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
  Purpose

The purpose of this Phase 1/2 study is to evaluate the efficacy and safety of treatment with VELCADE, dexamethasone, and Revlimid® (VDR) as well as VELCADE, dexamethasone, cyclophosphamide, and Revlimid (VDCR) in patients with multiple myeloma who have received no prior treatment. This study will evaluate whether the addition of Revlimid to VELCADE and Dexamethasone will increase the complete response (CR)/ very good partial response (VGPR) rate.


Condition Intervention Phase
Multiple Myeloma
Drug: VELCADE (bortezomib)
Drug: dexamethasone
Drug: cyclophosphamide
Drug: Revlimid (lenalidomide)
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase 1/2 Study of VELCADE® (Bortezomib), Dexamethasone, and Revlimid® (Lenalidomide) Versus VELCADE, Dexamethasone, Cyclophosphamide, and Revlimid Versus VELCADE, Dexamethasone and Cyclophosphamide in Subjects With Previously Untreated Multiple Myeloma

Resource links provided by NLM:


Further study details as provided by Millennium Pharmaceuticals, Inc.:

Primary Outcome Measures:
  • Number of Patients With Combined Complete Response and Very Good Partial Response [ Time Frame: Up to 48 weeks or until disease progression ] [ Designated as safety issue: No ]

    Complete response requires negative immunofixation on the serum and urine and disappearance of any soft tissue plasmacytomas and < 5% plasma cells in bone marrow.

    Very good partial response requires serum and urine M-protein detectable by immunofixation but not on electrophoresis or 90% or greater reduction in serum M-protein plus urine M-protein level < 100 mg per 24 h



Secondary Outcome Measures:
  • Number of Patients With Adverse Events (AEs) [ Time Frame: From first dose of study drug through the 30 day post-treatment AE assessment visit ] [ Designated as safety issue: Yes ]
    Evaluate the safety and tolerability of the combination therapy

  • Number of Patients With Overall Response [ Time Frame: Up to 48 weeks or until disease progression ] [ Designated as safety issue: No ]

    Overall Response includes complete response and partial response.

    Complete response requires negative immunofixation on the serum and urine and disappearance of any soft tissue plasmacytomas and < 5% plasma cells in bone marrow.

    Partial response requires at least 50% reduction of serum M-protein and reduction in 24-h urinary M-protein by at least 90% or to < 200 mg per 24 hour.


  • Number of Patients With Stringent Complete Response Rate [ Time Frame: Up to 48 weeks or until disease progression ] [ Designated as safety issue: No ]
    Stringent Complete Response is defined as complete response plus normal free light chain (kappa/lambda) ratio and absence of clonal cells in bone marrow by immunohistochemistry or immunofluorescence.

  • Number of Patients With Complete Response Rate + Near Complete Response Rate [ Time Frame: Up to 48 weeks or until disease progression ] [ Designated as safety issue: No ]

    Complete response requires negative immunofixation on the serum and urine and disappearance of any soft tissue plasmacytomas and < 5% plasma cells in bone marrow.

    Near Complete response requires positive immunofixation on the serum and/or urine and disappearance of any soft tissue plasmacytomas and < 5% plasma cells in bone marrow.


  • Duration of Response [ Time Frame: Up to 48 weeks or until disease progression ] [ Designated as safety issue: No ]

    Duration of response is the time from date of first documented confirmed response to date of first documented progressive disease. A confirmed response is a response that has been observed on at least two consecutive assessments.

    Disease progression requires any one or more of the following: serum m-protein increase >= 25% from nadir(absolute increase >= 0.5 g/dL); Urine m-protein increase >= 25% from nadir(absolute increase >= 200 mg/24 hr), bone marrow plasma cell percentage increase >= 25% from nadir(absolute increase >= 10%), new bone lesion or soft tissue plasmacytomas.


  • Time to Disease Progression [ Time Frame: Up to 48 weeks or until disease progression ] [ Designated as safety issue: No ]

    Time to disease progression is defined as time from the date of randomization to the date of first documented progressive disease.

    Disease progression requires any one or more of the following: serum m-protein increase >= 25% from nadir(absolute increase >= 0.5 g/dL); Urine m-protein increase >= 25% from nadir(absolute increase >= 200 mg/24 hr), bone marrow plasma cell percentage increase >= 25% from nadir(absolute increase >= 10%), new bone lesion or soft tissue plasmacytomas.


  • Time to Response [ Time Frame: Up to 48 weeks or until disease response ] [ Designated as safety issue: No ]
    Time to response is defined as time from date of randomization to the date of the first documentation of a confirmed response. confirmed response is a response that has been observed on at least two consecutive assessments.

  • Progression-free Survival [ Time Frame: Up to 48 weeks or until disease progression/death ] [ Designated as safety issue: No ]

    Progression-free survival is defined as time from the date of randomization to the date of the first documented progressive disease or death.

    Disease progression requires any one or more of the following: serum m-protein increase >= 25% from nadir(absolute increase >= 0.5 g/dL); Urine m-protein increase >= 25% from nadir(absolute increase >= 200 mg/24 hr), bone marrow plasma cell percentage increase >= 25% from nadir(absolute increase >= 10%), new bone lesion or soft tissue plasmacytomas.


  • Probability of 1-year Survival [ Time Frame: survival probability at 1 year after randomization ] [ Designated as safety issue: No ]
  • Overall Survival [ Time Frame: Up to 48 weeks or until death ] [ Designated as safety issue: No ]
    Overall survival is defined as time from the date of randomization to the date of death


Enrollment: 158
Study Start Date: August 2007
Study Completion Date: November 2010
Primary Completion Date: October 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: VDR
VELCADE (bortezomib), dexamethasone, and Revlimid (lenalidomide)
Drug: VELCADE (bortezomib)
bortezomib 1.3 mg/m^2 given via 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 (maintenance).
Drug: dexamethasone
dexamethasone 40 mg orally on days 1, 8, and 15 of a 3-week cycle for 8 cycles, then stop
Drug: Revlimid (lenalidomide)

lenalidomide 25 mg orally on days 1 to 14 of a 3-week cycle for 8 cycles then stop (VDR arm)

lenalidomide 15 mg orally on days 1 to 14 of a 3-week cycle for 8 cycles then stop (VDCR arm)

Experimental: VDCR
VELCADE (bortezomib), dexamethasone, cyclophosphamide, Revlimid (lenalidomide)
Drug: VELCADE (bortezomib)
bortezomib 1.3 mg/m^2 given via 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 (maintenance).
Drug: dexamethasone
dexamethasone 40 mg orally on days 1, 8, and 15 of a 3-week cycle for 8 cycles, then stop
Drug: cyclophosphamide
cyclophosphamide 500 mg/m^2 orally on days 1 and 8 of a 3-week cycle for 8 cycles, then stop
Drug: Revlimid (lenalidomide)

lenalidomide 25 mg orally on days 1 to 14 of a 3-week cycle for 8 cycles then stop (VDR arm)

lenalidomide 15 mg orally on days 1 to 14 of a 3-week cycle for 8 cycles then stop (VDCR arm)

Experimental: VDC
VELCADE (bortezomib), dexamethasone, cyclophosphamide
Drug: VELCADE (bortezomib)
bortezomib 1.3 mg/m^2 given via 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 (maintenance).
Drug: dexamethasone
dexamethasone 40 mg orally on days 1, 8, and 15 of a 3-week cycle for 8 cycles, then stop
Drug: cyclophosphamide
cyclophosphamide 500 mg/m^2 orally on days 1 and 8 of a 3-week cycle for 8 cycles, then stop
Experimental: VDC-mod
Modified dosing of VELCADE (bortezomib), dexamethasone, cyclophosphamide
Drug: VELCADE (bortezomib)
bortezomib 1.3 mg/m^2 given via 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 (maintenance).
Drug: dexamethasone
dexamethasone 40 mg orally on days 1, 8, and 15 of a 3-week cycle for 8 cycles, then stop
Drug: cyclophosphamide
cyclophosphamide 500 mg/m^2 orally on days 1 and 8 of a 3-week cycle for 8 cycles, then stop

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Voluntary written informed consent
  • Male or female subject 18 years of age or older
  • A Karnofsky Performance Status score of ≥50% (Eastern Cooperative Oncology Group Performance Status score ≤2)
  • Subjects must have symptomatic myeloma or asymptomatic myeloma with myeloma-related organ damage
  • Diagnosed Multiple myeloma
  • Subjects must have measurable disease requiring systemic therapy
  • Subjects must not have been treated previously with any systemic therapy for multiple myeloma
  • Two weeks must have elapsed since the date of the last radiotherapy treatment
  • Women of childbearing potential must have a negative serum or urine pregnancy test with a sensitivity of at least 50 mIU/mL within 10 to 14 days prior to therapy and repeated within 24 hours before starting study drug. They must commit to continued abstinence from heterosexual intercourse or begin 2 acceptable methods of birth control (1 highly effective method and 1 additional effective method) used at the same time, beginning at least 4 weeks before initiation of Revlimid treatment. Women must also agree to ongoing pregnancy testing
  • Men must agree to not father a child and agree to use a latex condom during therapy and for 4 weeks after the last dose of study drug, even if they have had a successful vasectomy, if their partner is of childbearing potential
  • All subjects must agree to comply with the requirements of the RevAssistSM program

Exclusion Criteria:

  • History of allergy to any of the study medications, their analogues, or excipients in the various formulations
  • ≥Grade 2 peripheral neuropathy on clinical examination
  • Myocardial infarction within 6 months prior to enrollment or New York Heart Association Class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or clinically significant conduction system abnormalities.
  • Female subject who is pregnant or breast-feeding
  • Clinically relevant active infection or serious comorbid medical conditions
  • Any condition, including laboratory abnormalities, that in the opinion of the Investigator places the subject at unacceptable risk if he/she were to participate in the study. This includes but is not limited to serious medical or psychiatric illness likely to interfere with participation in this clinical study
  • Active prior malignancy diagnosed or treated within the last 3 years
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00507442

Locations
United States, Colorado
Rocky Mountain Cancer Center
Denver, Colorado, United States, 80218
United States, Minnesota
Mayo Clinic
Rochester, Minnesota, United States, 55904-0001
Sponsors and Collaborators
Millennium Pharmaceuticals, Inc.
Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
Investigators
Study Director: Medical Monitor Millennium Pharmaceuticals, Inc.
  More Information

No publications provided by Millennium Pharmaceuticals, Inc.

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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

Keywords provided by Millennium Pharmaceuticals, Inc.:
Treatment for patients with multiple myeloma
who have received no prior treatment

Additional relevant MeSH terms:
Multiple Myeloma
Neoplasms, Plasma Cell
Neoplasms by Histologic Type
Neoplasms
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Paraproteinemias
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Lymphoproliferative Disorders
Immunoproliferative Disorders
Immune System Diseases
Cyclophosphamide
Thalidomide
Bortezomib
Lenalidomide
Dexamethasone
Dexamethasone acetate
Dexamethasone 21-phosphate
BB 1101
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antirheumatic Agents
Therapeutic Uses
Antineoplastic Agents, Alkylating
Alkylating Agents

ClinicalTrials.gov processed this record on July 29, 2014