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A Study of Subcutaneous and Intravenous VELCADE in Patients With Previously Treated Multiple Myeloma

This study has been completed.
Sponsor:
Collaborator:
Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
Information provided by (Responsible Party):
Millennium Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier:
NCT00722566
First received: July 23, 2008
Last updated: October 6, 2011
Last verified: October 2011
Results First Received: August 30, 2011  
Study Type: Interventional
Study Design: Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Open Label;   Primary Purpose: Treatment
Condition: Multiple Myeloma
Interventions: Drug: VELCADE Administered by subcutaneous injection
Drug: VELCADE Administered by intravenous infusion

  Participant Flow
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Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
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Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
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Reporting Groups
  Description
VELCADE Subcutaneous VELCADE 1.3 mg/m^2 administered by subcutaneous injection on Days 1, 4, 8, and 11 of a 3-week cycle for 8 cycles.
VELCADE Intravenous VELCADE 1.3 mg/m^2 administered by intravenous infusion on Days 1, 4, 8, and 11 of a 3-week cycle for 8 cycles.

Participant Flow:   Overall Study
    VELCADE Subcutaneous     VELCADE Intravenous  
STARTED     148 [1]   74  
COMPLETED     81 [2]   39 [2]
NOT COMPLETED     67     35  
[1] One patient randomized and not dosed
[2] Completed 8 cycles



  Baseline Characteristics
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Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
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Reporting Groups
  Description
VELCADE Subcutaneous VELCADE 1.3 mg/m^2 administered by subcutaneous injection on Days 1, 4, 8, and 11 of a 3-week cycle for 8 cycles.
VELCADE Intravenous VELCADE 1.3 mg/m^2 administered by intravenous infusion on Days 1, 4, 8, and 11 of a 3-week cycle for 8 cycles.
Total Total of all reporting groups

Baseline Measures
    VELCADE Subcutaneous     VELCADE Intravenous     Total  
Number of Participants  
[units: participants]
  148     74     222  
Age  
[units: participants]
     
<=18 years     0     0     0  
Between 18 and 65 years     74     37     111  
>=65 years     74     37     111  
Age  
[units: years]
Mean ± Standard Deviation
  64.3  ± 8.96     64.0  ± 12.11     64.2  ± 10.09  
Gender  
[units: participants]
     
Female     74     27     101  
Male     74     47     121  
Region of Enrollment  
[units: participants]
     
France     22     14     36  
Belgium     7     5     12  
Germany     2     4     6  
Netherlands     6     4     10  
United Kingdom     6     3     9  
Ukraine     51     17     68  
Russian Federation     26     9     35  
Poland     20     7     27  
Argentina     5     8     13  
India     3     3     6  



  Outcome Measures
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1.  Primary:   Number of Patients With Overall Response (Complete Response + Partial Response)   [ Time Frame: Over 4 cycles (prior to the addition of dexamethasone) ]

Measure Type Primary
Measure Title Number of Patients With Overall Response (Complete Response + Partial Response)
Measure Description

Disease response was measured according to European Group for Blood and Marrow Transplantation (EBMT) criteria with the addition of the response categories of nCR and VGPR.

Complete response requires disappearance of monoclonal protein from the blood and urine and <5% plasma cells in the bone marrow on at least 2 determinations for a minimum of 6 weeks.

Partial Response requires ≥50% reduction in serum m-protein for at least 2 determinations at least 6 weeks apart and if present, reduction in 24-hour urinary light chain excretion by either ≥90% or to <200 mg

Time Frame Over 4 cycles (prior to the addition of dexamethasone)  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The response-evaluable population was defined as subjects who received at least 1 dose of study drug and had measurable, secretory multiple myeloma, defined as a serum monoclonal IgG or IgM of ≥10 g/L or a serum monoclonal IgA or IgE ≥5 g/L, or a serum monoclonal IgD of ≥0.5g/L, or urine M-protein of ≥200 mg/24 hours, at study entry.

Reporting Groups
  Description
VELCADE Subcutaneuous VELCADE 1.3 mg/m^2 administered by subcutaneous injection on Days 1, 4, 8, and 11 of a 3-week cycle for 8 cycles.
VELCADE Intravenous VELCADE 1.3 mg/m^2 administered by intravenous injection on Days 1, 4, 8, and 11 of a 3-week cycle for 8 cycles.

Measured Values
    VELCADE Subcutaneuous     VELCADE Intravenous  
Number of Participants Analyzed  
[units: participants]
  145     73  
Number of Patients With Overall Response (Complete Response + Partial Response)  
[units: Participants]
  61     31  


Statistical Analysis 1 for Number of Patients With Overall Response (Complete Response + Partial Response)
Groups [1] All groups
Non-Inferiority/Equivalence Test [2] Yes
Method [3] Farrrington and Manning
P Value [4] 0.00201
ORR_SQ - 0.6 ORR_IV [5] 16.8
95% Confidence Interval ( 6.1 to 27.1 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  In this trial, non-inferiority is defined as retaining 60% of the IV (active control) treatment effect as measured by ORR. The non-inferiority hypothesis can be stated as: H0: ORRSC – 0.60 ORRIV <0 vs. H1: ORRSC – 0.60 ORRIV ≥0 (non-inferiority).
[2] Details of power calculation, definition of non-inferiority margin, and other key parameters:
  Assuming ORRs are 35.5% for both SC and IV, one-sided alpha level of 0.025, and approximately 80% power, approximately 216 subjects (144 SC:72 IV) are needed to show non-inferiority of SC to IV VELCADE.
[3] Other relevant method information, such as adjustments or degrees of freedom:
  CONOR P. FARRINGTON AND GODFREY MANNING STATISTICS IN MEDICINE, VOL. 9, 1447-1454(1990).
[4] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  No text entered.
[5] Other relevant estimation information:
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2.  Secondary:   Number of Patients With Complete Response   [ Time Frame: Over 4 cycles (prior to the addition of dexamethasone) ]

Measure Type Secondary
Measure Title Number of Patients With Complete Response
Measure Description

Disease response was measured according to European Group for Blood and Marrow Transplantation (EBMT) criteria with the addition of the response categories of nCR and VGPR.

Complete response requires disappearance of monoclonal protein from the blood and urine and <5% plasma cells in the bone marrow on at least 2 determinations for a minimum of 6 weeks.

Time Frame Over 4 cycles (prior to the addition of dexamethasone)  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The response-evaluable population was defined as subjects who received at least 1 dose of study drug and had measurable, secretory multiple myeloma, defined as a serum monoclonal IgG or IgM of ≥10 g/L or a serum monoclonal IgA or IgE ≥5 g/L, or a serum monoclonal IgD of ≥0.5g/L, or urine M-protein of ≥200 mg/24 hours, at study entry.

Reporting Groups
  Description
VELCADE Subcutaneous VELCADE 1.3 mg/m^2 administered by subcutaneous injection on Days 1, 4, 8, and 11 of a 3-week cycle for 8 cycles.
VELCADE Intravenous VELCADE 1.3 mg/m^2 administered by intravenous infusion on Days 1, 4, 8, and 11 of a 3-week cycle for 8 cycles.

Measured Values
    VELCADE Subcutaneous     VELCADE Intravenous  
Number of Participants Analyzed  
[units: participants]
  145     73  
Number of Patients With Complete Response  
[units: Participants]
  9     6  

No statistical analysis provided for Number of Patients With Complete Response




  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
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Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
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