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Multiple MyelomaPhase 1/2EVOLUTIONNCT00507442

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

A Phase 1/2 study testing VELCADE (bortezomib), dexamethasone and cyclophosphamide in people with Multiple Myeloma, run by Millennium Pharmaceuticals, Inc. at 2 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Multiple Myeloma
What is being tested?
VELCADE (bortezomib), dexamethasone and cyclophosphamide
Could I receive a placebo?
No, everyone receives an active treatment
How many people
158 participants
Where
2 sitesUnited States
Study dates
Aug 2007to Nov 2010
Phase
Phase 1/2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
Show all 11Show fewer
  • 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

Who cannot join

  • 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

Trial locations and contacts

2 sites in 1 country.

United States2 sites

  • Rocky Mountain Cancer Center

    Denver, Colorado, 80218

  • Mayo Clinic

    Rochester, Minnesota, 55904-0001

Other trials in United States

About this study

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

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.

Being tested
VELCADE (bortezomib), dexamethasone, cyclophosphamide, Revlimid (lenalidomide)
Keywords
Treatment for patients with multiple myeloma, who have received no prior treatment
Medical subject headings
Multiple Myeloma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • 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).

  • dexamethasoneDrug

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

  • cyclophosphamideDrug

    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)

Study groups in NCT00507442
Study groupRoleWhat they receive
VDRExperimentalVELCADE (bortezomib), dexamethasone, and Revlimid (lenalidomide)
Receives: Drug: VELCADE (bortezomib); Drug: dexamethasone; Drug: Revlimid (lenalidomide)
VDCRExperimentalVELCADE (bortezomib), dexamethasone, cyclophosphamide, Revlimid (lenalidomide)
Receives: Drug: VELCADE (bortezomib); Drug: dexamethasone; Drug: cyclophosphamide; Drug: Revlimid (lenalidomide)
VDCExperimentalVELCADE (bortezomib), dexamethasone, cyclophosphamide
Receives: Drug: VELCADE (bortezomib); Drug: dexamethasone; Drug: cyclophosphamide
VDC-modExperimentalModified dosing of VELCADE (bortezomib), dexamethasone, cyclophosphamide
Receives: Drug: VELCADE (bortezomib); Drug: dexamethasone; Drug: cyclophosphamide

What is being measured

The primary outcome is the main question the study is designed to answer.

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

    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

    Measured: Up to 48 weeks or until disease progression

Secondary outcomes (10)

  1. Number of Patients With Adverse Events (AEs)

    Evaluate the safety and tolerability of the combination therapy

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

  2. Number of Patients With Overall Response

    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.

    Measured: Up to 48 weeks or until disease progression

  3. Number of Patients With Stringent Complete Response Rate

    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.

    Measured: Up to 48 weeks or until disease progression

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

    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.

    Measured: Up to 48 weeks or until disease progression

  5. Duration of Response

    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.

    Measured: Up to 48 weeks or until disease progression

  6. Time to 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.

    Measured: Up to 48 weeks or until disease progression

  7. Time to 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.

    Measured: Up to 48 weeks or until disease response

  8. Progression-free Survival

    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.

    Measured: Up to 48 weeks or until disease progression/death

  9. Probability of 1-year Survival

    Measured: survival probability at 1 year after randomization

  10. Overall Survival

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

    Measured: Up to 48 weeks or until death

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted26 Jul 2007 (estimated)
  2. Study startAug 2007
  3. Primary completionOct 2010
  4. Study completionNov 2010

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
158 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00507442
Sponsor's protocol ID
C05008
Acronym
EVOLUTION
Status last verified
Apr 2012
First submitted
25 Jul 2007
Last updated
26 Jul 2013
Data monitoring committee
No

Publications

  • Kumar S, Flinn I, Richardson PG, Hari P, Callander N, Noga SJ, Stewart AK, Turturro F, Rifkin R, Wolf J, Estevam J, Mulligan G, Shi H, Webb IJ, Rajkumar SV. Randomized, multicenter, phase 2 study (EVOLUTION) of combinations of bortezomib, dexamethasone, cyclophosphamide, and lenalidomide in previously untreated multiple myeloma. Blood. 2012 May 10;119(19):4375-82. doi: 10.1182/blood-2011-11-395749. Epub 2012 Mar 15.

    PubMed 22422823

  • Kumar SK, Flinn I, Noga SJ, Hari P, Rifkin R, Callander N, Bhandari M, Wolf JL, Gasparetto C, Krishnan A, Grosman D, Glass J, Sahovic EA, Shi H, Webb IJ, Richardson PG, Rajkumar SV. Bortezomib, dexamethasone, cyclophosphamide and lenalidomide combination for newly diagnosed multiple myeloma: phase 1 results from the multicenter EVOLUTION study. Leukemia. 2010 Jul;24(7):1350-6. doi: 10.1038/leu.2010.116. Epub 2010 May 27.

    PubMed 20508619

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing VELCADE (bortezomib), dexamethasone and cyclophosphamide in people with Multiple Myeloma, run by Millennium Pharmaceuticals, Inc. at 2 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 11 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 26 Jul 2013. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 29 Dec 2011). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of Patients With Combined Complete Response and Very Good Partial Response (time frame: Up to 48 weeks or until disease progression). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00507442, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 Jul 2013.

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