A Phase I/IIa Study Evaluating Temferon in Patients With Glioblastoma & Unmethylated MGMT (TEM-GBM)
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|ClinicalTrials.gov Identifier: NCT03866109|
Recruitment Status : Recruiting
First Posted : March 7, 2019
Last Update Posted : March 14, 2019
|Condition or disease||Intervention/treatment||Phase|
|Glioblastoma Multiforme||Drug: Temferon||Phase 1 Phase 2|
This is a non-randomized, open label, two center, 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 21 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 unit (Istituto Neurologico Carlo Besta, INCB) in Milan, Italy. Administration of Temferon and hematological follow up will take place at a specialist hematology and bone marrow transplantation unit at Ospedale San Raffaele (OSR) in Milan, Italy.
Potentially eligible patients will be identified at INCB 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 at OSR. A standard of care regimen lasting approximately 6 weeks, will then take place at INCB. During this time, Temferon manufacturing will occur. Following completion of radiotherapy, patients will be admitted to OSR for receipt of a conditioning regimen consisting of BCNU and thiotepa. This will be followed by administration of Temferon. In-patient monitoring at OSR 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 performed at INCB and some assessments/procedures at OSR. 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, 3 cohorts of 3 patients will receive escalating doses of Temferon. On completion of Part A, a single dose of Temferon will be selected to be studied in up to a further 12 patients in Part B. Criteria for study eligibility are the same for both Part A and Part B.
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.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||21 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|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|
|Actual Study Start Date :||March 5, 2019|
|Estimated Primary Completion Date :||December 2022|
|Estimated Study Completion Date :||December 2022|
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.
Genetically modified HSPCs
- Tolerability and safety of Temferon over the first 90 days following administration as determined by the incidence of CTCAEs [ Time Frame: 90 days ]
- Long term tolerability and safety of Temferon as determined by the incidence of CTCAEs [ Time Frame: 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) [ Time Frame: 30 days ]
- Determine the maximum tolerated dose of Temferon [ Time Frame: 30 days ]
- Identify presence of transduced myeloid cells in bone marrow as determined by vector copy number [ Time Frame: Over 2 years ]
- Identify presence of transduced myeloid cells in peripheral blood as determined by vector copy number [ Time Frame: Over 2 years ]
- Identify persistence of transduced myeloid cells in peripheral blood as determined by vector copy number [ Time Frame: At least 12 weeks ]
- Determine clinical response in patients as determined by iRANO criteria [ Time Frame: Over 2 years ]
- Determine progression free survival in patients [ Time Frame: Over 2 years ]
- Determine overall survival in patients [ Time Frame: 2 years ]
- Changes in functional status (ECOG) [ Time Frame: 2 years ]
- Changes in functional status (Karnofsky) [ Time Frame: 2 years ]
- Changes in Quality of Life (EORTC C30) [ Time Frame: 2 years ]
- Changes in Quality of Life (BN20) [ Time Frame: 2 years ]
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03866109
|Contact: Carlo Russo, MD||+39 02 2643 firstname.lastname@example.org|
|Contact: Andrew Zambanini, MD||+39 02 2643 email@example.com|
|Ospedale San Raffaele||Enrolling by invitation|
|Milan, Italy, 20132|
|Fondazione IRCCS Istituto Neurologico "Carlo Besta"||Recruiting|
|Milan, Italy, 20133|
|Contact: Gaetano Finocchiaro, MD|
|Principal Investigator:||Gaetano Finocchiaro, MD||Fondazione IRCCS Istituto Neurologico "Carlo Besta"|