A Study Evaluating Temferon in Patients With Glioblastoma & Unmethylated MGMT

NCT03866109 | Active Not Recruiting Phase 1 DMC

• 3 other identifiers: TEM-GBM_0012018-001404-112023-510299-29
• Study Type: interventional
• Target: 27
• Locations: 1 country
• Sites: 3

Brief Summary

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

Keywords

Temferon; Gene Therapy; Immunotherapy; Solid tumor

Outcome Measures

Primary Outcomes (1)

• Tolerability and safety of Temferon over the first 90 days following administration as determined by the incidence of adverse events

  Routine clinical and laboratory surveillance

  90 days

Secondary Outcomes (13)

• Long term tolerability and safety of Temferon as determined by the incidence of adverse events

  2 years

• Proportion of patients achieving haematologic recovery by Day +30 (defined as the first of at least 3 consecutive days with a neutrophil count >0.5 x 10^9/L and platelet count >20 x 10^9/L)

  30 days

• Determine the maximum tolerated dose of Temferon

  30 days

• Identify presence of transduced myeloid cells in bone marrow as determined by vector copy number

  Over 2 years

• Incidence of adverse events attributed to the conditioning regimen

  Day +30

Study Arms (1)

Temferon

EXPERIMENTAL

Autologous CD34+-enriched hematopoietic progenitor cells exposed in vitro to specific lentiviral vector encoding for the human interferon-alpha 2 gene. Its expression is tightly controlled by the human TIE2 enhancer/promoter sequence and by a post-transcriptional regulation layer represented by target miRNA sequences. This enables suppression of interferon-alpha2 expression in HSPCs, thereby further increasing the specificity of the delivery strategy for their Tie2 expressing myeloid cell progeny.

Drug: Temferon

Interventions

Temferon DRUG

Genetically modified HSPCs

Temferon

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Genenta Science: lead

Study Sites (3)

Ospedale San Raffaele

Milan, 20132, Italy

Location

Fondazione IRCCS Istituto Neurologico "Carlo Besta"

Milan, 20133, Italy

Location

Policlinico Universitario Fondazione Agostino Gemelli

Rome, Italy

Location

MeSH Terms

Conditions

Glioblastoma

Condition Hierarchy (Ancestors)

Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Study Officials

• Gaetano Finocchiaro, MD

  Ospedale San Raffaele

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: 8 cohorts: Cohorts 1-4, 6: Thiotepa and BCNU Conditioning; Temferon dose 0.5 - 3 x10\^6 CD34+ cells/kg; Cohort 5: Thiotepa and Busulfan Condtioning; Temferon 2 x 10\^6 CD34+ cells/kg; Cohort 7: Busulfan conditioning; Temferon 3 x 10\^6 CD34+ cells/kg; Cohort 8: Busulfan conditioning; Temferon 4 x 10\^6 CD34+ cells/kg;

Study Record Dates

• First Submitted: March 5, 2019
• First Posted: March 7, 2019
• Study Start: March 5, 2019
• Primary Completion (Estimated): June 30, 2026
• Study Completion (Estimated): June 30, 2026
• Last Updated: February 9, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will not share

Locations

IT (3)