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Completed

NCT Number: NCT00507442

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

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.

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Key information

Conditions

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

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1 / Phase 2

Primary location

Rocky Mountain Cancer Center, Denver, Colorado, United States

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Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

Velcade (Bortezomib)

Drug

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).

Dexamethasone

Drug

dexamethasone 40 mg orally on days 1, 8, and 15 of a 3-week cycle for 8 cycles, then stop

Cyclophosphamide

Drug

cyclophosphamide 500 mg/m^2 orally on days 1 and 8 of a 3-week cycle for 8 cycles, then stop

Revlimid (Lenalidomide)

Drug

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)

Primary outcomes

  1. Number of Patients With Combined Complete Response and Very Good Partial Response

    Time frame: Up to 48 weeks or until disease progression

    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 outcomes

  1. Number of Patients With Adverse Events (AEs)

    Time frame: From first dose of study drug through the 30 day post-treatment AE assessment visit

    Evaluate the safety and tolerability of the combination therapy

  2. Number of Patients With Overall Response

    Time frame: Up to 48 weeks or until disease progression

    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.

  3. Number of Patients With Stringent Complete Response Rate

    Time frame: Up to 48 weeks or until disease progression

    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.

  4. Number of Patients With Complete Response Rate + Near Complete Response Rate

    Time frame: Up to 48 weeks or until disease progression

    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.

  5. Duration of Response

    Time frame: Up to 48 weeks or until disease progression

    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.

  6. Time to Disease Progression

    Time frame: Up to 48 weeks or until disease progression

    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.

  7. Time to Response

    Time frame: Up to 48 weeks or until disease response

    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.

  8. Progression-free Survival

    Time frame: Up to 48 weeks or until disease progression/death

    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.

  9. Probability of 1-year Survival

    Time frame: survival probability at 1 year after randomization

  10. Overall Survival

    Time frame: Up to 48 weeks or until death

    Overall survival is defined as time from the date of randomization to the date of death

Sponsors and collaborators

Lead sponsor

Millennium Pharmaceuticals, Inc.

Industry

Collaborators

  • Johnson & Johnson Pharmaceutical Research & Development, L.L.C.

Registry information

Official study 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

Acronym: EVOLUTION

Important dates

Study start
2007
Primary completion
2010
Study completion
2010
First posted
Jul 26, 2007
Registry last updated
Jul 26, 2013

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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