded. Participants with type I autoimmune diabetes mellitus, thyroid autoimmune disease, Celiac disease, or secondary Sjögren's syndrome are not excluded. * SLE overlap syndromes including, but not limited to, rheumatoid arthritis, scleroderma, and mixed connective tissue disease, are excluded. * Present or recent clinically significant CNS pathology, within 12 months. * IIM disease activity:. i) Other forms of IIM: Inclusion Body Myositis, Amyopathic DM, any form of juvenile myositis. ii) Myositis other than IIM, eg, drug-induced myositis and PM associated with HIV. iii) Participants with severe muscle damage (Physician VAS for muscle damage in Myositis Damage Index \> 7 cm on a 10 cm scale), permanent weakness due to a non-IIM cause (eg, stroke), or myositis with cardiac involvement. \- SSc disease activity:. i) SSc related PAH requiring active treatment. ii) Rapidly progressive SSc related lower GI (small and large intestines) involvement (requiring parenteral nutrition); active gastric antral vascular ectasia. iii) Prior scleroderma renal crisis. \- RA disease activity:. i) Prior history of or current inflammatory joint disease other than RA. ii) Joint damage and/or deformity that may confound the investigator's ability to accurately assess disease activity. \- Other protocol-defined Inclusion/Exclusion criteria apply.

Interventions

DRUG

CC-97540

DRUG

Fludarabine

DRUG

Cyclophosphamide

DRUG

Tocilizumab

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Conditions

Systemic Lupus ErythematosusIdiopathic Inflammatory MyopathySystemic SclerosisRheumatoid Arthritis

Locations

University of Colorado Anschutz Medical Campus

Aurora, Colorado 80045

United States

Colorado Blood Cancer Institute

Denver, Colorado 80218

United States

Local Institution - 0048

New Haven, Connecticut 06520

United States

Mayo Clinic in Florida

Jacksonville, Florida 32224

United States

University of Miami Hospital and Clinics, Sylvester Cancer Center

Miami, Florida 33136

United States

Local Institution - 0053

Chicago, Illinois 60612

United States

Local Institution - 0030

Baltimore, Maryland 21287

United States

Local Institution - 0038

Boston, Massachusetts 02115

United States

Local Institution - 0046

Boston, Massachusetts 02115

United States

University of Massachusetts Chan Medical School

Worcester, Massachusetts 01655

United States

University of Massachusetts Chan Medical School

Worcester, Massachusetts 01655

United States

University of Michigan

Ann Arbor, Michigan 48109-2800

United States

Henry Ford Medical Center - New Center One

Detroit, Michigan 48202

United States

Mayo Clinic in Rochester, Minnesota

Rochester, Minnesota 55905

United States

Washington University School of Medicine

St Louis, Missouri 63110

United States

Local Institution - 0028

Omaha, Nebraska 68198

United States

Atlantic Health System Overlook Medical Center

Summit, New Jersey 07901

United States

NYU Langone Health

New York, New York 10016

United States

Local Institution - 0054

New York, New York 10021

United States

Icahn School of Medicine at Mount Sinai

New York, New York 10029

United States

Columbia University Irving Medical Center

New York, New York 10032

United States

Local Institution - 0055

New York, New York 10065

United States

The University of North Carolina at Chapel Hill

Chapel Hill, North Carolina 27599

United States

Cleveland Clinic

Cleveland, Ohio 44195

United States

Local Institution - 0027

Columbus, Ohio 43203

United States

UT Southwestern Medical Center

Dallas, Texas 75390

United States

The University of Texas Health Science Center at Houston

Houston, Texas 77030

United States

University of Texas MD Anderson Cancer Center

Houston, Texas 77030

United States

Swedish Medical Center

Seattle, Washington 98104

United States

Local Institution - 0057

Seattle, Washington 98105

United States

Fred Hutchinson Cancer Center

Seattle, Washington 98109

United States

UZ Leuven

Leuven, Vlaams-Brabant 3000

Belgium

Local Institution - 0043

Strasbourg, Alsace 67098

France

CHU Bordeaux Haut-Leveque

Pessac, Aquitaine 33600

France

CHU Montpellier Lapeyronie Hospital

Montpellier, Hérault 34295

France

Hopital Claude Huriez - CHU de Lille

Lille, 59037

France

Local Institution - 0040

Nice, 06202

France

Hôpital Saint-Louis

Paris, 75010

France

Local Institution - 0052

Paris, 75679

France

Centre Hospitalier Universitaire de Rennes - Hôpital Pontchaillou

Rennes, 35033

France

Universitaetsklinikum Wuerzburg

Würzburg, Bavaria 97080

Germany

Universitaetsklinikum Koeln

Cologne, North Rhine-Westphalia 50937

Germany

Universitätsklinikum Leipzig

Leipzig, Saxony 04103

Germany

Universitaetsklinikum Magdeburg

Magdeburg, Saxony-Anhalt 39120

Germany

Charité - Universitaetsmedizin Berlin - Campus Bejnamin Franklin

Berlin, 10117

Germany

Universitaetsklinikum Duesseldorf

Düsseldorf, 40225

Germany

Universitaetsklinikum Erlangen

Erlangen, 91054

Germany

Fondazione Policlinico Universitario Agostino Gemelli IRCCS - Università Cattolica del Sacro Cuore

Rome, Lazio 00168

Italy

Humanitas

Rozzano, Milano 20089

Italy

Hospital Universitari Vall d'Hebron

Barcelona, Barcelona [Barcelona] 08035

Spain

Hospital Universitario Marqués de Valdecilla

Santander, Cantabria 39008

Spain

Hospital Clínic de Barcelona

Barcelona, Catalunya [Cataluña] 08036

Spain

Hospital Universitario Reina Sofia

Córdoba, 14004

Spain

H.R.U Málaga - Hospital General

Málaga, 29011

Spain