Phase I Protocol of Adoptive Immunotherapy With Enriched and Expanded Autologous Natural Killer (NK) Cells for Patients With Ph+ Acute Lymphoblastic Leukemia (ALL) in Complete Hematologic Remission (CHR) But With Persistent/Recurrent Minimal Residual Disease (MRD) ≥60 Years or Not Eligible for Other Post-CHR Treatment Modalities
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 6
- 试验地点
- 6
- 主要终点
- To determine the MTD and the recommended final dose (RD) to be used for further investigations.
研究概览
简要总结
The present study aims at studying how safe and tolerable a new therapy for patients with Acute Lymphoblastic Leukemia (ALL) is.
This new therapy consists of an immunotherapy, that is an approach focusing on the immune system, and it targets ALL patients in complete remission but who may still have the disease at a cellular level (this is called 'minimal residual disease').
For any further information, please, discuss with your treating physician.
详细描述
This is an open label, multicenter, phase I study of adoptive immunotherapy with enriched and expanded autologous natural killer (NK) cells for patients with Ph+ acute lymphoblastic leukemia (ALL) in complete hematologic remission (CHR) but with persistent/recurrent minimal residual disease (MRD) ≥60 years or not eligible for other post-CHR treatment modalities.
The study will investigate the safety and tolerability of a new type of NK-based immunotherapy based on the infusion of escalating doses of ex-vivo expanded autologous NK cells in Ph+ ALL patients. A maximum of 6 patients will be enrolled in two different steps. No conditioning therapies will be administered before the infusion of the expanded NK cells. Patients may receive tyrosine kinase inhibitor (TKI) maintenance.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 60 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Adult subjects with Ph+ ALL in CHR (1st or 2nd) with MRD positivity confirmed at baseline, older or equal to 60 years or not eligible for other post-CHR treatment modalities.
- •WHO score 0-
- •Hematopoietic, liver and renal normal functions defined as follows:
- •WBC bigger or equal to 2.000/mm3 lymphocytes bigger or equal to 500/mm3 neutrophils bigger or equal to 1.000/mm3 platelets bigger or equal to 50.000/mm3 Hb bigger or equal to 9 g/dl creatinine fewer or equal to 1.5 x ULN bilirubin fewer or equal to 1.5 x ULN AST and ALT less than 3 times the upper limit of normal. LDH less than 2 times the upper limit of normal.
- •For male and female subjects of childbearing potential, agreement to use effective contraception.
- •Authorization by Istituto Superiore di Sanità (ISS) according to DM 2 March
- •Signed written informed consent according to ICH/EU/GCP and national local regulations.
排除标准
- •Concurrent chemotherapy or immunotherapy (TKI maintenance is permitted).
- •Any contraindications to perform a leukapheretic procedure for mononuclear cell collection.
- •Active or chronic infection, including Treponema, HIV, HBV and/or HCV unless antigen/PCR negative.
- •Presence of autoimmune symptoms.
- •Pregnant or lactating females.
- •Simultaneous participation in another clinical trial.
- •Any physical or psychological impediment in a patient that could lead the investigator to suspect his/her poor compliance to the protocol.
研究组 & 干预措施
Autologous NK Cells infusions
干预措施: Autologous NK cells infusions (Other)
结局指标
主要结局
To determine the MTD and the recommended final dose (RD) to be used for further investigations.
时间窗: One year from start of treatment.
次要结局
- Number of patients who respond to treatment.(One year from treatment start.)
- Number of adverse events.(Two years from start of treatment.)
- Number of patients able to complete the study.(One year from start of treatment.)
- Time to complete enrolment.(Three years from first patient enrollment.)
- Number and characteristics of immunologic modifications.(One year from start of treatment.)
- Number of patients alive after treatment conclusion.(Two years from treatment start.)
- Number of patients alive without progression.(One year from treatment start.)