Phase 1/2 Study of VELCADE® in Combination With Other Drugs to Treat Previously Untreated Multiple Myeloma Patients (EVOLUTION)

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:
NCT00507442
First received: July 25, 2007
Last updated: July 18, 2013
Last verified: April 2012
Results First Received: November 28, 2011  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Safety/Efficacy Study;   Intervention Model: Parallel Assignment;   Masking: Open Label;   Primary Purpose: Treatment
Condition: Multiple Myeloma
Interventions: Drug: VELCADE (bortezomib)
Drug: dexamethasone
Drug: cyclophosphamide
Drug: Revlimid (lenalidomide)

  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
V-DR

VELCADE (bortezomib), dexamethasone, and Revlimid (lenalidomide) Bortezomib: 1.3 mg/m^2/dose IV on Days 1, 4, 8, and 11 of a 3-week cycle for 8 cycles, then on Days 1, 8, 15, and 22 of a 6-week cycle for 4 cycles.

Dexamethasone: 40 mg orally [PO] on Days 1, 8, and 15 of a 3-week cycle for 8 cycles, then stop.

Lenalidomide: 25 mg PO on Days 1 through 14 of a 3-week cycle for 8 cycles, then stop.

VDCR

VELCADE (bortezomib), dexamethasone, cyclophosphamide, Revlimid (lenalidomide) Bortezomib: 1.3 mg/m^2/dose IV on Days 1, 4, 8, and 11 of a 3-week cycle for 8 cycles, then on Days 1, 8, 15, and 22 of a 6-week cycle for 4 cycles.

Dexamethasone: 40 mg PO on Days 1, 8, and 15 of a 3-week cycle for 8 cycles, then stop.

Cyclophosphamide: 100 - 500 mg/m^2 dose PO on Days 1 and 8 of a 3-week cycle for 8 cycles, then stop.

Lenalidomide: 15 mg PO on Days 1 through 14 of a 3-week cycle for 8 cycles, then stop.

V-DC

VELCADE (bortezomib), dexamethasone, cyclophosphamide Bortezomib: 1.3 mg/m^2/dose IV on Days 1, 4, 8, and 11 of a 3-week cycle for 8 cycles, then on Days 1, 8, 15, and 22 of a 6-week cycle for 4 cycles.

Dexamethasone: 40 mg orally PO on Days 1, 8, and 15 of a 3-week cycle for 8 cycles, then stop.

Cyclophosphamide: 500 mg/m^2 dose PO on Days 1 and 8 of a 3-week cycle for 8 cycles, then stop.

VDC-mod

Modified dosing of VELCADE (bortezomib), dexamethasone, cyclophosphamide Bortezomib: 1.3 mg/m^2/dose IV on Days 1, 4, 8, and 11 of a 3-week cycle for 8 cycles, then on Days 1, 8, 15, and 22 of a 6-week cycle for 4 cycles.

Dexamethasone: 40 mg PO on Days 1, 8, and 15 of a 3-week cycle for 8 cycles, then stop.

Cyclophosphamide: 500 mg/m^2 dose PO on Days 1, 8, and 15 of a 3-week cycle for 8 cycles, then stop.


Participant Flow:   Overall Study
    V-DR     VDCR     V-DC     VDC-mod  
STARTED     42     66     33     17  
COMPLETED     26     39     18     12  
NOT COMPLETED     16     27     15     5  
Adverse Event                 8                 11                 4                 1  
Protocol Violation                 0                 1                 0                 0  
Lost to Follow-up                 0                 0                 1                 0  
Physician Decision                 0                 2                 4                 1  
Progressive Disease                 2                 4                 2                 0  
Withdrawal by Subject                 4                 4                 2                 1  
Not Specified                 2                 5                 2                 2  



  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
V-DR

VELCADE (bortezomib), dexamethasone, and Revlimid (lenalidomide) Bortezomib: 1.3 mg/m^2/dose IV on Days 1, 4, 8, and 11 of a 3-week cycle for 8 cycles, then on Days 1, 8, 15, and 22 of a 6-week cycle for 4 cycles.

Dexamethasone: 40 mg orally [PO] on Days 1, 8, and 15 of a 3-week cycle for 8 cycles, then stop.

Lenalidomide: 25 mg PO on Days 1 through 14 of a 3-week cycle for 8 cycles, then stop.

VDCR

VELCADE (bortezomib), dexamethasone, cyclophosphamide, Revlimid (lenalidomide) Bortezomib: 1.3 mg/m^2/dose IV on Days 1, 4, 8, and 11 of a 3-week cycle for 8 cycles, then on Days 1, 8, 15, and 22 of a 6-week cycle for 4 cycles.

Dexamethasone: 40 mg PO on Days 1, 8, and 15 of a 3-week cycle for 8 cycles, then stop.

Cyclophosphamide: 100 - 500 mg/m^2 dose PO on Days 1 and 8 of a 3-week cycle for 8 cycles, then stop.

Lenalidomide: 15 mg PO on Days 1 through 14 of a 3-week cycle for 8 cycles, then stop.

V-DC

VELCADE (bortezomib), dexamethasone, cyclophosphamide Bortezomib: 1.3 mg/m^2/dose IV on Days 1, 4, 8, and 11 of a 3-week cycle for 8 cycles, then on Days 1, 8, 15, and 22 of a 6-week cycle for 4 cycles.

Dexamethasone: 40 mg orally PO on Days 1, 8, and 15 of a 3-week cycle for 8 cycles, then stop.

Cyclophosphamide: 500 mg/m^2 dose PO on Days 1 and 8 of a 3-week cycle for 8 cycles, then stop.

VDC-mod

Modified dosing of VELCADE (bortezomib), dexamethasone, cyclophosphamide Bortezomib: 1.3 mg/m^2/dose IV on Days 1, 4, 8, and 11 of a 3-week cycle for 8 cycles, then on Days 1, 8, 15, and 22 of a 6-week cycle for 4 cycles.

Dexamethasone: 40 mg PO on Days 1, 8, and 15 of a 3-week cycle for 8 cycles, then stop.

Cyclophosphamide: 500 mg/m^2 dose PO on Days 1, 8, and 15 of a 3-week cycle for 8 cycles, then stop.

Total Total of all reporting groups

Baseline Measures
    V-DR     VDCR     V-DC     VDC-mod     Total  
Number of Participants  
[units: participants]
  42     66     33     17     158  
Age  
[units: participants]
         
<=18 years     0     0     0     0     0  
Between 18 and 65 years     27     42     21     11     101  
>=65 years     15     24     12     6     57  
Age  
[units: years]
Mean ± Standard Deviation
  59.5  ± 8.76     60.9  ± 8.97     61.4  ± 8.32     59.6  ± 9.16     60.5  ± 8.75  
Gender  
[units: participants]
         
Female     18     28     14     10     70  
Male     24     38     19     7     88  
Region of Enrollment  
[units: participants]
         
United States     42     66     33     17     158  



  Outcome Measures
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1.  Primary:   Number of Patients With Combined Complete Response and Very Good Partial Response   [ Time Frame: Up to 48 weeks or until disease progression ]

2.  Secondary:   Number of Patients With Adverse Events (AEs)   [ Time Frame: From first dose of study drug through the 30 day post-treatment AE assessment visit ]

3.  Secondary:   Number of Patients With Overall Response   [ Time Frame: Up to 48 weeks or until disease progression ]

4.  Secondary:   Number of Patients With Stringent Complete Response Rate   [ Time Frame: Up to 48 weeks or until disease progression ]

5.  Secondary:   Number of Patients With Complete Response Rate + Near Complete Response Rate   [ Time Frame: Up to 48 weeks or until disease progression ]

6.  Secondary:   Duration of Response   [ Time Frame: Up to 48 weeks or until disease progression ]

7.  Secondary:   Time to Disease Progression   [ Time Frame: Up to 48 weeks or until disease progression ]

8.  Secondary:   Time to Response   [ Time Frame: Up to 48 weeks or until disease response ]

9.  Secondary:   Progression-free Survival   [ Time Frame: Up to 48 weeks or until disease progression/death ]

10.  Secondary:   Probability of 1-year Survival   [ Time Frame: survival probability at 1 year after randomization ]

11.  Secondary:   Overall Survival   [ Time Frame: Up to 48 weeks or until death ]


  Serious Adverse Events


  Other Adverse Events


  More Information
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Certain Agreements:  
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.


Limitations and Caveats
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
No text entered.  


Results Point of Contact:  
Name/Title: Dixie-Lee Esseltine, MD
Organization: Millennium Pharmaceuticals, Inc
phone: (617) 679-7000


No publications provided by Millennium Pharmaceuticals, Inc.

Publications automatically indexed to this study:

Responsible Party: Millennium Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier: NCT00507442     History of Changes
Other Study ID Numbers: C05008
Study First Received: July 25, 2007
Results First Received: November 28, 2011
Last Updated: July 18, 2013
Health Authority: United States: Food and Drug Administration