Study of Tecemotide (L-BLP25) in Subjects With Slowly Progressive Multiple Myeloma With no Symptoms and Who Have Had no Chemotherapy

NCT01094548 | Completed Phase 2 Results

• 1 other identifier: EMR63325-008
• Study Type: interventional
• Target: 34
• Locations: 1 country
• Sites: 1

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.

Conditions

Multiple Myeloma

Keywords

L-BLP25 liposome; Multiple myeloma

Outcome Measures

Primary Outcomes (1)

• Number of Participants With Overall Induced Mucinous Glycoprotein-1 (MUC-1)-Specific Immune Response

  The overall immune response was achieved at least for 2 timepoints; that is at least 1 parameter in at least 1 assay (Lymphoproliferation assay, enzyme-linked immunospot (ELISPOT) for interferon \[IFN\] gamma, and intracellular IFN gamma cytokine assay in peripheral blood mononuclear cell \[PBMC\]) with ratio to background \>=2, and ratio of background-corrected value to baseline \>=2;Specific immune response at a given timepoint 't' was considered as differences of log-scale values under stimulation (X vax,t ) to those of the respective unstimulated controls (Xneg,t, background values)were computed after certain assay-specific pre-processing steps: Yt = Xvax,t - Xneg,t; A participant was considered to show positive stimulation-induced immune response at timepoint 't' (POS\[t\]=1), upon fulfilling the following criteria: Yt =\>1 (That is at least a 2-fold higher value under stimulation than without stimulation). AVvax,t-1SEM vax,t \> AVneg,t+1SEMneg,t (ELISPOT and proliferation assay only).

  From the date of randomization up to Week 104

Secondary Outcomes (6)

• Number of Participants With Baseline Immune Response and Initial Increase of MUC1 Specific Immune Response

  Baseline and Week 9

• Number of Participants With Overall Induced Immune Response by Human Leukocyte-associated Antigen (HLA) Type

  From the date of randomization up to Week 104

• Percentage of Participants With Objective Clinical Response (Complete Response [CR], or Partial Response [PR], or Minimal Response [MR]

  From the date of randomization up to Month 48

• Time to Progression (TTP)

  From the date of randomization up to Month 48

• Time to Anti-tumor Therapy

  From the date of randomization up to Month 48

Study Arms (2)

Tecemotide (L-BLP25) plus single low dose cyclophosphamide

EXPERIMENTAL

Biological: Tecemotide (L-BLP25); Drug: Single low dose cyclophosphamide

Tecemotide (L-BLP25) plus multiple low dose cyclophosphamide

EXPERIMENTAL

Biological: Tecemotide (L-BLP25); Drug: Multiple low dose cyclophosphamide

Interventions

Tecemotide (L-BLP25) BIOLOGICAL

After receiving single low dose of cyclophosphamide, subjects will receive 8 consecutive weekly subcutaneous vaccinations with 806 microgram (mcg) of tecemotide (L-BLP25) at Weeks 1, 2, 3, 4, 5, 6, 7 and 8 followed by maintenance vaccinations (806 mcg of tecemotide (L-BLP25) at 6-Week intervals, commencing at Week 14, until disease progression requiring anti-tumor therapy is documented.

Also known as: Stimuvax

Tecemotide (L-BLP25) plus single low dose cyclophosphamide

Single low dose cyclophosphamide DRUG

An intravenous (IV) infusion of 300 milligram per square meter (mg/m\^2) (to a maximum 600 mg) of cyclophosphamide will be given 3 days before the first vaccine treatment.

Tecemotide (L-BLP25) plus single low dose cyclophosphamide

Multiple low dose cyclophosphamide DRUG

An IV infusion of 300 mg/m\^2 (to a maximum 600 mg) of cyclophosphamide will be given 3 days before the first vaccine treatment plus an intravenous dose of cyclophosphamide (300 mg/m\^2, to a maximum of 600 mg) 3 days prior to the tecemotide (LBLP25) administration at week 5 of the weekly treatment phase and 3 days prior to every tecemotide (L-BLP25) administration during the treatment phase with 6-Weekly administration of tecemotide (L-BLP25), commencing at Week 14 up to a maximum treatment period of 2 years.

Tecemotide (L-BLP25) plus multiple low dose cyclophosphamide

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Merck KGaA, Darmstadt, Germany: lead

Study Sites (1)

Please Contact the Merck KGaA Communication Center

Darmstadt, Germany

Location

Related Publications (2)

• 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.

  BACKGROUND

• 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.

  PMID: 25483677 DERIVED

MeSH Terms

Conditions

Multiple Myeloma

Interventions

L-BLP25; Single Person; Cyclophosphamide

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Marital Status; Family Characteristics; Demography; Population Characteristics; Socioeconomic Factors; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds

Results Point of Contact

• Title: Merck KGaA Communication Center
• Organization: Merck Healthcare, a business of Merck KGaA, Darmstadt, Germany

service@merckgroup.com

+49-6151-72-5200

Study Officials

• Medical Responsible

  Merck KGaA, Darmstadt, Germany

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 24, 2010
• First Posted: March 29, 2010
• Study Start: January 1, 2008
• Primary Completion: February 1, 2011
• Study Completion: March 1, 2012
• Last Updated: February 22, 2016
• Results First Posted: February 22, 2016

Record last verified: 2016-01

Locations

DE (1)