Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outcomes
Outline
Published Results
Trial Contact Information
Related Information
Registry Information

Alternate Title

Bortezomib and Dexamethasone With or Without Lenalidomide in Treating Patients With Multiple Myeloma Previously Treated With Dexamethasone

Basic Trial Information

Special Category: CTSU trial, NCI Web site featured trial

Objectives

Primary

1. To compare the progression-free survival (PFS) of patients with previously treated symptomatic multiple myeloma treated with consolidation therapy comprising bortezomib and dexamethasone with vs without lenalidomide.

Secondary

1. To determine the incremental ability of these regimens in attaining a complete response or a very good partial response (VGPR) in these patients.
2. To compare the overall survival of patients treated with these regimens.
3. To compare the toxicity of these regimens in these patients.
4. To compare the quality of life of these patients.
5. To examine the impact of differential treatment response, if observed, on quality of life of these patients.
6. To obtain prospective data on multiple myeloma specific quality of life attributes.

Entry Criteria

Disease Characteristics:

• Diagnosis of symptomatic multiple myeloma

• Must meet the following criteria at one point in the course of the disease for the original diagnosis of myeloma:
  • Bone marrow plasmacytosis with > 10% plasma cells or sheets of plasma cells or biopsy proven plasmacytoma
  • Must have symptomatic disease that prompted the initiation of therapy (e.g., anemia, hypercalcemia, bone disease, or renal dysfunction)

• Must have completed a minimum of 1 and a maximum of 6 courses of a dexamethasone-based regimen within the past 8 weeks, including any of the following:
  • Dexamethasone alone
  • Vincristine, doxorubicin, and dexamethasone
  • Thalidomide and dexamethasone
  • Lenalidomide and dexamethasone
  • Liposomal doxorubicin and dexamethasone
  • The combination of any of the above agents and dexamethasone
  • Cyclophosphamide, lenalidomide, and dexamethasone

• Received a minimum cumulative dose of 160 mg of dexamethasone (no maximum dose specified)

• Must have not experienced progressive disease on the dexamethasone-based regimen

• Patients diagnosed with only smoldering myeloma or monoclonal gammopathy of undetermined significance are not eligible

Prior/Concurrent Therapy:

• See Disease Characteristics
• At least 14 days since prior palliative and/or localized radiotherapy
• Prior bortezomib allowed
• Concurrent bisphosphonates or growth factors (e.g., granulocyte and/or erythropoietic agents) for multiple myeloma allowed

Patient Characteristics:

• ECOG performance status 0-2
• Hemoglobin > 7 g/dL
• Platelet count > 75,000/mm³
• Absolute neutrophil count > 1,000/mm³ (without the use of growth factors to increase ANC)
• Creatinine < 2.5 mg/dL and creatinine clearance (measured or calculated) ≥ 60 mL/min
• Direct bilirubin < 1.5 mg/dL
• ALT and AST < 2.5 times upper limit of normal
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective double-method contraception for 4 weeks prior to, during, and for 4 weeks after completion of study therapy
• No active uncontrolled seizure disorder
• No seizure within the past 6 months
• No concurrent uncontrolled illness that would limit compliance with the study, including any of the following:
  • Uncontrolled hypertension
  • Symptomatic congestive heart failure
  • Unstable angina
  • Uncontrolled cardiac arrhythmia
  • Uncontrolled psychiatric illness or social situation
  • History of Steven Johnson syndrome
• No peripheral neuropathy ≥ grade 2
• No active uncontrolled infection
• Patients with a history of prior malignancy are eligible provided there is no active malignancy AND there is a low expectation of recurrence within 6 months
• Must be willing and able to receive prophylaxis with aspirin (325 mg/day) or alternative prophylaxis with low molecular weight heparin or coumadin
  • Patients with prior DVT are eligible provided they remain on the anticoagulation regimen that was prescribed for treatment of the DVT throughout study therapy

Expected Enrollment

Outcomes

Progression-free survival

Response rates (complete response and very good partial response)
Overall survival rates
Difference in rate of all grade 3 or higher toxicity
Difference in the mean change in the FACT-Ntx TOI score from study registration (prior to randomization) to 6 months post-consolidation treatment
Impact of the differential treatment survival on quality of life at clinically meaningful timepoints (i.e., prior to study randomization, at the beginning of course 5, at the end of course 8, and at 3, 6, 9, and 12 months after treatment)

Outline

Patients are stratified according to prior induction therapy with lenalidomide and dexamethasone (yes vs no) and whether or not they are in complete response after induction therapy at study registration (yes vs no). Patients are randomized to 1 of 2 treatment arms.

• Arm I: Patients receive bortezomib IV on days 1, 4, 8, and 11, oral lenalidomide once a day on days 1-14, and oral dexamethasone once a day on days 1-4. Treatment repeats every 21 days for 8 courses in the absence of disease progression or unacceptable toxicity.

• Arm II: Patients receive bortezomib IV on days 1, 4, 8, and 11 and oral dexamethasone once a day on days 1-4. Treatment repeats every 21 days for 8 courses in the absence of disease progression or unacceptable toxicity.

Quality of life is assessed periodically.

After completion of study treatment, patients are followed every 3 months for 2 years, every 6 months for 3 years, and then every 12 months for 5 years.

Fonseca R, Rajkumar SV: Consolidation therapy with bortezomib/lenalidomide/ dexamethasone versus bortezomib/dexamethasone after a dexamethasone-based induction regimen in patients with multiple myeloma: a randomized phase III trial. Clin Lymphoma Myeloma 8 (5): 315-7, 2008.[PUBMED Abstract]

Trial Contact Information

Trial Lead Organizations

Eastern Cooperative Oncology Group

Rafael Fonseca, MD, Protocol chair		Ph: 480-301-6118 Email: fonseca.rafael@mayo.edu
S. Rajkumar, MD, Protocol chair		Ph: 507-538-0591 Email: rajkumar.vincent@mayo.edu

Related Information

Featured trial article

Registry Information
Official Title		Randomized Phase III Trial of Consolidation Therapy with Bortezomib (Velcade®)- Lenalidomide (Revlimid®) -Dexamethasone (VRD) versus Bortezomib (Velcade®) - Dexamethasone (VD) for Patients With Multiple Myeloma Who Have Completed a Dexamethasone Based Induction Regimen
Trial Start Date		2007-08-21
Trial Completion Date		2009-08-25 (estimated)
Registered in ClinicalTrials.gov		NCT00522392
Date Submitted to PDQ		2007-08-07
Information Last Verified		2010-05-08
NCI Grant/Contract Number		CA21115

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