A clinical gene therapy study with hematopoietic stem cells for the treatment, with single dose of Temferon, of patients suffering from metastatic renal cell carcinoma

Prior treatment

• 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
• 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
• Expected to undergo a surgical intervention during the first 3 months of the study
• 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.
• 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

Other illness

• History of current evidence of neuropsychiatric illness including depression, schizophrenia, bipolar disorders, impaired cognitive function, dementia, or suicidal tendency
• 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
• 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

Other

• History or evidence of osteonecrosis of the jaw
• Evidence of haematological neoplasm
• Active alcohol or substance abuse within 6 months of the study
• Current pregnancy or lactation
• Evidence of myelodysplasia or abnormal karyotype on bone marrow biopsy
• Presence of clinically relevant risk factors that may increase the risk of sepsis in the first 3 months after conditioning
• New CNS or rapidly growing metastases or carcinomatous meningitis

• Patient aged between 18 – 70 years old
• Patient able and willing to provide written informed consent and comply with study protocol and procedures
• Histologically confirmed diagnosis of locally advanced/metastatic RCC, with or without sarcomatoid features. Previous nephrectomy or metastasectomy is also allowed.
• 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
• 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