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

Trial ID: NCT03866109

Interventional - Phase 1/2 - Terminated

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.

Conditions

• Glioblastoma Multiforme

Interventions

• Temferon

Eligibility

Inclusion criteria

• 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.

Exclusion criteria

• Use of other investigational agents or procedures within 4 weeks prior to study enrolment (within 6 weeks if use of long-acting agents) or participation in a previous gene therapy study.
• Known hypersensitivity to carmustine (or any other nitrosurea), busulfan, thiotepa, lenograstim, plerixafor, or any excipients used in these products.
• Receipt of any oral or parenteral chemotherapy or immunotherapy within 2 years of Screening.
• Previous allogeneic bone marrow transplantation, kidney or liver transplant.
• Clinical evidence of persistent raised intracranial pressure following surgical resection.
• Clinically relevant active viral, bacterial, or fungal infection at eligibility evaluation.
• Active autoimmune disease or a relevant history of important autoimmune manifestations, in particular psoriasis, systemic lupus erythematosus (SLE), rheumatoid arthritis, vasculitis, immunemediated peripheral neuropathies.
• History of sarcoidosis.
• History or current evidence of neuropsychiatric illness including depression, schizophrenia, bipolar disorders, impaired cognitive function, dementia or suicidal tendency.
• History of severe cardiovascular disease such as prior stroke, coronary artery disease requiring intervention or unresolved arrhythmias in the past 6 months.
• Evidence of any hematological neoplasm.
• Positivity for human immunodeficiency virus type 1 or 2 (HIV-1, HIV-2) (serology or RNA), and/or Hepatitis B Virus Surface Antigen (HbsAg) and/or Hepatitis B Virus (HBV) DNA and/or Hepatitis C virus (HCV) RNA (or negative HCV RNA but on antiviral treatment) and/or Treponema Pallidum or Mycoplasma active infection.
• Active alcohol or substance abuse within 6 months of the study.
• Current pregnancy or lactation.
• Known bleeding diathesis or history of abnormal bleeding, or any other known coagulation abnormalities that would contraindicate lumbar puncture for CSF or future surgery.
• Use of immunosuppressants with the exception of steroids. The maximum permitted dexamethasone (or equivalent) dose is 4 mg per day.

Sponsor

Genenta Science

Source: ClinicalTrials.gov

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