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

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:
NCT00531453
First received: September 14, 2007
Last updated: January 25, 2012
Last verified: January 2012
  Purpose

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.


Condition Intervention Phase
Multiple Myeloma
Drug: bortezomib, dexamethasone, and thalidomide
Drug: bortezomib, dexamethasone, thalidomide, and cyclophosphamide
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: 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

Resource links provided by NLM:


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

Primary Outcome Measures:
  • Percent of Particpants Achieving Overall Combined Complete Response (CR) Following Induction [ Time Frame: all data included in clinical database as of 10 April 2009 ] [ Designated as safety issue: No ]

    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.


Secondary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]

    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.


Enrollment: 98
Study Start Date: October 2007
Study Completion Date: May 2009
Primary Completion Date: April 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.


  Eligibility

Ages Eligible for Study:   18 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  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: NCT00531453

Locations
Austria
Wilhelminenspital-1
Vienna, Austria, A-1160
Sponsors and Collaborators
Millennium Pharmaceuticals, Inc.
Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
Investigators
Study Director: Medical Monitor Millennium Pharmaceuticals, Inc.
  More Information

Publications:
Ludwig H; Viterbo L; Greil R; Masszi T; Spicka I; Shpilberg O; Hajek R; Dmoszynska A; Cakana A; Enny C; Feng H; van de Velde H; and Harousseau J-L. Bortezomib, Thalidomide, and Dexamethasone (VTD) Versus VTD Plus Cyclophosphamide as Induction Therapy in Previously Untreated Multiple Myeloma Patients Eligible for HDT-ASCT: A Randomized Phase 2 Trial. Blood (ASH Annual Meeting Abstracts), Nov 2009; 114: 2312.

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Millennium Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier: NCT00531453     History of Changes
Other Study ID Numbers: 26866138-MMY-2043
Study First Received: September 14, 2007
Results First Received: April 9, 2010
Last Updated: January 25, 2012
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Multiple Myeloma
Neoplasms, Plasma Cell
Blood Protein Disorders
Cardiovascular Diseases
Hematologic Diseases
Hemorrhagic Disorders
Hemostatic Disorders
Immune System Diseases
Immunoproliferative Disorders
Lymphoproliferative Disorders
Neoplasms
Neoplasms by Histologic Type
Paraproteinemias
Vascular Diseases
BB 1101
Bortezomib
Cyclophosphamide
Dexamethasone
Dexamethasone 21-phosphate
Dexamethasone acetate
Thalidomide
Alkylating Agents
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Anti-Bacterial Agents
Anti-Infective Agents
Anti-Inflammatory Agents
Antiemetics
Antineoplastic Agents
Antineoplastic Agents, Alkylating

ClinicalTrials.gov processed this record on October 23, 2014