Breakfree-2 CAR-T
- Study IRB#:2000037550
- Last Updated:11/06/2026
The Breakfree-2 Clinical Trial is evaluating the safety and tolerability of an investigational CAR T cell therapy in adults with Autoimmune Neurological Disease:
- Relapsing forms of multiple sclerosis (RMS), including RRMS* and active SPMS*, or
- Progressive forms of multiple sclerosis (PMS), including PPMS* and inactive SPMS, or
- Refractory myasthenia gravis (MG)
Pre-study treatment period: At screening, certain tests and procedures may be done to make sure you are eligible to participate in the study. To partake in the study, you will need to stop receiving your current treatment(s) the study doctor will go over this process with you in detail. In preparation for the investigational therapy, you will complete a procedure called leukapheresis. You will be connected to a machine that circulates your blood to collect the T cells that will then be genetically modified at a BMS laboratory before they are returned to your bloodstream at a later time. This procedure may take a few hours.
Study treatment period: Following a single infusion of the investigational therapy, you will remain in the hospital to be monitored for two weeks. After this, you will be asked to remain within a 60-minute drive of your clinical facility for at least an additional 14 days as you will attend clinic visits and undergo procedures such as vital sign measurements, physical exams, blood and urine sample collections, and questionnaires. Before receiving the investigational therapy, you will undergo a treatment known as lymphodepleting (LD) chemotherapy. This is administered to reduce certain white blood cells in the body so that they do not attack the CAR T cells that are introduced during the investigational therapy infusion.
You will be contacted by an experienced CAR T health care provider via phone call every day that you are not in the hospital or visiting the study site until the end of the first four weeks.
Study follow-up period: The study team will check on your health after you have completed the full treatment period and are sent home. These visits will include procedures such as physical exams, blood and urine sample collections, and questionnaires. Some of these visits will be held in person, while others will be over the phone.
Long-term follow-up period: After the study has been completed, you may enter a long-term follow-up if you choose. This will include occasional check-ins to monitor your health after receiving the investigational therapy and will mostly be conducted by phone.
- Age18 years - 60 years
- GenderBoth
Contact Us
For more information about this study, including how to volunteer, contact:
Cynthia Marques
Help Us Discover!
You can help our team find trials you might be eligible for by creating a volunteer profile in MyChart. To get started, create a volunteer profile, or contact helpusdiscover@yale.edu, or call 877-978-8343 for more information.
Study Location
- Yale University
Trial Purpose and Description
We are looking for people 18 to 50 years old with a diagnosis of relapsing multiple sclerosis (RMS), including relapsing-remitting MS (RRMS) and active secondary progressive MS (SPMS), as well as those 18 to 60 with a diagnosis of progressive multiple sclerosis (PMS), including primary progressive MS (PPMS) and/or inactive SPMS, to take part in a clinical research study.
Participants will receive the investigational therapy, study-related medical exams, and study-related laboratory tests at no cost. Reimbursement for travel and other out-of-pocket expenses will be available in addition to possible compensation for time.
To learn more and see if you may qualify, visit BMSStudyConnect.com/MSCARTpatient.
Eligibility Criteria
Inclusion Criteria for Cohort 1:
Relapsing forms of MS (RMS) Participants with RRMS or aSPMS are eligible to be included in the study if all the following criteria apply:
i) Expanded Disability Status Scale (EDSS) ≥ 3.0 and ≤ 5.5
ii) For EU, please refer to the appendix for country-specific inclusion requirements.
iii)Diagnosis of MS according to the 2017 McDonald Criteria (refer to Appendix 6) with a relapsing- remitting course of disease or an initial relapsing-remitting course prior to conversion to aSPMS
iv) Within 12 months prior to Screening and while on treatment with a high-efficacy DMT for at least 6 months (anti-CD20 monoclonal antibody therapy [for US, refer to the appendix for country- specific requirement], cladribine, natalizumab, or alemtuzumab), must have at least one of the following documented:
(1) clinical MS relapse
(2) ≥ 1 gadolinium-enhancing lesion on brain or spinal cord MRI
(3) ≥ 1 new T2 lesion on brain or spinal cord MRI Inclusion
Criteria for Cohort 2:
Progressive forms of MS (PMS) Participants with PPMS or iSPMS are eligible to be included in the study if the following criteria apply:
i) EDSS at screening ≥ 3.0 and ≤ 6.0 PPMS
ii) Diagnosis of PPMS based on 2017 McDonald criteria for diagnosis of multiple sclerosis in patients with a disease course characterized by progression from onset, including:
(1) duration from onset of progressive MS symptoms < 15 years if screening EDSS score > 5.0 OR < 10years if screening EDSS score ≤ 5.0, and
(2) Optional: elevated IgG index and/or OCB (historical or at Screening)
(3) Additionally, PPMS must be treatment-resistant, defined
as:
(a) Participant must have at least 6 months of treatment with ocrelizumab and must have demonstrated an inadequate response to ocrelizumab. For France and Spain, refer to the appendix for country-specific requirements.
(b) EDSS progression of ≥ 1 point for participants with EDSS < 5.5 at Screening or ≥ 0.5 points for participants with EDSS of ≥ 5.5 at Screening in the 2 years prior to study screening, in the absence of clinical activity or Gd+ T1 lesion OR a written narrative reflecting evidence of comparable clinical disability progression in the previous 2 years, based on neurological exams, functional exams, or other participant-reported functional decline (if documented EDSS scores are not available) and confirmed by adjudication.
iSPMS
iii) Diagnosis of MS according to the 2017 McDonald Criteria with an initial relapsing-remitting course prior to conversion to iSPMS documented
as:
(1) EDSS progression of ≥ 1 point for participants with EDSS < 5.5 at Screening or ≥ 0.5 points for participants with EDSS of ≥ 5.5 at Screening in the 2 years prior to study screening, in the absence of clinical activity or Gd+ T1 lesion
OR
(2) A written narrative reflecting evidence of comparable clinical disability progression in the previous 2 years, based on neurological exams, functional exams, or other participant-reported functional decline (if documented EDSS scores are not available) and confirmed by adjudication.
Inclusion Criteria for Cohort 3: Myasthenia Gravis (MG)
i) Documented diagnosis of generalized myasthenia gravis
ii) MGFA classification of II-IV at Screening. For EU, see APPENDIX 12 for country-specific requirements.
iii) Documentation of autoantibodies against AChR or MuSK (historical or at Screening)
iv) Refractory disease defined as disease activity on at least 2 immunosuppressants, including steroids, NSIs, or biologics. For EU, see APPENDIX 12 for country-specific requirements.
v) Has had thymectomy, only if indicated according to current guidelines.
vi) For EU, see APPENDIX 12 for country-specific requirements.
