E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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 Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10028228 |
E.1.2 | Term | Multiple myeloma |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
|
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
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. |
|
E.2.2 | Secondary objectives of the trial |
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. |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal 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 |
|
E.4 | Principal 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 |
|
E.5 End points |
E.5.1 | Primary end point(s) |
Anti-MUC1 T-cell response |
|
E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
|
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | Yes |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.4.1 | Number of sites anticipated in Member State concerned | 1 |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
Study will be finished when both of the following conditions are met:
6 weeks after the last remaining subject received the last vaccination within this study, and when the primary study objective can be answered. |
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 3 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 0 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |