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

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00522392
First received: August 28, 2007
Last updated: June 17, 2014
Last verified: December 2013
  Purpose

This randomized phase III trial compares bortezomib, dexamethasone, and lenalidomide with bortezomib and dexamethasone to see how well they work in treating patients with multiple myeloma previously treated with dexamethasone. 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 and dexamethasone is more effective with or without lenalidomide in treating multiple myeloma.


Condition Intervention Phase
Stage I Multiple Myeloma
Stage II Multiple Myeloma
Stage III Multiple Myeloma
Drug: bortezomib
Drug: lenalidomide
Drug: dexamethasone
Other: quality-of-life assessment
Other: laboratory biomarker analysis
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
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:


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

Primary Outcome Measures:
  • PFS of two consolidation regimens [ Time Frame: Time from consolidation randomization until progression or death of any cause, assessed up to 10 years ] [ Designated as safety issue: No ]
    PFS in each of the arms will be estimated using the method of Kaplan and Meier. PFS between the two arms will be compared using one-sided stratified log-rank test.


Secondary Outcome Measures:
  • Response rates (complete response [CR] and VGPR) [ Time Frame: Up to 10 years ] [ Designated as safety issue: No ]
    Compared between the VD and VRD arms using the Fisher's exact test. Patients that start consolidation in CR after their dexamethasone-based induction are not included in these analyses.

  • Overall survival (OS) rates of the two consolidation regimens [ Time Frame: Up to 10 years ] [ Designated as safety issue: No ]
    OS in each of the arms will be estimated using the method of Kaplan and Meier. OS between the two arms will be compared using two-sided stratified log-rank test.

  • Rate of all grade 3 or higher toxicities, graded using the National Cancer Institute CTCAE version 4.0 [ Time Frame: Up to 30 days ] [ Designated as safety issue: Yes ]
    Compared between the two regimens using the Fisher's Exact Test.

  • Change in QOL as assessed by the FACT Ntx TOI and the Multiple Myeloma Subscale (MMS) instruments [ Time Frame: Baseline to 6 months post consolidation treatment ] [ Designated as safety issue: No ]
    A two-sided t-test with a 0.05 significance level will be used.

  • Impact of the differential treatment survival (PFS) on QOL at clinically meaningful time-points [ Time Frame: Up to 18 months post-registration ] [ Designated as safety issue: No ]
    The difference in the FACT-Ntx TOI mean change scores between patients that experience disease progression (PD) and patients who do not experience PD using mixed effects model will be collected.


Other Outcome Measures:
  • MMS scores [ Time Frame: 6 months post consolidation treatment ] [ Designated as safety issue: No ]
    Differences in the MMS between the two arms and the correlation among various elements of the FACT-Ntx TOI and the new MMS will be assessed.

  • Clinical measures, including EGOG performance status, bone disease, International Staging System stage, and renal function [ Time Frame: Up to 10 years ] [ Designated as safety issue: No ]
    The relationships between individual elements of the FACT-Ntx TOI as well as the MMS instrument and important clinical measures in an effort to discern criterion validity. These relationships will be analyzed with 1-way multivariate analysis of variance (MANOVA). When MANOVA is significant then a univariate analysis of variance is done on each dependent variable.


Enrollment: 47
Study Start Date: September 2007
Primary Completion Date: April 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm I (VRD)
Patients receive bortezomib IV on days 1, 4, 8, and 11, lenalidomide PO QD on days 1-14, and dexamethasone PO QD on days 1, 8, and 15. Treatment repeats every 21 days for 8 courses in the absence of disease progression or unacceptable toxicity.
Drug: bortezomib
Given IV
Other Names:
  • LDP 341
  • MLN341
  • VELCADE
Drug: lenalidomide
Given PO
Other Names:
  • CC-5013
  • IMiD-1
  • Revlimid
Drug: dexamethasone
Given PO
Other Names:
  • Aeroseb-Dex
  • Decaderm
  • Decadron
  • DM
  • DXM
Other: quality-of-life assessment
Ancillary studies
Other Name: quality of life assessment
Other: laboratory biomarker analysis
Correlative studies
Active Comparator: Arm II (VD)
Patients receive bortezomib IV on days 1, 4, 8, and 11 and dexamethasone PO QD on days 1, 8, and 15. Treatment repeats every 21 days for 8 courses in the absence of disease progression or unacceptable toxicity.
Drug: bortezomib
Given IV
Other Names:
  • LDP 341
  • MLN341
  • VELCADE
Drug: dexamethasone
Given PO
Other Names:
  • Aeroseb-Dex
  • Decaderm
  • Decadron
  • DM
  • DXM
Other: quality-of-life assessment
Ancillary studies
Other Name: quality of life assessment
Other: laboratory biomarker analysis
Correlative studies

Detailed Description:

PRIMARY OBJECTIVES:

I. To compare the progression-free survival (PFS) for two consolidation regimens: bortezomib, lenalidomide, and dexamethasone (VRD) versus bortezomib and dexamethasone (VD) only.

SECONDARY OBJECTIVES:

I. To determine the incremental ability of VRD versus VD in attaining a complete response or a very good partial response (VGPR) in patients receiving induction therapy with a dexamethasone based induction regimen.

II. To compare the overall survival, measured from the time of study entry. III. Evaluate response rate and PFS according to cytogenetic category (by gene expression and fluorescence in situ hybridization [FISH]).

IV. To evaluate the toxicity of the two regimens. V. To compare quality of life (QOL) based on the Functional Assessment of Cancer Therapy (FACT)-Neurotoxicity (Ntx) Trial Outcome Index (TOI) of patients receiving VD to those receiving VRD from registration to 6 months post consolidation treatment.

VI. To examine the impact of differential treatment response (PFS), if observed, on QOL based on the FACT-Ntx TOI up to 12 months post consolidation treatment.

VII. To obtain prospective data on multiple myeloma specific QOL attributes.

OUTLINE: Patients are randomized to 1 of 2 treatment arms.

ARM I: Patients receive bortezomib intravenously (IV) on days 1, 4, 8, and 11, lenalidomide orally (PO) once daily (QD) on days 1-14, and dexamethasone PO QD on days 1, 8, and 15. 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 dexamethasone PO QD on days 1, 8, and 15. Treatment repeats every 21 days for 8 courses in the absence of disease progression or unacceptable toxicity.

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

Inclusion Criteria:

  • Patients must be diagnosed with symptomatic multiple myeloma, that was symptomatic at time of initial diagnosis, but may be asymptomatic at the time of registration based on induction therapy
  • For the original diagnosis of myeloma patients should have met the following criteria at one point in their disease course:

    • Bone marrow plasmacytosis with >= 10% plasma cells or sheets of plasma cells or biopsy proven plasmacytoma
    • Patient must have had symptomatic disease at initial diagnosis that prompted the initiation of therapy, as well as evidence of end-organ damage due to the multiple myeloma, at the time of diagnosis of at least one of the following:

      • Anemia
      • Hypercalcemia
      • Bone disease (lytic bone lesions or pathologic fracture)
      • Renal dysfunction NOTE: Patients with smoldering myeloma (serum m protein >= 3 gm/dL or bone marrow plasma cells >= 10% or greater plus no evidence of anemia, hypercalcemia, lytic bone lesions or renal dysfunction) and monoclonal gammopathy of undetermined significance (serum m protein < 3 gm/dL and bone marrow plasma cells < 10% or greater plus no evidence of anemia, hypercalcemia, lytic bone lesions or renal dysfunction) are not eligible
  • Patients may have prior exposure to bortezomib
  • The following induction regimens will be considered adequate for enrollment in this trial:

    • 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
  • Patients must have received a minimum of 1 cycle, maximum of 6 cycles, of a dexamethasone-based regimen; patient must not have experienced progressive disease on such therapy
  • Patients must have received the minimum cumulative dose of dexamethasone of 160 mg (sum of induction treatment) with no maximum dose specified
  • Patients must be no more than 8 weeks from the last day of last cycle of induction treatment
  • Patients must have been offered and refused front-line stem cell transplant OR patients must not be eligible for front-line stem cell transplant.
  • Bone marrow aspiration and/or biopsy must be obtained =< 28 days prior to randomization
  • All tests below must be performed =< 28 days prior to randomization:

    • Kappa free light chain mg/dL
    • Lambda free light chain mg/dL
    • Serum M-protein by serum protein electrophoresis (SPEP)
    • Urine M-protein light chain excretion by urine protein electrophoresis (UPEP) NOTE: UPEP (on a 24 hour collection) is required, no substitute method is acceptable; urine must be followed monthly if at baseline (at the initiation of induction therapy) the patient had a urinary M-spike that was >= 200 mg/24 hr; please note that if both serum and urine m-components are present, both must be followed in order to evaluate response
  • Hemoglobin > 7 g/dL
  • Platelet count > 75,000 cells/mm^3
  • Absolute neutrophil count > 1000 cells/mm^3 (should be without use of growth factors to increase absolute neutrophil count [ANC])
  • Creatinine < 2.5 mg/dL and creatinine clearance (measured or calculated) >= 60 mL/min
  • Direct bilirubin =< 1.5 mg/dL
  • Serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) and serum glutamic oxaloacetic transaminase (SGOT) (aspartate aminotransferase [AST]) =< 2.5 times the upper limit of normal
  • Patients may be receiving bisphosphonates or erythropoietin growth factors (erythropoietic agents) for multiple myeloma
  • Prior palliative and/or localized radiation therapy is permitted, provided at least 14 days have passed from date of last radiation therapy to date of randomization
  • Patients must not have active, uncontrolled seizure disorder; patients must have had no seizures in the last 6 months
  • Patients must be willing and able to take prophylaxis with either aspirin at 325 mg/day or alternative prophylaxis with either low molecular weight heparin or Coumadin; (patients with prior deep vein thrombosis [DVT] are eligible provided they remain on the anticoagulation regimen that was prescribed for treatment of the DVT throughout the protocol therapy)
  • Patients must not have uncontrolled inter-current illness that would limit compliance with the study including:

    • Uncontrolled hypertension
    • Symptomatic congestive heart failure
    • Unstable angina
    • Uncontrolled cardiac arrhythmia
    • Uncontrolled psychiatric illness or social situation
    • Prior history of Stevens Johnson syndrome
  • Patients must be competent to understand the study as explained in the consent form
  • Eastern Cooperative Oncology Group (ECOG) performance status 0, 1, or 2
  • Patients must not have grade 2 or higher peripheral neuropathy by Common Terminology Criteria for Adverse Events (CTCAE) version 3.0
  • Patients must not have an active, uncontrolled infection
  • Female patients MUST NOT be pregnant or breastfeeding; for women of childbearing potential, a negative serum pregnancy test with a sensitivity of at least 25 mIU/mL is required within 14 days prior to randomization and female patients on Arm A must be retested within 24 hours prior to initiation of treatment, weekly for the first 4 weeks of treatment and then every 4 weeks if the patient's periods are regular or every 2 weeks if they are not; further, they must either commit to continued abstinence from heterosexual intercourse or begin TWO acceptable methods of birth control: one highly effective method and one additional effective method AT THE SAME TIME, at least 28 days before starting lenalidomide; females of childbearing potential (FCBP) must also agree to ongoing pregnancy testing; men must agree to use a latex condom during sexual contact with a FCBP, even if they have had a successful vasectomy; a FCBP is a sexually mature woman who: 1) has not undergone a hysterectomy or bilateral oophorectomy; or 2) has not been naturally postmenopausal for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months); all patients must be counseled by a trained counselor every 28 days about pregnancy precautions and risks of fetal exposure
  • Sexually active males must be willing to use a condom (even if they have undergone a prior vasectomy) while having intercourse with any woman, while taking lenalidomide, and for 4 weeks after stopping treatment
  • Patients with a history of prior malignancy are eligible provided there is no active malignancy and a low expectation of recurrence within 6 months
  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: NCT00522392

  Show 276 Study Locations
Sponsors and Collaborators
Investigators
Principal Investigator: Rafael Fonseca ECOG-ACRIN Cancer Research Group
  More Information

No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00522392     History of Changes
Other Study ID Numbers: NCI-2009-00521, NCI-2009-00521, CDR0000561758, ECOG-E1A05, E1A05, E1A05, U10CA021115, U10CA180820
Study First Received: August 28, 2007
Last Updated: June 17, 2014
Health Authority: United States: Food and Drug Administration

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
Dexamethasone 21-phosphate
Bortezomib
Lenalidomide
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
Gastrointestinal Agents

ClinicalTrials.gov processed this record on September 14, 2014