A Phase 1 Open-Label Dose-Escalation and Expansion Study to Assess the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Preliminary Efficacy of ALA-101, Allogeneic, Off-the-shelf, CD19-directed CAR-iNKT Cells in Patients With CD19+ Non-Hodgkin Lymphoma and Leukemia
试验速览
- 阶段
- 1 期
- 状态
- 尚未招募
- 发起方
- 入组人数
- 46
- 试验地点
- 5
- 主要终点
- To evaluate the safety and tolerability of ALA-101 in adult participants with CD19+ NonHodgkin Lymphoma (NHL) and CD19+ leukemia
研究概览
简要总结
Phase 1 Open-Label Dose-Escalation and Expansion Study to Assess the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Preliminary Efficacy of ALA-101
详细描述
This is a Phase 1, open-label, dose-escalation and expansion study evaluating the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD), immunogenicity, and preliminary efficacy of ALA-101, an allogeneic, off-the-shelf CD19-directed CAR-iNKT cell therapy, in patients with CD19-positive non-Hodgkin lymphoma (NHL), chronic lymphocytic leukemia (CLL), and hairy cell leukemia (HCL).
The dose-escalation phase will assess safety and determine the maximum tolerated dose (MTD). The dose-expansion/backfill phase will further evaluate safety and preliminary efficacy and establish the recommended Phase 2 dose (RP2D).
Study participation includes screening, lymphodepletion, treatment, and follow-up periods. An end-of-study visit will occur at Month 24, after which participants will enter a long-term follow-up study.
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 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Over 18 years old
- •Confirmed Diagnoses of Confirmed diagnosis of CD19+ non-Hodgkins lymphoma, Diffuse Large B Cell Lymphoma, Follicular Lymphoma, Marginal Zone Lymphoma, Chronic Lymphatic Leukemia or Hairy Cell Leukemia
- •Life Expectancy greater than 3 months
- •Adequate Hepatic and Renal Function
- •Adequate Bone Marrow Function
- •Adequate ECG Vales
- •Agree to use appropriate contraception to avoid becoming pregnant for up to 12 months post treatment and agree not to donate sperm or ova for 12 months post treatment
排除标准
- •Prior anti-CD1d monoclonal antibody treatment
- •Prior allogeneic stem cell transplant except where the participant is greater than 100 days and does not have Graft Versus Host Disease (uncontrolled)
- •Prior Organ Transplant
- •Previous Malignancy in last 3 years that's active or been treated.
- •Current central nervous system involvement by lymphoma or leukaemia
- •Evidence of Cardiac Dysfunction
- •Active Autoimmune disease requiring systemic immunosuppressive therapy within the past 6 months.
- •Known active hepatitis B, hepatitis C or human immunodeficiency virus (HIV) infection.
- •History of Graft Vs Host Disease Grade 2 to 4
- •No active Graft Vs Host Disease following a minimum of 3 months withdrawal from all Graft Vs Host Disease treatments
- •Must not have received systemic anti-cancer therapy for the underlying malignancy within 6 weeks prior to the start of conditioning chemotherapy on Day -
- •Participants that have received autologous or allogenic CAR-T cell therapy within 3 months prior to commencing screening.
- •Use of systemic corticosteroids within 15 days of commencement of conditioning chemotherapy on Day -6 or other immunosuppressive drugs within 30 days
- •Recent major surgery (within 4 weeks prior to commencement of conditioning chemotherapy on Day -6) or planned major surgery within 8 weeks following ALA-101 infusion on Day
- •Active infection requiring intravenous antibiotic, antifungal, or antiviral medication or hospital admission within 10 days prior to commencement of conditioning chemotherapy on Day -6
- •Severe (e.g., severe chronic obstructive pulmonary disease, severe Parkinson's disease) or poorly controlled (e.g., hypertension, diabetes, active inflammatory bowel disease) medical condition.
- •Vaccinated with a live vaccine within 28 days prior to commencement of conditioning chemotherapy on Day -6 or planned live vaccination within 6 months following ALA-101 infusion.
- •Additional criteria apply.
研究组 & 干预措施
Treatment Dose Level -1
Dose level -1: 20 × 10^6 CAR+ iNKT cells (in case of DLTs on Dose Level 1)
干预措施: ALA-101 (Drug)
Treatment Dose Level 1
50 × 10^6 CAR+ iNKT cells (starting dose level)
干预措施: ALA-101 (Drug)
Treatment Dose Level 3
300 × 10^6 CAR+ iNKT cells
干预措施: ALA-101 (Drug)
Treatment Dose Level 2
150 × 10^6 CAR+ iNKT cells
干预措施: ALA-101 (Drug)
Treatment Dose Level 4
500 × 10^6 CAR+ iNKT cells
干预措施: ALA-101 (Drug)
结局指标
主要结局
To evaluate the safety and tolerability of ALA-101 in adult participants with CD19+ NonHodgkin Lymphoma (NHL) and CD19+ leukemia
时间窗: 2 years
Incidence, type and severity of treatment emergent and treatment-related adverse events (AEs) and Incidence and nature of dose-limiting toxicities (DLTs)
次要结局
- To determine the maximum tolerated dose (MTD) and appropriate recommended Phase 2 dose (RP2D) for progression into next stages of clinical studies in adult participants with CD19+ NHL and/or CD19+ leukemia.(2 years)
- To evaluate the preliminary efficacy of ALA-101 in adult participants with CD19+ NHL and/or CD19+ leukemia(2 years)
- To characterize the PK profile of ALA-101(1 year)
- To evaluate the immunogenicity of ALA-101(2 years)
- To characterize the PK profile of ALA-101(1 Year)