A Phase I Study of BAFF CAR-T Cells (LMY-920) for Treatment of Systemic Lupus Erythematosus
Overview
- Phase
- Phase 1
- Intervention
- LMY-920
- Conditions
- Systemic Lupus Erythematosus
- Sponsor
- Luminary Therapeutics
- Enrollment
- 18
- Locations
- 1
- Primary Endpoint
- Recommended Phase 2 Dose (RP2D)
- Status
- Recruiting
- Last Updated
- 11 months ago
Overview
Brief Summary
This phase 1 study seeks to examine the safety and recommended phase 2 dose (RP2D) of BAFF-ligand CAR-T cells (LMY-920) in adult patients with refractory systemic lupus erythematosus (SLE). It is hypothesized that BAFF CAR-T cells will be safe and will improve SLE disease activity scores.
Detailed Description
This is an open label, phase 1 dose escalation study designed to establish the safety and RP2D of autologous BAFF CAR-T cells in adults with refractory SLE. The planned dose escalation includes 3 dose levels and one de-escalation level. The maximum tolerated dose (MTD) will be determined using a 3+3 dose escalation design. The MTD dose level cohort may be expanded to a total of 6 patients. RP2D may be selected at dose level(s) at or below the MTD based on all data then available (e.g. efficacy, safety, PK and PD), and additional patients enrolled at these levels to expand up to a total of 40 patients in the study, in order to further evaluate safety and efficacy and guide Phase 2 trial design. To ensure patient safety, during dose escalation, treatment of subjects at each dose will be staggered by at least 14 days. For example, the second subject will be enrolled only after the first subject has finished 14 days of safety monitoring from the CAR-T cell infusion, and the third subject will be enrolled only after the second subject has finished 14 days of safety monitoring from the CAR-T cell infusion. In the expansion cohorts, this staggering interval will no longer be required.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Age 18-69 years
- •Confirmed Systemic Lupus Erythematosus (SLE) as per Systemic Lupus International Collaborating Clinics (SLICC) 2012 Criteria with one or more of the following:
- •a. Active disease despite use of standard therapy (i) and one or more additional therapies (ii).
- •i. Corticosteroids (CS), Hydroxychloroquine ii. Mycophenolate mofetil (MMF), Methotrexate (MTX), Azathioprine (AZA), Tacrolimus (TAC), Cyclophosphamide (CYC), Rituximab, and/or belimumab b. Active disease due to intolerance of standard therapy (i) and one or more additional therapies (ii).
- •c. Steroid-Dependent Disease
- •Subjects must meet organ function criteria:
- •Creatinine clearance more than or equal to 30 ml/min calculated by the Cockcroft - Gault formula
- •Subjects must have adequate cardiac function as defined as left ventricular ejection fraction ≥ 40% on the most recent echocardiogram.
- •Adequate pulmonary function with pulse oximetry ≥92% on room air
- •Total Bilirubin ≤ 1.5x the institutional upper limit of normal (except in patients with Gilbert's syndrome)
Exclusion Criteria
- •SLE complicated by:
- •Active neuropsychiatric lupus
- •Active secondary hemophagocytic lymphohistiocytosis (sHLH)
- •Presence of any medical or psychological conditions which may affect patient ability to comply with study protocol requirements and study visits
- •Presence of active, untreated infection such as:
- •Active microbial infection. Patients with possible fungal infections must have had at least 2 weeks of appropriate anti-fungal therapy and be asymptomatic. Patients with active tuberculosis must have had at least 4 weeks of appropriate anti-mycobacterial treatment and be asymptomatic.
- •Active or latent hepatitis B or active hepatitis C (test within 8 weeks of screening), or any uncontrolled infection at screening
- •HIV positive test within 8 weeks of screening
- •Acute/ongoing neurologic toxicity \> Grade 1 except for a history of controlled seizures or fixed neurologic deficits that have been stable/improving over the past 1 months.
- •Patients with concomitant genetic syndrome: such as patients with Fanconi anemia, Kostmann syndrome, Shwachman syndrome or any other known bone marrow failure syndrome. Patients with Down Syndrome will not be excluded.
Arms & Interventions
BAFF CAR T
Autologous BAFF CAR T Therapy
Intervention: LMY-920
Outcomes
Primary Outcomes
Recommended Phase 2 Dose (RP2D)
Time Frame: 5 years
A dose of autologous BAFF CAR-T cells in adults with refractory SLE less than or equal to that at which less than or equal to 1/6 patients experience dose limiting toxicities.
Safety of the Treatment
Time Frame: 5 years
The rate of adverse events graded according to the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 (National Cancer Institute) and rate of dose limiting toxicities after treatment with autologous BAFF CAR-T cells in adults with refractory SLE
Secondary Outcomes
- Efficacy of the Treatment: SELENA-SLEDAI(5 years)
- Efficacy of the Treatment: BILAG(5 years)
- Efficacy of the Treatment: PGA(5 years)