Bortezomib and Dexamethasone With or Without Lenalidomide in Treating Patients With Multiple Myeloma Previously Treated With Dexamethasone - Full Text View

Sponsor:	Eastern Cooperative Oncology Group
Collaborator:	National Cancer Institute (NCI)
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00522392

Purpose

RATIONALE: Bortezomib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as dexamethasone, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Lenalidomide may stimulate the immune system in different ways and stop cancer cells from growing. It is not yet known whether giving bortezomib together with dexamethasone is more effective with or without lenalidomide in treating multiple myeloma.

PURPOSE: This randomized phase III trial is studying bortezomib, dexamethasone, and lenalidomide to see how well they work compared with bortezomib and dexamethasone in treating patients with multiple myeloma previously treated with dexamethasone.

Condition	Intervention	Phase
Multiple Myeloma and Plasma Cell Neoplasm	Drug: bortezomib Drug: dexamethasone Drug: lenalidomide	Phase III

Study Type:	Interventional
Study Design:	Treatment, Randomized, Open Label
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

Resource links provided by NLM:

Genetics Home Reference related topics: aceruloplasminemia hemophilia

MedlinePlus related topics: Cancer Multiple Myeloma

Drug Information available for: Dexamethasone Dexamethasone acetate Doxiproct plus Bortezomib Lenalidomide CC 5013 Dexamethasone Sodium Phosphate

U.S. FDA Resources

Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:

Progression-free survival [ Designated as safety issue: No ]

Secondary Outcome Measures:

Response rates (complete response and very good partial response) [ Designated as safety issue: No ]
Overall survival rates [ Designated as safety issue: No ]
Difference in rate of all grade 3 or higher toxicity [ Designated as safety issue: Yes ]
Difference in the mean change in the FACT-Ntx TOI score from study registration (prior to randomization) to 6 months post-consolidation treatment [ Designated as safety issue: No ]
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) [ Designated as safety issue: No ]

Estimated Enrollment:	392
Study Start Date:	August 2007
Estimated Primary Completion Date:	August 2009 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Arm I: Experimental 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.	Drug: bortezomib Given IV Drug: dexamethasone Given orally Drug: lenalidomide Given orally
Arm II: Active Comparator 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.	Drug: bortezomib Given IV Drug: dexamethasone Given orally

Detailed Description:

OBJECTIVES:

Primary

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

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

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.

Eligibility

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

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

PATIENT CHARACTERISTICS:

ECOG performance status 0-2
Hemoglobin > 7 g/dL
Platelet count > 75,000/mm^3
Absolute neutrophil count > 1,000/mm^3 (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

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00522392

Show 245 Study Locations

Sponsors and Collaborators

Eastern Cooperative Oncology Group

National Cancer Institute (NCI)

Investigators

Study Chair:	Rafael Fonseca, MD	Mayo Clinic
Study Chair:	S. V. Rajkumar, MD	Mayo Clinic

More Information

Additional Information:

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

Featured trial article This link exits the ClinicalTrials.gov site

Publications:

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. 2008 Oct;8(5):315-7.

Responsible Party:	ECOG Group Chair's Office ( Robert L. Comis )
Study ID Numbers:	CDR0000561758, ECOG-E1A05
Study First Received:	August 28, 2007
Last Updated:	February 5, 2010
ClinicalTrials.gov Identifier:	NCT00522392 History of Changes
Health Authority:	Unspecified

Keywords provided by National Cancer Institute (NCI):

stage II multiple myeloma
stage III multiple myeloma
stage I multiple myeloma

Additional relevant MeSH terms:

Anti-Inflammatory Agents
Dexamethasone
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Blood Protein Disorders
Physiological Effects of Drugs
Hormones, Hormone Substitutes, and Hormone Antagonists
Antiemetics
Paraproteinemias
Hemostatic Disorders
Hormones
Hemorrhagic Disorders
Therapeutic Uses
Cardiovascular Diseases
Dexamethasone acetate

Immunoproliferative Disorders
Neoplasms by Histologic Type
Antineoplastic Agents, Hormonal
Immune System Diseases
Hematologic Diseases
Bortezomib
Gastrointestinal Agents
Vascular Diseases
Lenalidomide
Enzyme Inhibitors
Glucocorticoids
Pharmacologic Actions
Protease Inhibitors
Multiple Myeloma
Neoplasms

ClinicalTrials.gov processed this record on February 08, 2010