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

A Phase 1, Multicenter, Open-Label Study Of CC-97540 (BMS-986353), CD19-Targeted Nex-T Chimeric Antigen Receptor (CAR) T Cells, in Participants With Severe, Refractory Autoimmune Diseases: Systemic Lupus Erythematosus, Idiopathic Inflammatory Myopathy, Systemic Sclerosis, or Rheumatoid Arthritis (Breakfree-1)

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).

Study Overview

• Status: Recruiting
• Conditions: Rheumatoid Arthritis; Systemic Lupus Erythematosus; Systemic Sclerosis; Idiopathic Inflammatory Myopathy
• Intervention / Treatment: Drug: Cyclophosphamide; Drug: Fludarabine; Drug: CC-97540; Drug: Tocilizumab

• Study Type: Interventional
• Enrollment (Estimated): 270
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: First line of the email MUST contain NCT # and Site #.
• Study Contact Backup: Name: BMS Clinical Trials Contact Center www.BMSClinicalTrials.com; Phone Number: 855-907-3286; Email: Clinical.Trials@bms.com

Study Locations

• Belgium
  • Vlaams-Brabant
    • Leuven, Vlaams-Brabant, Belgium, 3000
      • Recruiting
      • UZ Leuven
      • Contact: Ellen De Langhe, Site 0019; Phone Number: 003216342542
• France
  • Lille, France, 59037
    • Recruiting
    • Hopital Claude Huriez - CHU de Lille
    • Contact: Ibrahim YAKOUB-AGHA, Site 0016; Phone Number: +33320445551
  • Nice, France, 06202
    • Completed
    • Local Institution - 0040
  • Paris, France, 75010
    • Recruiting
    • Hopital Saint-Louis
    • Contact: Dominique Farge, Site 0018; Phone Number: 33 1 42 49 97 64
  • Paris, France, 75679
    • Withdrawn
    • Local Institution - 0052
  • Rennes, France, 35033
    • Recruiting
    • Centre Hospitalier Universitaire de Rennes - Hôpital Pontchaillou
    • Contact: Roch Houot, Site 0020; Phone Number: 33299289873
  • Alsace
    • Strasbourg, Alsace, France, 67098
      • Withdrawn
      • Local Institution - 0043
  • Aquitaine
    • Pessac, Aquitaine, France, 33600
      • Recruiting
      • CHU Bordeaux Haut-Leveque
      • Contact: Edouard Forcade, Site 0044; Phone Number: +33557656511
  • Hérault
    • Montpellier, Hérault, France, 34295
      • Recruiting
      • CHU Montpellier Lapeyronie Hospital
      • Contact: Jacques Morel, Site 0015; Phone Number: 33467338710
• Germany
  • Berlin, Germany, 10117
    • Recruiting
    • Charité - Universitaetsmedizin Berlin - Campus Bejnamin Franklin
    • Contact: David Simon, Site 0025; Phone Number: +49(0)9131-85-43253
  • Düsseldorf, Germany, 40225
    • Recruiting
    • Universitaetsklinikum Duesseldorf
    • Contact: Joerg Distler, Site 0047; Phone Number: 00492118117817
  • Erlangen, Germany, 91054
    • Recruiting
    • Universitaetsklinikum Erlangen
    • Contact: Georg Schett, Site 0017; Phone Number: 004991318539131
  • Bavaria
    • Würzburg, Bavaria, Germany, 97080
      • Recruiting
      • Universitaetsklinikum Wuerzburg
      • Contact: Marc Schmalzing, Site 0049; Phone Number: +4993120140100
  • North Rhine-Westphalia
    • Cologne, North Rhine-Westphalia, Germany, 50937
      • Recruiting
      • Universitaetsklinikum Koeln
      • Contact: Philipp Koehler, Site 0042; Phone Number: 4922147884774
  • Saxony
    • Leipzig, Saxony, Germany, 04103
      • Recruiting
      • Universitätsklinikum Leipzig
      • Contact: Vladan Vucinic, Site 0041; Phone Number: 493419713841
  • Saxony-Anhalt
    • Magdeburg, Saxony-Anhalt, Germany, 39120
      • Recruiting
      • Universitaetsklinikum Magdeburg
      • Contact: Dimitrios Mougiakakos, Site 0045; Phone Number: 49-391-67-21233
• Italy
  • Lazio
    • Rome, Lazio, Italy, 00168
      • Recruiting
      • Fondazione Policlinico Universitario Agostino Gemelli IRCCS - Università Cattolica del Sacro Cuore
      • Contact: MARIA ANTONIETTA D'AGOSTINO, Site 0012; Phone Number: +393495458711
  • Milano
    • Rozzano, Milano, Italy, 20089
      • Recruiting
      • Humanitas
      • Contact: Armando Santoro, Site 0023; Phone Number: 390282244080
• Spain
  • Córdoba, Spain, 14004
    • Recruiting
    • Hospital Universitario Reina Sofia
    • Contact: ALEJANDRO ESCUDERO, Site 0050; Phone Number: 957011631
  • Málaga, Spain, 29011
    • Recruiting
    • H.R.U Málaga - Hospital General
    • Contact: Antonio Fernandez Nebro, Site 0039; Phone Number: +34951290360
  • Barcelona [Barcelona]
    • Barcelona, Barcelona [Barcelona], Spain, 08035
      • Recruiting
      • Hospital Universitari Vall d'Hebron
      • Contact: JOSEFINA CORTES-HERNANDEZ, Site 0014; Phone Number: 934894171
  • Cantabria
    • Santander, Cantabria, Spain, 39008
      • Recruiting
      • Hospital Universitario Marqués de Valdecilla
      • Contact: Ricardo Blanco, Site 0013; Phone Number: +34 942 20 25 10
  • Catalunya [Cataluña]
    • Barcelona, Catalunya [Cataluña], Spain, 08036
      • Recruiting
      • Hospital Clinic de Barcelona
      • Contact: Ignasi Rodriguez-Pintó, Site 0021; Phone Number: 932275774
• United States
  • Colorado
    • Aurora, Colorado, United States, 80045
      • Recruiting
      • University of Colorado Anschutz Medical Campus
      • Contact: Melissa Griffith, Site 0035; Phone Number: 720-848-7700
    • Denver, Colorado, United States, 80218
      • Recruiting
      • Colorado Blood Cancer Institute
      • Contact: Richard Nash, Site 0024; Phone Number: 303-981-2305
  • Connecticut
    • New Haven, Connecticut, United States, 06520
      • Withdrawn
      • Local Institution - 0048
  • Florida
    • Jacksonville, Florida, United States, 32224
      • Recruiting
      • Mayo Clinic in Florida
      • Contact: Vikas Majithia, Site 0006; Phone Number: 904-953-2000
    • Miami, Florida, United States, 33136
      • Recruiting
      • University of Miami Hospital and Clinics, Sylvester Cancer Center
      • Contact: Lazaros Lekakis, Site 0056; Phone Number: 305-748-0641
  • Illinois
    • Chicago, Illinois, United States, 60612
      • Active, not recruiting
      • Local Institution - 0053
  • Maryland
    • Baltimore, Maryland, United States, 21287
      • Withdrawn
      • Local Institution - 0030
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Not yet recruiting
      • Local Institution - 0038
      • Contact: Site 0038
    • Boston, Massachusetts, United States, 02115
      • Withdrawn
      • Local Institution - 0046
    • Worcester, Massachusetts, United States, 01655
      • Recruiting
      • University of Massachusetts Chan Medical School
      • Contact: Roberto Caricchio, Site 0033; Phone Number: 267-968-7826
    • Worcester, Massachusetts, United States, 01655
      • Not yet recruiting
      • University of Massachusetts Chan Medical School
      • Contact: Jonathan Gerber, Site 0032; Phone Number: 508-635-7093
  • Michigan
    • Ann Arbor, Michigan, United States, 48109-2800
      • Recruiting
      • University of Michigan
      • Contact: Monalisa Ghosh, Site 0031; Phone Number: 734-936-4000
    • Detroit, Michigan, United States, 48202
      • Recruiting
      • Henry Ford Medical Center - New Center One
      • Contact: Alireza Meysami, Site 0037; Phone Number: 313-916-9328
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Recruiting
      • Mayo Clinic in Rochester, Minnesota
      • Contact: Uma Thanarajasingam, Site 0022; Phone Number: 507-422-9855
  • Missouri
    • St Louis, Missouri, United States, 63110
      • Recruiting
      • Washington University School of Medicine
      • Contact: Alfred Kim, Site 0010; Phone Number: 314-326-4785
  • Nebraska
    • Omaha, Nebraska, United States, 68198
      • Completed
      • Local Institution - 0028
  • New Jersey
    • Summit, New Jersey, United States, 07901
      • Recruiting
      • Atlantic Health System Overlook Medical Center
      • Contact: Neil Kramer, Site 0008; Phone Number: 908-598-7940
  • New York
    • New York, New York, United States, 10016
      • Recruiting
      • NYU Langone Health
      • Contact: Amit Saxena, Site 0002; Phone Number: 646-501-7387
    • New York, New York, United States, 10032
      • Recruiting
      • Columbia University Irving Medical Center
      • Contact: Elana Bernstein, Site 0007; Phone Number: 212-305-4308
    • New York, New York, United States, 10029
      • Recruiting
      • Icahn School of Medicine at Mount Sinai
      • Contact: Margrit Wiesendanger, Site 0011; Phone Number: 646-285-7881
    • New York, New York, United States, 10021
      • Withdrawn
      • Local Institution - 0054
    • New York, New York, United States, 10065
      • Withdrawn
      • Local Institution - 0055
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27599
      • Recruiting
      • The University of North Carolina at Chapel Hill
      • Contact: Saira Sheikh, Site 0003; Phone Number: 919-966-0545
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Recruiting
      • Cleveland Clinic
      • Contact: Emily Littlejohn, Site 0005; Phone Number: 216-445-5559
    • Columbus, Ohio, United States, 43203
      • Withdrawn
      • Local Institution - 0027
  • Texas
    • Dallas, Texas, United States, 75390
      • Recruiting
      • UT Southwestern Medical Center
      • Contact: Heidi Jacobe, Site 0036; Phone Number: 214-648-3348
    • Houston, Texas, United States, 77030
      • Recruiting
      • The University of Texas Health Science Center at Houston
      • Contact: Maureen Mayes, Site 0029; Phone Number: 713-500-6905
    • Houston, Texas, United States, 77030
      • Recruiting
      • University of Texas MD Anderson Cancer Center
      • Contact: Chitra Hosing, Site 0034; Phone Number: 713-745-3219
  • Washington
    • Seattle, Washington, United States, 98109
      • Recruiting
      • Fred Hutchinson Cancer Center
      • Contact: Alexandre Hirayama, Site 0058; Phone Number: 206-606-1024
    • Seattle, Washington, United States, 98104
      • Recruiting
      • Swedish Medical Center
      • Contact: Philip Mease, Site 0004; Phone Number: 206-386-2000
    • Seattle, Washington, United States, 98105
      • Not yet recruiting
      • Local Institution - 0057
      • Contact: Site 0057

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Administration of CC-97540	Drug: Cyclophosphamide; Specified dose on specified days; Drug: Fludarabine; Specified dose on specified days; Drug: CC-97540; Specified dose on specified days; Other Names: BMS-986353; Drug: Tocilizumab; Specified dose on specified days

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Number of participants with treatment-emergent adverse events (AEs) in each indication.	Up to 2 years after CC-97540 infusion
Number of participants with serious AEs (SAEs) in each indication.	Up to 2 years after CC-97540 infusion
Number of participants with AEs of special interest (AESI) in each indication.	Up to 2 years after CC-97540 infusion
Number of participants with laboratory abnormalities in each indication.	Up to 2 years after CC-97540 infusion
Number of participants with Dose Limiting Toxicities (DLT) in each indication.	Up to 2 years after CC-97540 infusion
Recommended Phase 2 Dose (RP2D) of CC-97540 in each indication.	Up to 2 years after CC-97540 infusion

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Health Assessment Questionnaire - Disability Index (HAQ-DI)		At week 24
Maximum observed blood concentration (Cmax)		Up to 2 years
Time of maximum observed blood concentration (Tmax)		Up to 2 years
Area under the blood concentration-time curve from time zero to 28 days after dosing (AUC(0-28D))		Up to 2 years
Proportion of participants achieving definition of remission in SLE (DORIS) remission	SLE Cohort	At week 24
Proportion of participants achieving Lupus Low Disease Activity State (LLDAS)	SLE Cohort	At week 24
Change in proteinuria measured by urine protein creatinine ratio (UPCR)	SLE Cohort	At week 24
Proportion of participants achieving Myositis Response Criteria (MRC) Total Improvement Score (TIS) Major Response	IIM Cohort	At Week 24
Change in the Cutaneous Dermatomyositis Disease Area and Severity Index (CDASI)	Only Dermatomyositis (DM) participants in the IIM Cohort	At Week 24
Proportion of participants with ILD with no worsening of pulmonary function including forced expiratory volume (FEV1) (> 10%), forced vital capacity (FVC) (> 10%), and diffusing capacity of the lung for carbon monoxide (DLCO) (> 15%)	IIM Cohort	At Week 24
Proportion of participants achieving a minimal clinically important difference (MCID) of 24% change from baseline of the modified Rodnan Skin Score (mRSS)	SSc Cohort	At Week 24
Participants with an improvement from baseline of the Revised Composite Response Index in Systemic Sclerosis (CRISS)	SSc Cohort	At Week 24
The worsening of pulmonary function including FVC (>10% absolute), DLCO (>15% absolute decline) in participants with interstitial lung disease (ILD)	SSc Cohort	At Week 24
Proportion of participants achieving low Disease Activity Score-28 Joint C-Reactive Protein (DAS28-CRP)	RA cohort	At week 24
Proportion of participants achieving simplified disease activity index (SDAI) remission	RA cohort	At week 24
Proportion of participants with ILD with no worsening of pulmonary function including FVC (> 10%)	RA cohort	At week 24

Collaborators and Investigators

• Sponsor: Juno Therapeutics, Inc., a Bristol-Myers Squibb Company
• Collaborators: Bristol-Myers Squibb Services Unlimited Company
• Investigators: Study Director: Bristol-Myers Squibb, Bristol-Myers Squibb

Publications and helpful links

Helpful Links

• BMS Clinical Trial Information
• BMS Clinical Trial Patient Recruiting

Study record dates

Study Major Dates

• Study Start (Actual): September 13, 2023
• Primary Completion (Estimated): August 29, 2028
• Study Completion (Estimated): August 29, 2028

Study Registration Dates

• First Submitted: May 11, 2023
• First Submitted That Met QC Criteria: May 22, 2023
• First Posted (Actual): May 23, 2023

Study Record Updates

• Last Update Posted (Actual): June 3, 2026
• Last Update Submitted That Met QC Criteria: June 2, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Keywords: CC-97540; BMS-986353
• Additional Relevant MeSH Terms: Musculoskeletal Diseases; Nervous System Diseases; Muscular Diseases; Neuromuscular Diseases; Arthritis; Joint Diseases; Rheumatic Diseases; Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Lupus Erythematosus, Systemic; Scleroderma, Systemic; Arthritis, Rheumatoid; Myositis; Organic Chemicals; Hydrocarbons; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Phosphoramides; Organophosphorus Compounds; Cyclophosphamide; tocilizumab; fludarabine
• Other Study ID Numbers: CA061-1001; 2023-503823-24 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: BMS will provide access to individual anonymized participant data upon request from qualified researchers, and subject to certain criteria. Additional information regarding Bristol Myer Squibb's data sharing policy and process can be found at https://www.bms.com/researchers-and-partners/clinical-trials-and-research.html
• IPD Sharing Time Frame: See Plan Description
• IPD Sharing Access Criteria: See Plan Description
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No