An Open-label, Randomized Study of Subcutaneous and Intravenous VELCADE® in Subjects With Previously Treated Multiple Myeloma

• Register: EUCTR
• Last refreshed on: 19 March 2012
• Main ID: EUCTR2008-000952-28-GB
• Date of registration: 27/11/2008
• Prospective Registration: Yes
• Primary sponsor: Janssen-Cilag International NV (JCI)
• Public title: An Open-label, Randomized Study of Subcutaneous and Intravenous VELCADE® in Subjects With Previously Treated Multiple Myeloma
• Scientific title: An Open-label, Randomized Study of Subcutaneous and Intravenous VELCADE® in Subjects With Previously Treated Multiple Myeloma
• Date of first enrolment: 15/01/2009
• Target sample size: 216
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2008-000952-28
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: yes Single blind: Double blind: Parallel group: yes Cross over: Other: If controlled, specify comparator, Other Medicinial Product: Placebo: Other: yes Other specify the comparator: IV Arm

Countries of recruitment

Belgium, France, Germany, United Kingdom

Key inclusion & exclusion criteria

Inclusion criteria:
Potential subjects must satisfy the following criteria to be enrolled in the study:
1. Male or female subjects 18 years or older
2. Diagnosis of multiple myeloma based on the standard criteria described in Attachment 1.
3. Measurable, secretory multiple myeloma defined as serum monoclonal IgG of =10 g/L, serum monoclonal IgA or IgE =5 g/L, or serum monoclonal IgD =0.5g/L; or urine M protein of =200 mg/24 hr
4. Relapse or progression of myeloma following prior systemic antineoplastic therapy. Relapse or progression is defined by any of the following:
· Reappearance of measurable disease (as defined above) following CR
· =25% increase in serum or urine M-protein
· Development of new or worsening lytic bone disease
· New plasmacytomas or =50% increase in the longest dimension of an existing plasmacytoma
· Worsening hypercalcemia (corrected serum Ca >11.5 mg/dL [2.8 mmol/L]) due to multiple myeloma
5. Karnofsky performance status =70% (Attachment 2)
6. Platelet count =50 x 10^9/L without transfusion support within 7 days before the laboratory test
7. Hemoglobin =8 g/dL (=4.96 mmol/L) without transfusion support within 7 days before the laboratory test.
8. Absolute neutrophil count (ANC) =0.75 x 10^9/L.
9. Corrected serum Ca <14 mg/dL (<3.5 mmol/L)
10. Aspartate aminotransferase (AST) =2.5X upper limit of normal (ULN)
11. Alanine aminotransferase (ALT) =2.5X ULN
12. Total bilirubin =1.5X ULN (except in subjects with congenital bilirubinemia, such as Gilbert syndrome)
13. Creatinine clearance =20 mL/min, calculated using the formula in Attachment 3.
14. Toxic effects of previous therapy or surgery have resolved to CTCAE Grade 1 or better
15. Women who are not post-menopausal or surgically sterile must have a negative pregnancy test and agree to use an acceptable method of birth control during the study until 30 days after the last dose of study drug.
16. Men must agree to not father a child and agree to use a latex condom during treatment and for 30 days after the last dose of study drug, even if they have had a successful vasectomy, if their partners are of childbearing potential.
17. Voluntary written informed consent must be given before performance of any study related procedure not part of normal medical care, with the understanding that consent may be withdrawn by the subject at any time without prejudice to future medical care.

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:
Potential subjects who meet any of the following criteria will be excluded from participating in the study:
1. Previous treatment with VELCADE®
2. More than 3 previous lines of therapy (separate lines of therapy are defined as single or combination therapies that are either separated by disease progression or by a >6 month treatment-free interval)
3. Peripheral neuropathy or neuropathic pain of NCI CTCAE Grade=2
4. Any of the following within 3 weeks prior to randomization: antineoplastic or experimental therapy, corticosteroid use above10 mg/day (prednisone or equivalent), or plasmapheresis
5. Any of the following within 2 weeks prior to randomization: radiation therapy, major surgery (kyphoplasty is not considered major surgery)
6. Prior malignancy other than multiple myeloma diagnosed or treated within the last 2 years, with the exception of completely resected carcinoma in situ or basal/squamous carcinoma of the skin
7. Myocardial infarction within 6 months prior to enrollment or New York Heart Association (NYHA) Class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or clinically significant conduction system abnormalities
8. Concurrent medical condition or disease (e.g., active systemic infection, uncontrolled diabetes, pericardial disease, acute diffuse infiltrative pulmonary disease, therapeutic use of anticoagulants) that is likely to interfere with study procedures or results (including local injection tolerability), that in the opinion of the investigator would constitute a hazard for participating in this study
9. History of allergic reaction attributable to dexamethasone or its constituents, or compounds containing boron or mannitol



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

Health Condition(s) or Problem(s) studied

The subject population comprises adult male and female subjects with multiple myeloma that has relapsed or progressed after prior systemic antineoplastic therapy, presence of measurable secretory disease, Karnofsky performance status score greater than or equal to 70%, and clinical hematology and chemistry laboratory values that meet predefined criteria
MedDRA version: 9.1 Level: LLT Classification code 10028228 Term: Multiple myeloma

Intervention(s)

Trade Name: VELCADE
Product Name: VELCADE
Product Code: JNJ-26866138
Pharmaceutical Form: Powder for solution for injection
INN or Proposed INN: VELCADE (bortezomib)
CAS Number: 179324-69-7
Current Sponsor code: JNJ-26866138
Other descriptive name: bortezomib
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 3.5-

Trade Name: Fortecortin
Product Name: Fortecortin (dexamethasone)
Pharmaceutical Form: Tablet
INN or Proposed INN: Dexamethasone
CAS Number: 50-02-2
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 4-

Trade Name: Fortecortin (dexamethasone)
Product Name: Fortecortin (dexamethasone)
Pharmaceutical Form: Tablet
INN or Proposed INN: Dexamethasone
CAS Number: 50-02-2
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 8-

Primary Outcome(s)

Secondary Objective: The secondary objectives are:
- to determine the CR, nCR and VGPR rates after 4 cycles of single-agent VELCADE®, the ORR after 8 cycles including the effect of adding dexamethasone, the duration of response (DOR), time to disease progression (TTP), progression-free survival (PFS), 1-year survival, and time to response following VELCADE® treatment, administered either SC or IV,
- to evaluate the safety and tolerability of the 2 routes of administration, including the local tolerability of SC administration
- to describe the plasma pharmacokinetics and pharmacodynamics (via 20S proteasome inhibition assay in whole blood) of SC administered VELCADE® as compared to IV administered VELCADE®

Main Objective: The primary objective is to compare the overall response rate ORR (CR+PR), after 4 cycles, of subcutaneously (SC) administered VELCADE® and intravenously (IV) administered VELCADE® in patients with previously treated multiple myeloma.

Primary end point(s): The primary endpoint of the study is the overall response rate ORR (CR+PR) after 4 cycles (prior to the addition of dexamethasone) for the SC group and the IV group.

Secondary ID(s)

26866138-MMY-3021

2008-000952-28-DE