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Multiple Myeloma

Neoplasms, Plasma Cell

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Interferons

Autologous CD34+-enriched hematopoietic progenitor cells exposed ex vivo to a specific lentiviral vector encoding for the human IFN-ɑ2 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 IFN-ɑ2 expression in HSPCs, thereby further increasing the specificity of the delivery strategy for their Tie2 expressing myeloid cell progeny.

Temferon

Fabio Ciceri, MD

This is a non-randomized, open label, phase I/II, 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-ɑ2 expression, which will be administered to up to 9 patients affected by multiple myeloma in early relapse after intensive front line treatment.

This is a non-randomized, open label, single center, phase I/II, therapeutic exploratory, dose-escalation, prospective study, involving a single intravenous infusion of Temferon, an investigational advanced therapy consisting of autologous CD34+-enriched hematopoietic stem and progenitor cells (HSPCs) exposed to transduction with a third-generation, vesicular stomatitis virus-G (VSV-G) pseudo-typed lentiviral vector driving myeloid-specific interferon-ɑ2 (IFN-ɑ2) expression, which will be administered to up to 9 patients affected by multiple myeloma in early relapse after intensive front line treatment. The study will recruit, treat and follow-up patients at a specialist hematology and bone marrow transplantation unit at Ospedale San Raffaele (OSR) in Milan, Italy.

The study will enrol multiple myeloma patients that have experienced an early relapse after intensive front line treatment, have been treated with an approved second line combination treatment regimen and obtained at least a very good partial remission (VGPR) according to International Myeloma Working Group (IMWG) criteria. Once the written informed consent is obtained, and screening procedures have been completed, harvesting of HSPCs will occur. Patients will be offered maintenance treatment during Temferon production and release. Upon Temferon release for clinical use, patients will be admitted to the transplantation unit for receipt of a reduced-intensity conditioning regimen consisting of melphalan. This will be followed by autologous stem cell transplant (ASCT) and administration of Temferon. In-patient monitoring will occur until hematological recovery occurs. Thereafter, regular follow-up of patients will occur up to 2 years (+730 days). At the +730 day visit, patients will be invited to participate in a long term follow-up study which will last for an additional 6 years.

3 cohorts of 3 patients will receive escalating doses of Temferon.

In the event that MM disease progression occurs, patients will be managed according to best clinical practice.

A Phase I/II Study Evaluating Temferon in Multiple Myeloma Patients With Early Relapse After Front Line Therapy (TEM-MM)

A Phase I/II Dose Escalation Study Evaluating Safety and Activity of Autologous CD34+-Enriched Hematopoietic Progenitor Cells Genetically Modified With a Lentiviral Vector Encoding for the Human Interferon-ɑ2 Gene in Multiple Myeloma Patients With Early Relapse After Intensive Front Line Therapy

0 participants analyzed. All the patients were withdrawn before treatment

IRCCS San Raffaele

Genenta Science

No treatment related adverse events were reported as Temferon was not adminsitered

3 patients recruited but did not receive Temferon

Untreated Patients

3 patients recruited into the study but no patients received Temferon. Study terminated due to inability to recruit additional patients in view of the ongoing COVID-19 pandemic

Patient Recruitment

Age, Categorical

Age, Continuous

Sex: Female, Male

Race (NIH/OMB)

Race/Ethnicity, Customized

Italy

Region of Enrollment

Although 3 patients were recruited, no patients received Temferon

Chief Medical Officer

3 Patients were recruited but did not receive Temferon

Tolerability and Safety of Temferon Over the First 90 Days Following Administration as Determined by the Incidence of CTCAEs

Long Term Tolerability and Safety of Temferon as Determined by the Incidence of CTCAEs

Proportion of Patients Achieving Hematologic 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) in the Absence of Transfusions

Determine the Maximum Tolerated Dose of Temferon

Identify Presence of Transduced Myeloid Cells in Bone Marrow as Determined by Vector Copy Number

Identify Presence of Transduced Myeloid Cells in Peripheral Blood as Determined by Vector Copy Number

Identify Persistence of Transduced Myeloid Cells in Bone Marrow and Peripheral Blood as Determined by Vector Copy Number

Determine Clinical Response in Patients as Determined by IMWG Response Criteria

Fraction of Patients Achieving Complete Response With Minimal Residual Disease (MRD) Negativity

Determine Progression Free Survival in Patients

Determine Overall Survival in Patients

Changes in Functional Status (Eastern Cooperative Oncology Group, ECOG)

Changes in Functional Status (Karnofsky)

Changes in Quality of Life: European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30

Changes in Quality of Life: European Organisation for Research and Treatment of Cancer (EORTC) QLQ-MY20

Autologous CD34+-enriched hematopoietic progenitor cells exposed ex vivo to a specific lentiviral vector encoding for the human IFN-ɑ2 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 IFN-ɑ2 expression in HSPCs, thereby further increasing the specificity of the delivery strategy for their Tie2 expressing myeloid cell progeny.

Temferon: Genetically modified autologous HSPCs

Overall Study

Glioblastoma

Astrocytoma

Glioma

Neoplasms, Neuroepithelial

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms, Glandular and Epithelial

Neoplasms, Nerve Tissue

Neuroepithelioma

Interferon-alpha

Interferon alpha-2

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.

Carlo Russo, MD

Stefania Mazzoleni, PhD

Marica Eoli, MD

Alessandro Olivi, MD

Gaetano Finocchiaro, MD

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.

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.

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;

A Study Evaluating Temferon in Patients With Glioblastoma & 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

Routine clinical and laboratory surveillance

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.

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

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

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

European Organisation for Research and Treatment of Cancer BN20 questionnaire

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
A Phase I/II Study Evaluating Temferon in Multiple Myeloma Patients With Early Relapse After Front Line Therapy (TEM-MM)	NCT03875495	Multiple Myelom...	Temferon	18 Years - 70 Years	Genenta Science
A Study Evaluating Temferon in Patients With Glioblastoma & Unmethylated MGMT	NCT03866109	Glioblastoma Mu...	Temferon	18 Years - 70 Years	Genenta Science
A Phase I/II Study Evaluating Temferon in Multiple Myeloma Patients With Early Relapse After Front Line Therapy (TEM-MM)	NCT03875495	Multiple Myelom...	Temferon	18 Years - 70 Years	Genenta Science

Spots Global Cancer Trial Database for temferon

Every month we try and update this database with for temferon cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Spots Global Cancer Trial Database for temferon

Every month we try and update this database with for temferon cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for temferon cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.