Clinical Trials (PDQ®)
|Phase III||Treatment||Closed||18 and over||NCI||NCI-2009-00521|
CDR0000561758, ECOG-E1A05, E1A05, U10CA021115, U10CA180820, NCT00522392
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.
Further Study Information
I. To compare the progression-free survival (PFS) for two consolidation regimens: bortezomib, lenalidomide, and dexamethasone (VRD) versus bortezomib and dexamethasone (VD) only.
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.
- 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:
- 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
Trial Lead Organizations/Sponsors
National Cancer Institute
|Rafael Fonseca||Principal Investigator|
Link to the current ClinicalTrials.gov record.
NLM Identifer NCT00522392
ClinicalTrials.gov processed this data on September 16, 2014
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