Chemotherapy-naive slowly progressive asymptomatic multiple myeloma with rising (at least 10%) M-protein concentration displayed on two occasions separated by an interval of at least 4 weeks within the last 18 months, or Stage II or III multiple myeloma who have experienced a treatment-free interval of at least 3 months with a stable response/plateau phase following anti-tumor therapy MedDRA version: 14.1 Level: PT Classification code 10028228 Term: Multiple myeloma System Organ Class: 10029
Conditions
Interventions
Product Name: L-BLP25 (Stimuvax®)
Product Code: EMD531444
Pharmaceutical Form: Powder and solvent for suspension for injection
Current Sponsor code: EMD531444
Other descriptive name: L-BLP25 reconstit
Sponsors
Merck KGaA
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Documented previously untreated, MUC1-expressing, slowly progressive asymptomatic multiple myeloma with an increasing M-protein concentration (at least 10%) displayed on two occasions separated by an interval of at least 4 weeks within the last 18 months or Documented MUC1-expressing stage II or III multiple myeloma with a treatment-free interval of at least 3 months following prior anti-tumor therapy, and fulfilling criteria for having a stable response/plateau phase. Signed written informed consent MUC1-expressing myeloma cells in the bone marrow =18 years of age Life expectancy of at least 6 months ECOG performance status of =1 at study entry Effective contraception for both male and female subjects, if the possibility of conception exists A platelet count =100 x 109/L, WBC =2.5 x 109/L, and hemoglobin =90 g/L Total bilirubin =1.5 x upper reference range AST 2.5 = x upper reference range Serum creatinine =2 x upper reference Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: Pre-Therapies: Previous exposure to MUC1 targeting therapy Radiotherapy or any investigational drug in the 30 days before the start of treatment in this study Receipt of immunotherapy (e.g. interferons, tumor necrosis factor [TNF], interleukins, or biological response modifiers [granulocyte macrophage colony stimulating factor {GMCSF}, granulocyte colony stimulating factor {G-CSF}, macrophage-colony stimulating factor {M-CSF}], monoclonal antibodies) within 4 weeks (28 days) prior to randomization. Any preexisting medical condition requiring chronic oral or intravenous steroid or immunosuppressive therapy except for maintenance doses of prednisone of = 10 mg/day. Medical Conditions: Autoimmune disease that in the opinion of the investigator could compromise the safety of the subject in this study Hereditary or congenital immunodeficiencies Known hypersensitivity reaction to any of the components of study treatments Clinically significant cardiac disease, e.g., New York Heart Association (NYHA) classes III-IV; unstable angina, uncontrolled arrhythmia or uncontrolled hypertension, myocardial infarction in the previous 6 months Other previous malignancies within 5 years, with exception of a history of a previous basal cell carcinoma of the skin, carcinoma in situ of uterine cervix, gastrointestinal intramucosal carcinoma. Known Hepatitis B and/or C. Splenectomy Standard Safety: ? Known alcohol or drug abuse ? Medical or psychological conditions that would not permit the subject to complete the study or sign informed consent ? Significant disease which, in the investigator’s opinion, would exclude the subject from the study ? Pregnant or breast-feeding women, women of childbearing potential, unless using effective contraception as determined by the investigator. Subjects whom the investigator considers may be at risk of pregnancy will have a pregnancy test performed per institutional standard ? Participation in another clinical study within the past 30 days ? Legal incapacity or limited legal capacity ? Concurrent treatment with a non-permitted drug ? Any other reason that, in the opinion of the investigator, precludes the subject from participating in the study
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Primary objective: To ascertain whether vaccination with L-BLP25 induces a MUC1-specific T-cell response in subjects with either: Chemotherapy-naïve, slowly progressive, asymptomatic MM with rising (at least 10%) M-protein concentrations displayed on 2 occasions separated by an interval of at least 4 weeks, within the last 18 months, or Stage II or III MM who have experienced a treatment-free interval of at least 3 months with a stable response/plateau phase following anti-tumor therapy.;Secondary Objective: Secondary objectives of this trial are: To characterize the safety and tolerability of vaccination with L-BLP25 in the 2 treatment groups, with pre-treatment with cyclophosphamide (300 mg/ m² i.v.), either as a single dose up front or as a dose up front with additional doses prior to week 5 and prior to each maintenance vaccination. Treatment with cyclophosphamide in arm B was stopped with amendment 3 of the protocol. To characterize the nature of the immune reaction. To collect information on a linkage of the immunological response with HLA restriction To determine the objective clinical response (as defined by Blade Criteria, see Appendix C) in MM subjects receiving L-BLP25 vaccination. To determine the time to progression. To determine the time to anti-tumor therapy.;Primary end point(s): Anti-MUC1 T-cell response | — |
Countries
Sweden
Outcome results
None listed