2024-512898-27-00招募中2 期
An open-label phase 1/2 study to evaluate the safety, biological response and efficacy of a single dose of Temferon (autologous CD34+-enriched hematopoietic stem and progenitors cells genetically modified with human Interferon-α2) in patients with metastatic renal cell carcinoma
相关药物
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 12
- 试验地点
- 1
- 主要终点
- To assess tolerability and safety of conditioning and Temferon over a defined period of time following Temferon administration, as evaluated by: - routine clinical and laboratory surveillance; - assessment of autoimmune manifestations; - incidence of adverse events
研究概览
简要总结
The first co-primary objective is to assess, over a defined period of time from the administration of the IMP, the tolerability and safety of both the conditioning regimen and Temferon. The second co-primary objective aims to assess the biological activity of Temferon over a defined period of time following administration.
研究设计
- 分配方式
- Non-randomized
- 主要目的
- Part A (phase 1)
- 盲法
- None
入排标准
- 年龄范围
- 18 years 至 65+ years（18-64 Years, 65+ Years）
- 接受健康志愿者
- 是
入选标准
- •Patient aged between 18 – 70 years old
- •Radiotherapy or metastasectomy of the target lesion are not scheduled within the next four (4) months following Screening
- •Disease progression following approved standard of care treatments for metastatic disease.
- •ECOG PS 0-1 at screening
- •Measurable disease at physical examination or at imaging assessment according to RECIST 1.1 criteria
- •Life expectancy >6 months at screening
- •Patient recovered from all AEs due to previous therapies to ≤Grade 1 or baseline. Participants with ≤Grade 2 neuropathy may be eligible. Participants with endocrine related AEs Grade ≤2 requiring treatment or hormone replacement are eligible
- •Women of childbearing potential must have a negative pregnancy test at screening and agree to use a highly effective method of contraception for the duration of the study.
- •Men with partners of childbearing potential must be willing to use a male condom during the trial and their partner should consider use of a highly effective method of contraception.
- •Adequate cardiac, renal, hepatic, pulmonary, and hematologic function as evidenced by: • LVEF >45% by echo and normal ECG • DLCO >50% and FEV1 and FVC>60% predicted
- •Patient able and willing to provide written informed consent and comply with study protocol and procedures
- •Histologically confirmed diagnosis of unresectable, locally advanced/metastatic RCC with clear cell component, with or without sarcomatoid features
- •Presence of a disease burden sufficiently large to permit biopsy
排除标准
- •Use of investigational agents or procedures in the 4 weeks prior to study enrolment (6 weeks for long-acting agents) or receipt of an experimental gene therapy product in the past 2 years
- •Presence of clinically relevant risk factors that may increase the risk of sepsis in the first 3 months after conditioning
- •Known bleeding diathesis or history of abnormal/severe bleeding or any other known coagulation abnormalities that would contraindication a tissue biopsy, active treatment with anticoagulants.
- •New CNS or rapidly growing metastases or carcinomatous meningitis
- •Presence of more than 3 hepatic metastases or where individual maximum diameter of the hepatic metastasis is ≥5cm.
- •Obesity sufficient to prohibit or to compromise successful percutaneous biopsy of the tumour
- •Previous allogenic bone marrow, renal, liver transplant
- •Prior use of immunosuppressives in the previous 4 weeks prior to enrolment (with the exception of a maximum prednisone equivalent dose of 5mg/day). Corticosteroids must be discontinued prior to entry into the study. Mineralocorticoids and corticosteroids for adrenal replacement therapy are permitted
- •Clinically relevant active viral, bacterial or fungal infection
- •Active autoimmune disease requiring disease modifying treatment, in particular psoriasis, SLE, RA, vasculitis, immune mediated peripheral neuropathies. Use of thyroxine for autoimmune hypothyroidsm is permitted
- •History of sarcoidosis
- •History of current evidence of neuropsychiatric illness including depression, schizophrenia, bipolar disorders, impaired cognitive function, dementia, or suicidal tendency
- •History of severe cardiovascular disease (e.g. NYHA Class III/IV symptoms), prior stroke, CAD requiring intervention or unresolved arrhythmias in the past 6 months, venous thromboembolism or myocardial infarction in the last 6 months, or large artery aneurysm
- •History or evidence of osteonecrosis of the jaw
- •Evidence of haematological neoplasm
- •Positive HIV – 1, HIV- 2, (serology or RNA) and/or hepatitis B (HbsAg) and/or HBV (DNA) and/or HCV RNA and/or Treponema Pallidum or Mycoplasma
- •Active alcohol or substance abuse within 6 months of the study
- •Current pregnancy or lactation
- •Expected to undergo a surgical intervention during the first 3 months of the study
结局指标
主要结局
To assess tolerability and safety of conditioning and Temferon over a defined period of time following Temferon administration, as evaluated by: - routine clinical and laboratory surveillance; - assessment of autoimmune manifestations; - incidence of adverse events
To assess tolerability and safety of conditioning and Temferon over a defined period of time following Temferon administration, as evaluated by: - routine clinical and laboratory surveillance; - assessment of autoimmune manifestations; - incidence of adverse events
To assess the biological activity of Temferon in the tumor of patients with metastatic RCC at a defined period of time following Temferon administration.
To assess the biological activity of Temferon in the tumor of patients with metastatic RCC at a defined period of time following Temferon administration.
次要结局
- Identification of the presence of transduced myeloid cells in bone marrow
- Long term tolerability and safety of Temferon as determined by the incidence of adverse events up to 1 year following Temferon administration according to CTCAE v5.0 criteria
- Incidence, severity and duration of adverse events of special interest as indicated on the study protocol
- Proportion of patients achieving hematological recovery by Day +30
- Identification of the presence of transduced myeloid cells in peripheral blood
- Evaluate persistent transduced myeloid cells in peripheral blood
- Change in functional status (Eastern Cooperative Oncology Group)
- Overall response rate per RECIST version 1.1, at Baseline and at anytime after Temferon infusion, defined as the proportion of patients who achieved a complete or partial response as their best overall response
- Median progression-free survival following Temferon infusion
- Median overall survival following Temferon infusion
- Disease control rate following Temferon infusion
- Time to progression following Temferon infusion
- Primary and / or secondary tumor biopsy and biomarker analyses
研究者
Genenta Science
Scientific
Genenta Science S.p.A.
研究点 (1)
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