Clinical trial NCT06465147: REACT-01: Reversing Autoimmunity Through Cell Therapy
Official title: REACT-01: Reversing Autoimmunity Through Cell Therapy
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Systemic Lupus Erythematosus
Keywords: CAR T cells
Lupus
Systemic Lupus Erythematosus
SLE
Lead sponsor: Seattle Children's Hospital
Sponsor class: OTHER
First posted: 2024-06-18
Enrollment: 12
Sex: ALL
Minimum age (years): 2
Maximum age (years): 30
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This is a phase 1, open-label, non-randomized study enrolling pediatric and young adult research participants with treatment-refractory Systemic Lupus Erythematosus (SLE), to examine the safety, feasibility, and efficacy of administering T cell products derived from peripheral blood mononuclear cells (PBMC) that have been genetically modified to express CD19 specific chimeric antigen receptor (CAR)

A child or young adult meeting all eligibility criteria and meeting none of the exclusion criteria will have their T cells collected. The T cells will then be bioengineered into a CAR T cell that targets circulating and tissue residing B cells.


Eligibility criteria: Inclusion Criteria:

* Male and female subjects aged between 2-30 years old. The first 3 subjects will be aged ≥ 17. The FDA will review safety data to determine if the age can be lowered first to ≥ 12 then, following the treatment of 3 further subjects aged 12-17, to ≥ 2
* Serologically active Systemic Lupus Erythematosus that is refractory to treatment
* Able to tolerate apheresis or already has an apheresis product available for use in manufacturing.
* ≥ 24 weeks post last Rituximab or related B cell depleting therapy
* ≥ 12 weeks post last Belimumab / Anifrolumab therapy
* ≥ 4 weeks post last calcineurin inhibitor treatment
* For subjects receiving non-calcineurin immunosuppressive therapy, on a stable dose for ≥ 8 weeks before enrollment
* For subjects receiving corticosteroid therapy, on a stable dose for ≥ 2 weeks before enrollment
* Adequate organ function
* Adequate laboratory values
* Subjects of childbearing or child-fathering potential must agree to use highly effective contraception from consent through 12 months following infusion of investigational product on trial
* Subjects must be willing to remain within 1 hour's drive of Seattle Children's Hospital for 4 weeks following CAR T cell infusion.
* Subject and/or legally authorized representative has signed the informed consent form for this study

Exclusion Criteria:

* History or presence of active CNS lupus or other CNS disease
* Kidney dysfunction requiring renal replacement therapy
* Pregnant or breastfeeding
* Insufficient pulmonary reserve including history of COPD, \>10 pack year smoking history or SLE lung disease with hypoxia at rest with oxygen saturation ≤92% on room air
* Unable to tolerate repletion with any formulation of IgG.
* Active or prior malignancy, unless the malignancy was treated and there is no evidence of recurrent disease \<5 years from enrollment.
* Prior solid organ transplantation.
* Presence of an active severe infection
* Presence of any condition that, in the opinion of the investigator, would prohibit the subject from undergoing treatment under this protocol

Primary outcomes:
measure: Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]
timeFrame: 28 days post-infusion
measure: Rate of SCRI-CAR19v3 Manufacturing Success
timeFrame: 28 days
Secondary outcomes:
Other outcomes:
Locations:
city: Seattle
country: United States
facility: Seattle Children's Hospital
state: Washington
Study officials:
affiliation: Seattle Children's Hospital
name: Shaun Jackson, MD
role: STUDY_CHAIR
affiliation: Seattle Children's Hospital
name: Colleen Annesley, MD
role: STUDY_DIRECTOR
affiliation: Seattle Children's Hospital
name: Corinne Summers, MD
role: STUDY_DIRECTOR
References: