A Phase I/IIa Dose Escalation Study Evaluating the Safety and Efficacy of Autologous CD34+-enriched HSPCs Genetically Modified with Human Interferon-α2 in Patients with Glioblastoma Multiforme and Unmethylated MGMT Gene Promoter
This is a non-randomized, open label, phase I/IIa, dose-escalation study, involving a single injection of Temferon, an investigational advanced therapy consisting of autologous CD34+-enriched hematopoietic stem and progenitor cells exposed to transduction with a lentiviral vector driving myeloid specific interferon-alpha2 expression, which will be administered to up to 27 patients affected by GBM who have an unmethylated MGMT promoter. Part A will evaluate the safety and tolerability of 5 escalating doses of Temferon and 3 different conditioning regimens in up to 27 patients, following first line treatment.
• Histologically confirmed, newly diagnosed supratentorial glioblastoma with unmethylated MGMT gene promoter.
• Patients have undergone complete or partial tumor resection.
• Able and willing to provide written informed consent and comply with the study protocol and procedures.
• Eligible for radiotherapy.
• Life expectancy of 6 months or more at Screening.
• Women of child-bearing potential enrolled in the study must have a negative pregnancy test at screening and agree to use acceptable methods of contraception during the trial.
• Men enrolled in the study with partners who are women of child-bearing potential, must be willing to use an acceptable barrier contraceptive method during the trial or have undergone successful vasectomy at least 6 months prior to entry into the study. Successful vasectomy needs to have been confirmed by semen analysis.
• Karnofsky performance score (KPS)≥70.
⁃ Additional inclusion criteria to be assessed within 20 days of Temferon administration:
• Adequate cardiac, renal, hepatic and pulmonary function as evidenced by:
• Left ventricular ejection fraction (LVEF) ≥ 45% by echo and normal electrocardiogram (ECG) or presence of abnormalities not significant for cardiac disease.
• Absence of severe pulmonary hypertension;
• Diffusing capacity of the lung for carbon monoxide (DLCO) \>50% and forced expiratory volume in 1 sec (FEV1) and forced expiratory vital capacity (FVC) \> 60% predicted (if non cooperative: pulse oximetry \> 95% in room air);
• Serum creatinine \< 2x upper limit normal and estimated glomerular filtration rate (eGFR) ≥ 30ml/min/1.73m\^2;
• Alkaline phosphatase (ALP), alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) ≤ 2.5 x upper limit of normal (ULN), and total bilirubin ≤ 2.0 mg/dl.
• Hemoglobin ≥10 g/dL, platelet count ≥100000/mm\^3, absolute neutrophil count \>1500/mm\^3.