Randomized Phase 3b Study in Previously Untreated Multiple Myeloma Patients: VELCADE,Thalidomide, and Dexamethasone Versus VELCADE and Dexamethasone Versus VELCADE, Melphalan, and Prednisone (UPFRONT)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Millennium Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier:
NCT00507416
First received: July 25, 2007
Last updated: July 1, 2013
Last verified: July 2013
  Purpose

This is a randomized, open label, multicenter clinical trial to compare the efficacy and safety of VELCADE dexamethasone versus VELCADE, thalidomide, and dexamethasone versus VELCADE, melphalan, and prednisone in patients with previously untreated multiple myeloma who are not considered candidates for high-dose chemotherapy and autologous stem cell transplantation. This study will consist of a Screening period (generally 4 weeks or less), an Induction Treatment period (approximately 6 months), a Maintenance Treatment period (approximately 6 months), and a Post-treatment period.


Condition Intervention Phase
Multiple Myeloma
Drug: bortezomib, thalidomide, and dexamethasone (VTD)
Drug: bortezomib and dexamethasone (VD)
Drug: bortezomib, melphalan and prednisone (VMP)
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Randomized Phase 3b Study of Three Treatment Regimens in Subjects With Previously Untreated Multiple Myeloma Who Are Not Considered Candidates for High-Dose Chemotherapy and Autologous Stem Cell Transplantation: VELCADE,Thalidomide, and Dexamethasone Versus VELCADE and Dexamethasone Versus VELCADE, Melphalan, and Prednisone

Resource links provided by NLM:


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

Primary Outcome Measures:
  • Progression Free Survival. [ Time Frame: Up to 3 years after treatment is completed ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • - Overall response rate - Overall survival - Time to alternative therapy [ Time Frame: Up to 3 years after treatment is completed ] [ Designated as safety issue: No ]

Enrollment: 502
Study Start Date: June 2007
Study Completion Date: April 2013
Primary Completion Date: March 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Bortezomib, Thalidomide, and Dexamethasone (VTD) Drug: bortezomib, thalidomide, and dexamethasone (VTD)

bortezomib intravenously on Days 1, 4, 8, and 11 of each 21-day cycle during Cycles 1-8.

Thalidomide orally on Days 1-21 of a 21-day cycle during Cycles 1-8.

Dexamethasone orally once daily (QD) on Days 1, 2, 4, 5, 8, 9, 11, and 12 of each 21-day cycle during Cycles 1-4 (ie, on the day of and day after bortezomib administration), and then orally QD on Days 1, 2, 4, and 5 of a 21-day cycle during Cycles 5-8

Dosing Schedule for the Maintenance Treatment Periods (Cycles 9 though 13) All subjects will receive bortezomib intravenously on Days 1, 8, 15, and 22 of a 35-day cycle during Cycles 9-13.

Other Name: VELCADE
Experimental: Bortezomib and Dexamethasone (VD) Drug: bortezomib and dexamethasone (VD)

bortezomib intravenously on Days 1, 4, 8, and 11 of each 21-day cycle during Cycles 1-8.

Dexamethasone orally once daily (QD) on Days 1, 2, 4, 5, 8, 9, 11, and 12 of each 21-day cycle during Cycles 1-4 (ie, on the day of and day after bortezomib administration), and then orally QD on Days 1, 2, 4, and 5 of a 21-day cycle during Cycles 5-8.

Dosing Schedule for the Maintenance Treatment Periods (Cycles 9 though 13) All subjects will receive bortezomib intravenously on Days 1, 8, 15, and 22 of a 35-day cycle during Cycles 9-13.

Other Name: VELCADE
Experimental: Bortezomib, melphalan, and prednisone (VMP) Drug: bortezomib, melphalan and prednisone (VMP)

bortezomib administered intravenously on Days 1, 4, 8, and 11 of each 21-day cycle during Cycles 1-8.

Melphalan: orally once daily (QD) on Days 1-4 every other cycle during Cycles 1-8.

Prednisone:orally QD on Days 1-4 every other cycle during Cycles 1-8.

Dosing Schedule for the Maintenance Treatment Periods (Cycles 9 though 13) All subjects will receive bortezomib intravenously on Days 1, 8, 15, and 22 of a 35-day cycle during Cycles 9-13.

Other Name: VELCADE

  Eligibility

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

Inclusion Criteria:

  • Male or female subjects 18 years of age or older
  • Subject is not a candidate for high-dose chemotherapy and stem cell transplantation(HDT/SCT) due to age, presence of important comorbid condition(s) likely to have a negative impact on tolerability of HDT-SCT, or subject preference.
  • A Karnofsky Performance Status score of ≥50%
  • Symptomatic multiple myeloma or asymptomatic multiple myeloma with related organ or tissue damage.
  • Asymptomatic multiple myeloma-related organ or tissue damage can include presence of an asymptomatic lytic bone lesion or plasmacytoma, the presence of anemia(hemoglobin <10 g/dL), renal function impairment (serum creatinine > upper limit of normal [ULN]) or hypercalcemia (serum calcium >ULN).
  • Subject must have measurable disease requiring systemic therapy. Measurable disease is defined by at least 1 of the following criteria:
  • quantifiable serum M-protein value (>1 g/dL of IgG or IgM M-protein, >0.5g/dL of IgA M-protein, >0.5 g/dL of IgD M-protein)
  • urine light-chain excretion ≥200 mg/24 hours
  • Voluntary written informed consent must be given before performance of any study related procedure not part of normal medical care, with the understanding that consent may be withdrawn by the subject at any time without prejudice to future medical care.

Exclusion Criteria:

  • Diagnosis of smoldering multiple myeloma or MGUS. Smoldering multiple myeloma is defined as asymptomatic multiple myeloma with absence of lytic bone lesions. MGUS is defined by presence of serum monoclonal protein <3 g/dL; absence of lytic bone lesions, anemia, hypercalcemia, and renal insufficiency related to the monoclonal protein; and (if determined) proportion of plasma cells in the bone marrow of 10% or less.
  • Diagnosis of Waldenström's disease or other conditions in which IgM M-protein is present in the absence of a clonal plasma cell infiltration or lytic bone lesions.
  • Previously or currently treated with any systemic therapy for multiple myeloma. Prior treatment of hypercalcemia or spinal cord compression with corticosteroids or radiation therapy, respectively, does not disqualify the subject (the dose of corticosteroids should not exceed the equivalent of 160 mg of dexamethasone in 2-week period).
  • Radiation therapy within 2 weeks before randomization. Enrollment of subjects who require concurrent radiotherapy (which must be localized in its field size) should be deferred until the radiotherapy is completed and 2 weeks have elapsed since the last date of therapy.
  • Major surgery within 30 days before randomization (Kyphoplasty is not considered major surgery)
  • History of allergy to any of the study medications, their analogues, or excipients in the various formulations
  • ≥Grade 2 peripheral neuropathy on clinical examination within 21 days before enrollment.
  • Any of the following clinical laboratory values within 21 days prior to enrollment:
  • Absolute neutrophil count (ANC) <1000 cells/mm3
  • Platelets <100,000 × 109/L, or <70 × 109/L if thrombocytopenia is considered by the investigator to be due to myeloma infiltration of bone marrow
  • Aspartate aminotransferase (AST [SGOT]) or alanine aminotransferase (ALT [SGPT]) >2× the ULN
  • Serum creatinine >2 mg/dL (>176.8µmol/L); if the rise in creatinine is related to myeloma and there has been demonstrated a response to hydration, the subject may be enrolled.
  • Myocardial infarction within 6 months prior to enrollment or New York Hospital Association Class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or significant conduction system abnormalities in the opinion of the investigator. Prior to study entry, any abnormality on electrocardiogram at screening must be determined and documented by the investigator as not medically relevant.
  • 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 conditions or psychiatric illness likely to interfere with participation in this clinical study.
  • Prior malignancy except for adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, in situ breast cancer, in situ prostate cancer, or other cancer for which the subject has been disease-free for at least 3 years.
  • Female subject who is pregnant or breastfeeding. Female subjects of childbearing potential must have a negative pregnancy test with a sensitivity of at least 50 mIU/mL during Screening.
  • Use of any investigational drugs within 30 days before randomization.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00507416

  Show 235 Study Locations
Sponsors and Collaborators
Millennium Pharmaceuticals, Inc.
Investigators
Study Director: Medical Monitor Millennium Pharmaceuticals, Inc.
  More Information

Additional Information:
No publications provided

Responsible Party: Millennium Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier: NCT00507416     History of Changes
Other Study ID Numbers: C05009
Study First Received: July 25, 2007
Last Updated: July 1, 2013
Health Authority: United States: Institutional Review Board

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
Dexamethasone acetate
Dexamethasone
Prednisone
Dexamethasone 21-phosphate
Bortezomib
Melphalan
Thalidomide
BB 1101
Anti-Inflammatory Agents
Therapeutic Uses
Pharmacologic Actions
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Central Nervous System Agents

ClinicalTrials.gov processed this record on April 17, 2014