Clinical trial NCT01094548: Study of Tecemotide (L-BLP25) in Subjects With Slowly Progressive Multiple Myeloma With no Symptoms and Who Have Had no Chemotherapy
Official title: A Randomized, Open-label, Phase II Study With Stimuvax® (L-BLP25 or BLP25 Liposome Vaccine) in Subjects With Either Chemotherapy-naïve, Slowly Progressive, Asymptomatic Multiple Myeloma or With Stage II/III Multiple Myeloma in Stable Response/Plateau Phase Following Anti-tumor Therapy
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Multiple Myeloma
Keywords: L-BLP25 liposome
Multiple myeloma
Lead sponsor: Merck KGaA, Darmstadt, Germany
Sponsor class: INDUSTRY
First posted: 2010-03-29
Enrollment: 34
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Tecemotide (L-BLP25) is believed to induce a Mucinous glycoprotein 1 (MUC1)-specific T-cell response after vaccination. The primary purpose of this study is to ascertain whether vaccination with tecemotide (L-BLP25) induces a MUC1-specific T-cell response in slowly progressive or chemotherapy naive multiple myeloma subjects.


Eligibility criteria: Inclusion Criteria:

* Documented previously untreated, Mucinous glycoprotein 1 (MUC1)-expressing, slowly progressive asymptomatic multiple myeloma with an increasing M-protein concentration 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
* Greater than or equal to (\>=) 18 years of age
* Life expectancy of at least 6 months
* Eastern Cooperative Oncology Group (ECOG) performance status of less than or equal to (\<=) 1 at study entry
* Effective contraception for both male and female subjects, if the possibility of conception exists
* A platelet count \>=100 x 10\^9/Liter, white blood cells \>=2.5 x 10\^9/Liter, and hemoglobin \>=90 gram per liter (g/L)
* Total bilirubin \<= 1.5 x upper reference range
* Aspartate aminotransferase (AST) \<= 2.5 x upper reference range
* Serum creatinine \<= 2 x upper reference

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 (Example: interferons, tumor necrosis factor \[TNF\], interleukins, or biological response modifiers \[granulocyte macrophage colony stimulating factor {GM-CSF}, granulocyte colony stimulating factor {G-CSF}, macrophage-colony stimulating factor {M-CSF}\], 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 milligram per day (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, Example: 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

Primary outcomes:
measure: Number of Participants With Overall Induced Mucinous Glycoprotein-1 (MUC-1)-Specific Immune Response
timeFrame: From the date of randomization up to Week 104
Secondary outcomes:
measure: Number of Participants With Baseline Immune Response and Initial Increase of MUC1 Specific Immune Response
timeFrame: Baseline and Week 9
measure: Number of Participants With Overall Induced Immune Response by Human Leukocyte-associated Antigen (HLA) Type
timeFrame: From the date of randomization up to Week 104
measure: Percentage of Participants With Objective Clinical Response (Complete Response [CR], or Partial Response [PR], or Minimal Response [MR]
timeFrame: From the date of randomization up to Month 48
measure: Time to Progression (TTP)
timeFrame: From the date of randomization up to Month 48
measure: Time to Anti-tumor Therapy
timeFrame: From the date of randomization up to Month 48
measure: Number of Participants With Treatment Emergent Adverse Events (TEAEs),Serious TEAEs, TEAEs of Grade 3 or 4 According to NCI-CTCAE v3.0, TEAEs Leading to Discontinuation and Injection Site Reactions (ISRs)
timeFrame: From the first dose of study drug administration up to 42 days after the last dose of study drug administration or clinical data cut-off date (07 March 2012)
Other outcomes:
Locations:
city: Darmstadt
country: Germany
facility: Please Contact the Merck KGaA Communication Center
Study officials:
affiliation: Merck KGaA, Darmstadt, Germany
name: Medical Responsible
role: STUDY_DIRECTOR
References:
citation: Rossmann E, Österborg A, Löfvenberg E, et al. Randomized Phase II Study of BLP25 Liposome Vaccine (L-BLP25) in Patients with Multiple Myeloma. Am Soc Hematol. 53rd Annual Meeting, Dec 2011, Poster 2927.
citation: Rossmann E, Osterborg A, Lofvenberg E, Choudhury A, Forssmann U, von Heydebreck A, Schroder A, Mellstedt H. Mucin 1-specific active cancer immunotherapy with tecemotide (L-BLP25) in patients with multiple myeloma: an exploratory study. Hum Vaccin Immunother. 2014;10(11):3394-408. doi: 10.4161/hv.29918.