Multiple myeloma in early relapse after intensive front line therapy MedDRA version: 20.0 Level: LLT Classification code 10028228 Term: Multiple myeloma System Organ Class: 100000004864
Conditions
Interventions
Product Name: Temferon
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: Temferon
Current Sponsor code: Temferon
Other descriptive name: HSPC autologhe geneticamente modi
Sponsors
OSPEDALE SAN RAFFAELE
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Multiple myeloma patients with early relapse after intensive front-line treatment and disease measurable by serum biomarkers that have obtained at least a VGPR after second-line salvage treatment; 2. Able and willing to provide written informed consent; 3. Able to comply with study protocol and procedures; 4. Male or Female; 5. Age 18-70 years; 6. Fit patients: Performance status scores: ECOG 70%; Life expectancy of = 6 months; 7. Adequate cardiac, renal, hepatic and pulmonary functions; 8. 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; 9. 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. Are the trial subjects under 18? no Number of subjects for this age range: 1 F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 8 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 1
Exclusion criteria
Exclusion criteria: 1. Use of other investigational agents within 4 weeks prior to experimental treatment (within 6 weeks if use of long-acting agents); 2. Severe active viral, bacterial, or fungal infection at eligibility evaluation; 3. Active autoimmune disease or a history of clinically relevant autoimmune manifestations requiring immunosuppressive treatment, i.e. psoriasis, systemic lupus erythematosus, rheumatoid arthritis, vasculitis, immune-mediated peripheral neuropathies; 4. Sarcoidosis requiring active steroid or immunosuppressive treatment; 5. Primary amyloidosis; 6. History of neuropsychiatric illness including severe depression, schizophrenia, bipolar disorders, impaired cognitive function, dementia or suicidal tendency; 7. Neuropathy > grade 2; 8. History of severe cardiovascular disease such as prior stroke, coronary artery disease requiring intervention, unresolved arrhythmias; 9. Malignant neoplasia (except local skin cancer or cervical intraepithelial neoplasia) or family history of familial cancer syndromes; 10. Myelodysplasia, cytogenetic or molecular alterations specifically associated with clonal hematopoiesis of the myeloid lineage, or other serious hematological disorder other than the plasma cell dyscrasia; 11.Other clinical conditions judged by the Investigator non-compatible with the study procedures; 12. Positivity for HIV-1, HIV-2 (serology or RNA), and/or HbsAg and/or HBV DNA and/or HCV RNA (or negative HCV RNA but on antiviral treatment) and/or Treponema Pallidum or Mycoplasma active infection; 13. Active alcohol or substance abuse within 6 months of the study; 14. Pregnancy or lactation; 15. Previous allogeneic bone marrow transplantation, kidney or liver transplant, or gene therapy; 16. Prior to conditioning: inability to meet the target mobilization cell number after at least 2 attempts of HSPC collection.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate safety and tolerability of escalating doses of Temferon in multiple myeloma patients with early relapse after intensive front line therapy.;Secondary Objective: To evaluate biological activity and efficacy of escalating doses of Temferon as maintenance/consolidation treatment in multiple myeloma patients with early relapse after intensive front line therapy.;Primary end point(s): - Engraftment of Temferon after reduced intensity conditioning (vector copy number [VCN] > 0.07 in myeloid cells between Day +30 and Day +100 in at least 2 patients); - The proportion of patients achieving hematologic recovery by Day +30 from ASCT with non-manipulated autologous HSPC and infusion of Temferon; - Safety of Temferon measured through the 24 months post Temferon infusion.;Timepoint(s) of evaluation of this end point: Multiple timepoints up to 2 years | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): - Presence of an IFN-alfa gene signature in the bone marrow (BM) of Temferon-treated patients. - Presence of transduced myeloid cells in BM aspirate and peripheral blood (PB) at Day +30 and Day +100 post Temferon infusion as determined by VCN. - Persistence of transduced myeloid cells in PB and BM as assessed by VCN for at least 12 weeks - Overall response rate (ORR) - Fraction of patients achieving complete response (CR) with minimal residual disease (MRD) levels = 10-5 and 10-6 on BM aspirate - Duration of maintenance of response during the 24 months post Temferon infusion - Progression-free survival (PFS) and overall survival (OS) at 24 months post Temferon infusion. - Change in health-related quality of life (HRQOL) at 6, 12 and 24 months post Temferon infusion compared to screening. - Change over time in performance status scores (ECOG and Karnofsky) through 24 months post Temferon infusion.;Timepoint(s) of evaluation of this end point: Multiple timepoints up to 2 years | — |
Countries
Italy
Contacts
Public ContactUfficio Ricerche Cliniche – Stem Ce
OSPEDALE SAN RAFFAELE
Outcome results
None listed