Evaluating Temferon for Glioblastoma with Unmethylated MGMT

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 study is testing a new treatment called Temferon to see if it can help people with newly diagnosed glioblastoma who have a specific genetic marker feel better after their standard treatment.

Quick facts

• Phase: Phase1; Phase2
• Study type: Interventional
• Enrollment: 27 (estimated)
• Ages: 18 Years to 70 Years
• Sex: All
• Sponsor: Genenta Science (Industry-sponsored)
• Drugs / interventions: chemotherapy, immunotherapy
• Locations: 3 sites (Milan and 2 other locations)
• Trial ID: NCT03866109 on ClinicalTrials.gov

What this trial studies

This clinical trial is a non-randomized, open-label, phase I/IIa study that investigates the safety and efficacy of Temferon, an investigational therapy using autologous CD34+-enriched hematopoietic stem and progenitor cells modified to express interferon-alpha2, in patients with newly diagnosed glioblastoma multiforme and unmethylated MGMT promoter. The study will involve a dose-escalation approach with up to 27 participants, who will receive a single injection of Temferon following standard treatment. Patients will be monitored for safety and hematological recovery after administration, with follow-up extending up to two years.

Who should consider this trial

Good fit: Ideal candidates are patients with newly diagnosed supratentorial glioblastoma who have undergone tumor resection and have an unmethylated MGMT promoter.

Not a fit: Patients with glioblastoma who have a methylated MGMT promoter or those who are not eligible for radiotherapy may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could provide a novel therapeutic option for patients with glioblastoma, potentially improving survival outcomes.

How similar studies have performed: While this approach is innovative, similar studies using gene therapy and immunotherapy in glioblastoma have shown promise, indicating potential for success.

Eligibility criteria

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.

Where this trial is running

Milan and 2 other locations

• Ospedale San Raffaele — Milan, Italy (Enrolling_by_invitation)
• Fondazione IRCCS Istituto Neurologico "Carlo Besta" — Milan, Italy (Recruiting)
• Policlinico Universitario Fondazione Agostino Gemelli — Rome, Italy (Not_yet_recruiting)

Study contacts

• Study coordinator: Carlo Russo, MD

Conditions Glioblastoma Multiforme; Temferon; Gene Therapy; Immunotherapy; Solid tumor