Resumen

Elegibilidad

Detalles del diseño

Brazos e Intervenciones

Medidas de resultado

Sitios del ensayo

Fuente: NCT03866109

Activo, sin reclutamiento

TEM-GBM: A Study Evaluating Temferon in Patients with Glioblastoma & Unmethylated MGMT

Intervencionista

Fase 1/2

IRCCS Ospedale San Raffaele

Patrocinador: Genenta Science

Última actualización: 6 de enero de 2025
Aviso: La información proviene de registros públicos y puede no reflejar cambios en tiempo real en el centro local.

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.

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Categoría de tratamiento

Otros medicamentos

Erforderliche Mutationen

Ninguna

Ensayo iniciado

5 de marzo de 2019

Última actualización por el patrocinador

6 de enero de 2025

Finalización estimada

9 de diciembre de 2025

Contacto del estudio

Nombre:Carlo Russo, MD

Correo electrónico:info-trial@genenta.com

Teléfono:+39 02 2643 3982

Nombre:Stefania Mazzoleni, PhD

Correo electrónico:info-trial@genenta.com

Teléfono:+39 02 2643 3982

Elegibilidad

Criterios de inclusión

* 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.

Criterios de exclusión

* 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.

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Detalles del diseño

AsignaciónN/A

Modelo de intervenciónSequential Assignment

EnmascaramientoNone (Open Label)

Número a inscribir27

Brazos e Intervenciones

Brazos

Intervenciones

Tipo: Experimental

Descripción: 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.

Intervenciones:

Temferon

Medidas de resultado

Medidas de resultado primarias

Tolerability and safety of Temferon over the first 90 days following administration as determined by the incidence of adverse events90 days

Routine clinical and laboratory surveillance

Medidas de resultado secundarias

Long term tolerability and safety of Temferon as determined by the incidence of adverse events2 years

Routine clinical and laboratory surveillance

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

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.

Determine the maximum tolerated dose of Temferon30 days

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

Identify presence of transduced myeloid cells in bone marrow as determined by vector copy numberOver 2 years

VCN

Incidence of adverse events attributed to the conditioning regimenDay +30

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

Identify presence of transduced myeloid cells in peripheral blood as determined by vector copy numberOver 2 years

VCN

Determine clinical response in patients as determined by iRANO criteriaOver 2 years

iRANO criteria

Determine progression free survival in patientsOver 2 years

MRI

Determine overall survival in patients2 years

Survival data

Changes in functional status (Karnofsky)2 years

Karnofsky assessment

Changes in Quality of Life (European Organisation for Research and Treatment of Cancer EORTC C30)2 years

EORTC C30 questionnaire

Changes in Quality of Life (BN20)2 years

European Organisation for Research and Treatment of Cancer BN20 questionnaire

Changes in functional status (Eastern Cooperative Oncology Group)2 years

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

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Sitios del ensayo

Este estudio tiene 2 sitios de ensayo

IRCCS Ospedale San Raffaele

Milano, Milano, IT

Reclutando

Milan, 20133 IT

Fondazione IRCCS Istituto Neurologico "Carlo Besta"

Aún no recluta

Rome, IT

Policlinico Universitario Fondazione Agostino Gemelli

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