Idiopathic Inflammatory Myopathy, Systemic Lupus Erythematosus (With and Without Nephritis), Systemic Sclerosis
Conditions
Keywords
Systemic lupus erythematosus, SLE, Lupus nephritis, LN, Idiopathic inflammatory myopathy, IIM, Myositis, Dermatomyositis, Anti-synthetase syndrome, Systemic sclerosis, Scleroderma, SSc, Autoimmune disease, CAR T, Allogeneic CAR T, CD19, CD70, AlloCAR T
Brief summary
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).
Interventions
GENETICALLO-329
An allogeneic CAR T cell therapy targeting CD19 and CD70
DRUGCyclophosphamide
Chemotherapy for lymphodepletion
DRUGFludarabine
Chemotherapy for lymphodepletion
Sponsors
Allogene Therapeutics
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 74 Years
Healthy volunteers
No
Inclusion criteria
1. Adults ≥ 18 to \< 75 years of age. 2. Adequate hematological function and liver, cardiac, and pulmonary function. 3. A highly sensitive urine pregnancy test or serum pregnancy test (for females of childbearing potential) negative at screening. All participants of childbearing potential must be willing to use a highly effective method of contraception for at least 12 months for females (6 months for males) after LD chemotherapy or ALLO-329 administration, whichever is later. 4. Signed and dated informed consent form. 5. Willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other procedures. 6. Confirmed active disease (SLE, IIM, or SSc) as defined by the appropriate classification criteria for each respective disease, clinical evidence, and/or laboratory testing. 7. Disease activity as above despite prior treatment with standard of care therapy including at least one immunosuppressive agent for at least 3 months.
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 5 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) under observation. Prior treatment of cancer with curative intent which in the opinion of the treating oncologist has less than a 10% chance of recurrence in the next 10 years can be allowed after discussion with the sponsor. 3. Prior treatment with CD19 or CD70 targeted therapy or any prior engineered cell therapy (e.g., CAR T therapy), except prior treatment with ALLO-329 in this study. 4. Clinically significant or unstable or uncontrolled acute or chronic disease (e.g., hypothyroidism and diabetes). 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 ALLO-329 dosing. 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: History or 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 prior to signing the informed consent form or expected need for renal replacement therapy within the next 12 months after dosing, 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 specified classification per
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of Dose Limiting toxicities (DLTs) and Other Safety Parameters | Up to 60 months | The incidence of dose limiting toxicities (DLTs) and other safety parameters (including but not limited to treatment emergent adverse events \[AEs\], serious adverse events \[SAEs\], and clinical laboratory abnormalities) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Disease Response to Treatment - Systemic Lupus Erythematosus | Up to 60 months | Efficacy as assessed by rates of achieving SRI-4, LLDAS and DORIS remission. |
| Disease Response to Treatment - Lupus Nephritis | Up to 60 months | Efficacy as assessed by complete renal response (CRR) and partial renal response (PRR). |
| Disease Response to Treatment - Idiopathic Inflammatory Myopathy | Up to 60 months | Efficacy as assessed by ACR/EULAR myositis response criteria components. |
| Disease Response to Treatment - Systemic Sclerosis | Up to 60 months | Efficacy as assessed by change from baseline in the European Scleroderma Trials and Research Group (EUSTAR) activity index. |
| ALLO-329 Peak Expansion (Cmax) | Up to 60 months | — |
| ALLO-329 Persistence Over Time Including Area Under the Expansion Curve (AUC) | Up to 60 months | — |
Countries
Canada, United States
Contacts
CONTACTAllogene Therapeutics, Inc.
STUDY_DIRECTORAllogene Study Director
Allogene Therapeutics, Inc.
Outcome results
None listed