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.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
9
Genetically modified autologous HSPCs
Ospedale San Raffaele
Milan, Italy
Tolerability and Safety of Temferon Over the First 90 Days Following Administration as Determined by the Incidence of CTCAEs
0 participants analyzed. All the patients were withdrawn before treatment
Time frame: 90 days
Long Term Tolerability and Safety of Temferon as Determined by the Incidence of CTCAEs
0 participants analyzed. All the patients were withdrawn before treatment
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
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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