Overview
This is a first-in-human, single-arm, open-label study evaluating the safety, tolerability, and preliminary efficacy of ALLO-329 in adults with autoimmune diseases: systemic lupus erythematosus (SLE) with and without renal involvement, idiopathic inflammatory myopathy (IIM), and systemic sclerosis (SSc).The purpose of this trial is to evaluate the safety and tolerability of ALLO-329, an allogeneic anti-CD19, anti-CD70 dual chimeric antigen receptor (CAR) T cell therapy, in adults with autoimmune disorders, provide initial evidence of biological activity and clinical response to the treatment and determine the recommended Phase 2 regimen (RP2R).
Principal investigator
Eligibility criteria
Exclusion Criteria: 1. Participants with active systemic bacterial, fungal, or viral infection requiring systemic treatment or a clinically significant active, opportunistic, chronic or recurrent infection. 2. Any active malignancy within 3 years prior to enrollment, except for adequately treated localized basal cell or squamous cell skin cancer, carcinoma in situ or low risk prostate cancer (Gleason score ≤ 6). 3. Prior treatment with CD19 or CD70 targeted therapy or any prior engineered cell therapy (e.g., CAR T therapy). 4. Clinically significant or unstable or uncontrolled acute or chronic disease (e.g., hypothyroidism and diabetes) not due to SLE/IIM/SSc. 5. Symptomatic cardiac or vascular disease requiring medical intervention within 6 months prior to screening, hemodynamically symptomatic pericardial effusion, or symptomatic electrocardiogram abnormality requiring medical intervention. 6. Child-Pugh Class B or C cirrhosis. 7. Symptomatic airway disease requiring medical intervention, pleural effusion ≥ Grade 2, or history of pulmonary embolism requiring anticoagulant therapy within 6 months of enrollment. 8. Participants known to be refractory to platelet or red blood cell transfusions or who will refuse indicated transfusion support to manage cell counts following treatment. 9. Any form of primary, inherited immunodeficiency. 10. Unwilling to participate in an extended safety monitoring period. 11. For participants with SLE: Active disease involving CNS within the last 6 months or SLE that is drug-induced. For those with lupus nephritis, history of dialysis within 12 months or expected need for renal replacement therapy within the next 12 months, or National Institutes of Health (NIH) chronicity score of 3+ in any of the following domains: glomerular sclerosis, glomerular fibrous crescents, tubular atrophy, and/or interstitial fibrosis. 12. Participants with IIM: A myositis other than IIM classification, non-reversible, unrelated or weakness not amenable to assessment, or dermatomyositis with presence of anti-TIF1 gamma antibody. 13. Participants with SSc: Pulmonary arterial hypertension requiring treatment, rapidly progressive or severe SSc gastrointestinal involvement, or prior scleroderma renal crisis.
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