A Phase II study with Stimuvax® (L-BLP25 liposome vaccine) in subjects with either chemotherapy-naive, slowly progressive asymptomatic multiple myeloma or with stage II/ III multiple myeloma following chemotherapy

• Register: EUCTR
• Last refreshed on: 26 June 2012
• Main ID: EUCTR2006-001810-33-SE
• Date of registration: 07/08/2007
• Primary sponsor: Merck KGaA
• Public title: A Phase II study with Stimuvax® (L-BLP25 liposome vaccine) in subjects with either chemotherapy-naive, slowly progressive asymptomatic multiple myeloma or with stage II/ III multiple myeloma following chemotherapy
• Scientific title: A Phase II study with Stimuvax® (L-BLP25 liposome vaccine) in subjects with either chemotherapy-naive, slowly progressive asymptomatic multiple myeloma or with stage II/ III multiple myeloma following chemotherapy
• Date of first enrolment: 27/09/2007
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2006-001810-33
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes; Randomised: yes; Open: yes; Single blind: no; Double blind: no; Parallel group: yes; Cross over: no; Other: no; If controlled, specify comparator, Other Medicinial Product: no; Placebo: no; Other: yes

Countries of recruitment

Sweden

Key inclusion & exclusion 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:
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


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

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: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Intervention(s)

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 reconstituted
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 23.395-

Trade Name: Sendoxan 1000 mg(1g)
Pharmaceutical Form: Powder for solution for injection
INN or Proposed INN: Cyclophosphamide
CAS Number: 50-18-0
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 1000-

Primary Outcome(s)

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.

Primary end point(s): Anti-MUC1 T-cell response

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.

Secondary ID(s)

EMR63325-008