A Phase I/II Study Evaluating Temferon in Multiple Myeloma Patients With Early Relapse After Front Line Therapy (TEM-MM)
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|ClinicalTrials.gov Identifier: NCT03875495|
Recruitment Status : Recruiting
First Posted : March 14, 2019
Last Update Posted : March 14, 2019
|Condition or disease||Intervention/treatment||Phase|
|Multiple Myeloma||Drug: Temferon||Phase 1 Phase 2|
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.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||9 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||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|
|Actual Study Start Date :||March 6, 2019|
|Estimated Primary Completion Date :||March 2023|
|Estimated Study Completion Date :||March 2023|
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.
Genetically modified autologous 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 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 [ 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: Up to 2 years ]
- Identify presence of transduced myeloid cells in peripheral blood as determined by vector copy number [ Time Frame: Up to 2 years ]
- Identify persistence of transduced myeloid cells in bone marrow and peripheral blood as determined by vector copy number [ Time Frame: At least 12 weeks ]
- Determine clinical response in patients as determined by IMWG response criteria [ Time Frame: Up to 2 years ]
- Fraction of patients achieving complete response with Minimal Residual Disease (MRD) negativity [ Time Frame: Up to 2 years ]
- Determine progression free survival in patients [ Time Frame: Up to 2 years ]
- Determine overall survival in patients [ Time Frame: 2 years ]
- Changes in functional status (Eastern Cooperative Oncology Group, ECOG) [ Time Frame: 2 years ]
- Changes in functional status (Karnofsky) [ Time Frame: 2 years ]
- Changes in Quality of Life: European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30 [ Time Frame: 2 years ]
- Changes in Quality of Life: European Organisation for Research and Treatment of Cancer (EORTC) QLQ-MY20 [ 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): NCT03875495
|Contact: Carlo Russo, MD||+39 02 2643 firstname.lastname@example.org|
|Contact: Andrew Zambanini, MD||+39 02 2643 email@example.com|
|Ospedale San Raffaele||Recruiting|
|Milan, Italy, 20132|
|Contact: Fabio Ciceri, MD|
|Principal Investigator:||Fabio Ciceri, MD||Ospedale San Raffaele, Milan, Italy|