A Study to Evaluate Two Different Regimens of VELCADE in Combination With Dexamethasone, Thalidomide and Cyclophosphamide (VDT vs VDTC) in Newly Diagnosed Multiple Myeloma

January 25, 2012 updated by: Millennium Pharmaceuticals, Inc.

A Phase 2, Randomized Study of VELCADE® (Bortezomib), Dexamethasone, and Thalidomide Versus VELCADE® (Bortezomib), Dexamethasone, Thalidomide, and Cyclophosphamide in Subjects With Previously Untreated Multiple Myeloma Who Are Candidates for Autologous Transplantation

The purpose of this Phase 2 randomized study is to evaluate the efficacy and safety of treatment with a regimen of VELCADE, dexamethasone, and thalidomide (VDT) or VELCADE, dexamethasone, thalidomide, and cyclophosphamide (VDTC) in subjects with newly diagnosed symptomatic multiple myeloma who have received no prior treatment and are candidates to receive high-dose therapy and autologous bone marrow/stem cell transplantation.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

98

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Austria
      • Vienna, Austria, A-1160
        • Wilhelminenspital-1

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 70 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Male or female between ≥18 and ≤70 years
  • Patient is a candidate for HDT combined with an autologous SCT
  • Karnofsky Performance Status score of ≥60%
  • Multiple myeloma diagnosed according to the following standard criteria AND requiring systemic therapy:
  • Presence of M-component in serum and/or urine, plus clonal plasma cells in the bone marrow and/or a documented clonal plasmacytoma

  • PLUS 1 or more of the following:

    1. Calcium elevation (>11.5 mg/dL or >2.65 mmol/L)
    2. Renal insufficiency (creatinine >2 mg/dL or >177 umol/L)
    3. Anemia (hemoglobin <10 g/dL [<12.5 mmol/L] or at least 2 mg/dL [1.25 mmol/L] below normal)
    4. Bone disease (lytic lesions or osteopenia)

  • AND fulfill criteria for measurable disease, as defined by at least 1 of the following 3 measurements:

    1. Serum M-protein ≥1 g/dL (≥10 g/L)
    2. Urine M-protein ≥200 mg/24 h
    3. Serum free light chain (FLC) assay: Involved FLC level ≥10 mg/dL (≥100 mg/L) provided serum FLC ratio is abnormal
  • Women of childbearing potential must agree to use 2 methods of contraception.
  • Males must agree to use barrier contraception.
  • Subjects (or their legally acceptable representatives) must have signed an informed consent document.
  • To participate in the optional pharmacogenomic component of this study, subjects (or their legally acceptable representative) must have signed the informed consent form. Refusal to consent for this component does not exclude a subject from participation in the clinical study.

Exclusion Criteria:

  • Diagnosis of smoldering OR non-secretory multiple myeloma or monoclonal gammopathy of undetermined significance (MGUS).
  • Diagnosis of Waldenström's disease or other conditions in which IgM M-protein is present in the absence of a clonal plasma cell infiltration with lytic bone lesions.
  • Prior or current systemic therapy for multiple myeloma including steroids.
  • Radiation therapy and/or plasmapheresis within 15 days before randomization.
  • History of allergic reaction attributable to compounds being given (VELCADE, thalidomide, dexamethasone, and/or cyclophosphamide) or compounds containing boron or mannitol.
  • Peripheral neuropathy or neuropathic pain Grade 2 or higher, as defined by National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 3.0.
  • Uncontrolled or severe cardiovascular disease
  • Concurrent medical condition or disease (e.g., active systemic infection, uncontrolled diabetes) that is likely to interfere with study procedures or results, or that in the opinion of the investigator would constitute a hazard for participating in this study.
  • Use of any investigational drugs within 30 days before randomization
  • Pregnant or lactating women: A serum β-hCG pregnancy test must be performed at the Screening visit for female subjects of childbearing potential.
  • Employees of the investigator or study center, with direct involvement in the proposed study or other studies under the direction of that investigator or study center, as well as family members of the employees or the investigator.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: 1
bortezomib, dexamethasone, and thalidomide
Drug: bortezomib, dexamethasone, and thalidomide

VELCADE (bortezomib) twice weekly for 4 cycles (4 doses per cycle), prior to high-dose chemotherapy (HDT) and stem cell transplantation(SCT). Subjects will receive VELCADE 1.3 mg/m2 as an intravenous (i.v.) bolus injection on Days 1,4,8, and 11, followed by a 10 day rest period (Days 12 to 21)

Dexamethasone 40 mg/day will be given by mouth (p.o.) on Days 1-4 and Days 9-12 in each of 4 cycles.

Thalidomide will be given by mouth (p.o.)every day, starting on Day 1 of Cycle 1 (e.g. the same day of the first dose of VELCADE) and continuing until Day 21 of Cycle 4 at a dose of 100 mg/day (bedtime).
Experimental: 2
bortezomib, dexamethasone, thalidomide, and cyclophosphamide
Drug: bortezomib, dexamethasone, thalidomide, and cyclophosphamide

VELCADE (bortezomib) twice weekly for 4 cycles (4 doses per cycle), prior to high-dose chemotherapy(HDT)and stem cell transplantation(SCT). Subjects will receive VELCADE 1.3 mg/m2 as an intravenous (i.v.) bolus injection on Days 1,4,8, and 11, followed by a 10 day rest period (Days 12 to 21).

Dexamethasone 40 mg/day will be given by mouth (p.o.) on Days 1-4 and Days 9-12 in each of 4 cycles.

Thalidomide will be given by mouth (p.o.) every day, starting on Day 1 of Cycle 1 (e.g., the same day of the first dose of VELCADE) and continuing until Day 21 of Cycle 4 at a dose of 100 mg/day (bedtime).

Cyclophosphamide will be given as an intravenous (i.v.) dose of 400 mg/m2 on Day 1 and Day 8 of each 3-week cycle, for a total of 4 cycles.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Percent of Particpants Achieving Overall Combined Complete Response (CR) Following Induction
Time Frame: all data included in clinical database as of 10 April 2009

Percent of Particpants Achieving Overall combined complete response (CR w/normalized serum κ:λ ratio + CR + near complete response (nCR)) following induction therapy.

  • CR criteria: negative immunofixation on the serum and urine, disappearance of any soft tissue plasmacytomas and <5% plasma cells in bone marrow.
  • κ:λ ratio: normal free light chain (FLC) ratio
  • nCR criteria: positive immunofixation analysis of serum or urine as the only evidence of disease; disappearance of any soft tissue plasmacytomas and <5% plasma cells in bone marrow.
all data included in clinical database as of 10 April 2009

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Percent of Participants Achieving Overall Combined Complete Response (CR) Following High-dose Chemotherapy (HDT)/Stem Cell Transplantation (SCT)
Time Frame: all data included in clinical database as of 10 April 2009

Percent of Participants Achieving Overall Combined Complete Response (CR) (CR w/normalized serum κ:λ ratio + CR + Near Complete Response (nCR)) following stem cell transplantation.

  • CR criteria: negative immunofixation on the serum and urine, disappearance of any soft tissue plasmacytomas and <5% plasma cells in bone marrow.
  • κ:λ ratio: normal free light chain (FLC) ratio
  • nCR criteria: positive immunofixation analysis of serum or urine as the only evidence of disease; disappearance of any soft tissue plasmacytomas and <5% plasma cells in bone marrow.
all data included in clinical database as of 10 April 2009

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Millennium Pharmaceuticals, Inc.

Collaborators

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

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

October 1, 2007

Primary Completion (Actual)

April 1, 2009

Study Completion (Actual)

May 1, 2009

Study Registration Dates

First Submitted

September 14, 2007

First Submitted That Met QC Criteria

September 14, 2007

First Posted (Estimate)

September 18, 2007

Study Record Updates

Last Update Posted (Estimate)

January 26, 2012

Last Update Submitted That Met QC Criteria

January 25, 2012

Last Verified

January 1, 2012

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 26866138-MMY-2043

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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