A Phase 1 Study Evaluating the Safety and Preliminary Efficacy of ALLO-329, a Dual Anti-CD19/Anti-CD70 Allogeneic CAR T Cell Product in Autoimmune Disease
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 66
- 试验地点
- 17
- 主要终点
- Incidence of Dose Limiting toxicities (DLTs) and Other Safety Parameters
研究概览
简要总结
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).
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 74 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Adults ≥ 18 to < 75 years of age.
- •Adequate hematological function and liver, cardiac, and pulmonary function.
- •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.
- •Signed and dated informed consent form.
- •Willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other procedures.
- •Confirmed active disease (SLE, IIM, or SSc) as defined by the appropriate classification criteria for each respective disease, clinical evidence, and/or laboratory testing.
- •Disease activity as above despite prior treatment with standard of care therapy including at least one immunosuppressive agent for at least 3 months.
排除标准
- •Participants with active systemic bacterial, fungal, or viral infection requiring systemic treatment or a clinically significant active, opportunistic, chronic or recurrent infection.
- •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.
- •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.
- •Clinically significant or unstable or uncontrolled acute or chronic disease (e.g., hypothyroidism and diabetes).
- •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.
- •Child-Pugh Class B or C cirrhosis.
- •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.
- •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.
- •Any form of primary, inherited immunodeficiency.
- •Unwilling to participate in an extended safety monitoring period.
- •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.
- •Participants with IIM: A myositis other than specified classification per exclusion criteria, non-reversible, unrelated or weakness not amenable to assessment, or dermatomyositis with presence of anti-TIF1 gamma antibody.
- •Participants with SSc: Pulmonary arterial hypertension requiring treatment, rapidly progressive or severe SSc gastrointestinal involvement, or prior scleroderma renal crisis.
研究组 & 干预措施
ALLO-329, Cyclophosphamide, Fludarabine
Participants receive ALLO-329 following lymphodepletion regimen comprised of cyclophosphamide and fludarabine.
干预措施: Cyclophosphamide (Drug)
ALLO-329, Cyclophosphamide
Participants receive ALLO-329 following lymphodepletion regimen comprised of cyclophosphamide.
干预措施: ALLO-329 (Genetic)
ALLO-329
Participants receive ALLO-329 without a lymphodepletion regimen.
干预措施: ALLO-329 (Genetic)
ALLO-329, Cyclophosphamide
Participants receive ALLO-329 following lymphodepletion regimen comprised of cyclophosphamide.
干预措施: Cyclophosphamide (Drug)
ALLO-329, Cyclophosphamide, Fludarabine
Participants receive ALLO-329 following lymphodepletion regimen comprised of cyclophosphamide and fludarabine.
干预措施: ALLO-329 (Genetic)
ALLO-329, Cyclophosphamide, Fludarabine
Participants receive ALLO-329 following lymphodepletion regimen comprised of cyclophosphamide and fludarabine.
干预措施: Fludarabine (Drug)
结局指标
主要结局
Incidence of Dose Limiting toxicities (DLTs) and Other Safety Parameters
时间窗: 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)
次要结局
- Disease Response to Treatment - Lupus Nephritis(Up to 60 months)
- 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)
- Disease Response to Treatment - Idiopathic Inflammatory Myopathy(Up to 60 months)
- Disease Response to Treatment - Systemic Lupus Erythematosus(Up to 60 months)
- Disease Response to Treatment - Systemic Sclerosis(Up to 60 months)