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Glioblastoma MultiformePhase 1/2TEM-GBMNCT03866109

A Study Evaluating Temferon in Patients With Glioblastoma & Unmethylated MGMT

A Phase 1/2 study testing Temferon in people with Glioblastoma Multiforme, run by Genenta Science at 3 sites in Italy.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial 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… Read more about this study

Who is it for?
Ages 18 to 70 years
Conditions the study is for
Glioblastoma Multiforme
What is being tested?
Temferon
Could I receive a placebo?
No, everyone receives an active treatment
How many people
25 participants
Where
3 sitesItaly
Study dates
5 Mar 2019to 27 May 2026
Phase
Phase 1/2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 70 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.
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  • 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.

Who cannot join

  • 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.
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  • 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.

Trial locations and contacts

3 sites in 1 country.

Italy3 sites
  • Ospedale San Raffaele

    Milan, 20132

  • Fondazione IRCCS Istituto Neurologico "Carlo Besta"

    Milan, 20133

  • Policlinico Universitario Fondazione Agostino Gemelli

    Rome

Other trials in Italy

About this study

Official title: 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.

Read the detailed description

This is a non-randomized, open label, multicenter, phase I/IIa, therapeutic-exploratory, dose escalation, prospective study, involving a single injection of Temferon, an investigational ATMP consisting of autologous CD34+-enriched HSPCs exposed to transduction with a 3rd generation lentiviral vector driving myeloid-specific IFN-alpha2 expression, which will be administered to up to 27 patients affected by GBM who have an unmethylated MGMT promoter. The study will recruit and follow-up patients at a specialist neurosurgical and neuro-oncology units in Italy. Administration of Temferon and hematological follow up will take place at specialist hematology and bone marrow transplantation units.

Potentially eligible patients will be identified immediately after surgical resection of GBM once the MGMT promoter methylator status is known. Once written, informed consent is obtained, and screening procedures have been completed, harvesting of HSPCs will occur. A standard of care regimen lasting approximately 6 weeks, will then take place . During this time, Temferon manufacturing will occur. Following completion of radiotherapy, patients will be admitted for receipt of a conditioning regimen consisting of BCNU and thiotepa (Cohorts 1-6), busulfan and thiotepa (Cohort 5), or busulfan (Cohorts 7 and 8). This will be followed by administration of Temferon. In-patient monitoring will occur until hematological recovery occurs. Thereafter, regular follow-up of patients will occur up to 2 years (+720 days) with the majority of assessments and procedures. At the +720 day visit, patients will be invited to participate in a long term follow-up study which will last for an additional 6 years.

In Part A of the study, 8 cohorts of 3 patients will receive 5 escalating doses of Temferon. On completion of dose escalation in Part A, a conditioning regimen and single dose of Temferon will be selected to be studied in up to a further 6 patients.

In the event that GBM disease progression occurs, patients will be managed with second line therapies including second surgery, TMZ, BCNU, fotemustine or any other approved therapy for GBM.

Being tested
Temferon
Keywords
Temferon, Gene Therapy, Immunotherapy, Solid tumor
Medical subject headings
Glioblastoma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • TemferonDrug

    Genetically modified HSPCs

Study groups in NCT03866109
Study groupRoleWhat they receive
TemferonExperimentalAutologous 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.
Receives: Drug: Temferon

What is being measured

The primary outcome is the main question the study is designed to answer.

  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

    Measured: 90 days

Secondary outcomes (13)
  1. Long term tolerability and safety of Temferon as determined by the incidence of adverse events

    Routine clinical and laboratory surveillance

    Measured: 2 years

  2. 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)

    Hematologic recovery is 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.

    Measured: 30 days

  3. Determine the maximum tolerated dose of Temferon

    Presence of a CTCAE Grade 3-5 adverse event (AE) that occurs within the first 30 days and is attributed to Temferon.

    Measured: 30 days

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

    VCN

    Measured: Over 2 years

  5. Incidence of adverse events attributed to the conditioning regimen

    Adverse events for BCNU and thiotepa, busulfan and thiotepa, or busulfan monotherapy up to Day +45

    Measured: Day +30

  6. Identify presence of transduced myeloid cells in peripheral blood as determined by vector copy number

    VCN

    Measured: Over 2 years

  7. Determine clinical response in patients as determined by iRANO criteria

    iRANO criteria

    Measured: Over 2 years

  8. Determine progression free survival in patients

    MRI

    Measured: Over 2 years

  9. Determine overall survival in patients

    Survival data

    Measured: 2 years

  10. Changes in functional status (Eastern Cooperative Oncology Group)

    ECOG assessment:

    0 Fully active, able to carry on all pre-disease performance without restriction

    1. Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature, e.g., light house work, office work
    2. Ambulatory and capable of all selfcare but unable to carry out any work activities; up and about more than 50% of waking hours
    3. Capable of only limited selfcare; confined to bed or chair more than 50% of waking hours
    4. Completely disabled; cannot carry on any selfcare; totally confined to bed or chair
    5. Dead

    Measured: 2 years

  11. Changes in functional status (Karnofsky)

    Karnofsky assessment

    Measured: 2 years

  12. Changes in Quality of Life (European Organisation for Research and Treatment of Cancer EORTC C30)

    EORTC C30 questionnaire

    Measured: 2 years

  13. Changes in Quality of Life (BN20)

    European Organisation for Research and Treatment of Cancer BN20 questionnaire

    Measured: 2 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted7 Mar 2019
  2. Study start5 Mar 2019
  3. Primary completion27 May 2026
  4. Study completion27 May 2026

Why it stopped: LVLP (pt GBM-01034) took place on 27may2026. The 2 remaining slots allocated by the protocol for the additional cohort to generate safety data prior to study Part B will not be filled. No safety concerns. Benefit-risk profile unchanged.

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Sequential
Model description
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;
Masking
None (open label)
Enrolment
25 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03866109
Sponsor's protocol ID
TEM-GBM_001
Other IDs
2018-001404-11, 2023-510299-29, 2023, 2018
Acronym
TEM-GBM
Status last verified
Jun 2026
First submitted
5 Mar 2019
Last updated
11 Jun 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • Gentner B, Eoli M, Farina F, Barcella M, Capotondo A, Mazzoleni S, Brambilla V, Francavilla A, Garramone M, Carrabba MG, Ferla V, Bruno A, Alvisi G, Coltella N, Montini E, Hadadi L, Capt C, Cuccarini V, Bruzzone MG, Di Meco F, Legnani FG, Ferroli P, Acerbi F, Pallini R, D'Alessandris QG, Olivi A, Gagliardi F, Snider S, Mortini P, Patane M, Fiocchi A, Berno V, Poliani PL, Finocchiaro G, Russo C, Ciceri F, Naldini L. Tumor-targeted interferon-alpha gene therapy for glioblastoma: a phase 1 trial. Nat Med. 2026 Jun;32(6):2216-2226. doi: 10.1038/s41591-026-04419-1. Epub 2026 Jun 1.

    PubMed 42225991

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Temferon in people with Glioblastoma Multiforme, run by Genenta Science at 3 sites in Italy.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 16 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 11 Jun 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 3 sites in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was stopped early (reason given: LVLP (pt GBM-01034) took place on 27may2026. The 2 remaining slots allocated by the protocol for the additional cohort to generate safety data prior to study Part B will not be filled. No safety concerns. Benefit-risk profile unchanged.). Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Tolerability and safety of Temferon over the first 90 days following administration as determined by the incidence of adverse events (time frame: 90 days). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03866109, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 Jun 2026.

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