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Phase III Randomized Study of Lenalidomide With Standard-Dose Versus Low-Dose Dexamethasone With or Without Salvage Therapy Comprising Thalidomide and Dexamethasone in Patients With Newly Diagnosed Multiple Myeloma
Alternate Title Basic Trial Information Objectives Entry Criteria Expected Enrollment Outcomes Outline Published Results Related Publications Trial Contact Information Registry Information
Alternate Title
Lenalidomide and Dexamethasone With or Without Thalidomide in Treating Patients With Multiple Myeloma
Basic Trial Information
Phase | Type | Status | Age | Protocol IDs |
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Phase III | Treatment | Closed | 18 and over | ECOG-E4A03 E4A03, NCT00098475 |
Special Category:
CTSU trial Objectives Primary - Compare the response rate in patients with newly diagnosed multiple myeloma treated with lenalidomide and standard-dose vs low-dose dexamethasone.
- Compare the toxicity of these regimens in these patients.
Secondary - Determine the response rate in patients who do not achieve an objective response at any point during the first 4 courses of lenalidomide and dexamethasone and are subsequently treated with salvage therapy comprising thalidomide and dexamethasone.
- Determine the efficacy of aspirin
(325 mg/day) versus warfarin (dose adjusted to maintain a target INR of 2-3) in
preventing deep vain thrombosis in patients treated with these regimens.
Entry Criteria Disease Characteristics:
- Diagnosis of multiple myeloma within the past 90 days, confirmed by the following criteria:
- Bone marrow plasmacytosis with ≥ 10% plasma cells or sheets of plasma cells OR biopsy-proven plasmacytoma within the past 4 weeks
- Measurable monoclonal protein ≥ 1.0 g/dL by serum protein electrophoresis OR monoclonal light chain ≥ 200 mg by 24-hour urine protein electrophoresis within the past 4 weeks
- Symptomatic disease
- Prior plasmacytoma treated with curative-intent radiotherapy allowed provided disease progressed to active multiple myeloma
- No smoldering myeloma
- No monoclonal gammopathy of undetermined significance
Prior/Concurrent Therapy:
Biologic therapy - No concurrent sargramostim (GM-CSF)
Chemotherapy Endocrine therapy - No prior glucocorticosteroid therapy for multiple myeloma
- The following treatments for non-malignant disorders are allowed:
- Prior systemic glucocorticosteroids
- Prior or concurrent topical or localized glucocorticosteroids
- Concurrent systemic glucocorticosteroids at a dose of ≤ 10 mg of prednisone per day (or equivalent)
Radiotherapy - See Disease Characteristics
- At least 4 weeks since prior palliative and/or localized radiotherapy
Surgery Other - No prior systemic therapy for multiple myeloma except bisphosphonates
Patient Characteristics:
Age Performance status Life expectancy Hematopoietic - Hemoglobin > 7 g/dL
- Platelet count > 75,000/mm3
- Absolute neutrophil count > 1,000/mm3
Hepatic - Bilirubin ≤ 1.5 mg/dL
- ALT and AST ≤ 2.5 times upper limit of normal (ULN)
Renal Cardiovascular - No uncontrolled hypertension
- No uncontrolled cardiac arrhythmia
- No symptomatic congestive heart failure
- No unstable angina
- No prior or concurrent deep vein thrombosis
Pulmonary - No prior or concurrent pulmonary embolism
Other - Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective double-method contraception (1 highly effective and one additional method) for 4 weeks prior, during, and for 4 weeks after completion of study treatment
- No other active malignancy
- Prior malignancy with a low expectation of recurrence within the next 6 months allowed
- No prior Stevens Johnson syndrome
- No active uncontrolled seizure disorder
- No seizures within the past 6 months
- No active uncontrolled infection
- No uncontrolled psychiatric illness or social situation that would preclude study compliance
- No peripheral neuropathy ≥ grade 2 due to other medical conditions
- No other uncontrolled illness
- Patients must be willing and able to take antithrombosis prophylaxis
- Patients must
Expected Enrollment 412A total of 412 patients (206 per treatment arm) will be accrued for this study within 24 months. Outcomes Primary Outcome(s)Comparison of treatment regimens
Secondary Outcome(s)Toxicity Response rate
Outline This is a randomized, multicenter study. Patients are randomized to 1 of 2 treatment arms. - Arm I: Patients receive oral lenalidomide once daily on days 1-21, oral acetylsalicyclic acid (or other deep vein thrombosis prophylaxis at the discretion of the principal investigator) once daily on days 1-28, and standard-dose oral dexamethasone once daily on days 1-4, 9-12, and 17-20.
- Arm II: Patients receive oral lenalidomide and acetylsalicyclic acid as in arm I and low-dose oral dexamethasone once daily on days 1, 8, 15, and 22.
In both arms, courses repeat every 28 days in the absence of unacceptable toxicity or disease progression. Patients not responding at any point during the first 4 courses of lenalidomide and dexamethasone are assigned to 1 of 2 salvage therapy arms. Patients who progress during treatment on arms I or II have the option to register on salvage therapy arms III or IV respectively. - Arm III (patients with no response after treatment on arm I): Patients receive oral thalidomide once daily on days 1-28 and standard-dose oral dexamethasone once daily on days 1-4, 9-12, and 17-20.
- Arm IV (patients with no response after treatment on arm II): Patients receive oral thalidomide as in arm III and low-dose oral dexamethasone once daily on days 1, 8, 15, and 22.
In both salvage therapy arms, courses repeat every 28 days in the absence of unacceptable toxicity or disease progression. After completion of 4 courses of therapy, patients may undergo stem cell harvest (using growth factors only) for cryopreservation. Patients are followed every 3 months for 2 years, every 6 months for 3 years, and then annually for 2 years. Published ResultsJacobus S, Kumar S, Callander NS, et al.: Effect of venous thrombotic events on overall survival in multiple myeloma: analysis of thrombotic events occurring in E4A03: A randomized trial of lenalidomide plus high-dose dexamethasone (RD) versus lenalidomide plus low-dose dexamethasone (Rd) in newly diagnosed multiple myeloma, a trial coordinated by the Eastern Cooperative Oncology Group (ECOG). [Abstract] Blood 112 (11): A-1740, 2008. Rajkumar SV, Jacobus S, Callander N, et al.: A randomized phase III trial of lenalidomide plus high-dose dexamethasone versus lenalidomide plus low-dose dexamethasone in newly diagnosed multiple myeloma (E4A03): a trial coordinated by the Eastern Cooperative Oncology Group. [Abstract] Blood 108 (11): A-799, 2006. Related PublicationsBallester O: The emperor's new clothes or the current practice of clinical trials for multiple myeloma in the USA. Cancer Invest 26 (5): 445-7, 2008.[PUBMED Abstract]
Trial Contact Information
Trial Lead Organizations Eastern Cooperative Oncology Group | | | S. Rajkumar, MD, Protocol chair | | | | Rafael Fonseca, MD, Protocol co-chair | | | |
Registry Information | | Official Title | | A Randomized Phase III Study of CC-5013 plus Dexamethasone versus CC-5013 plus Low Dose Dexamethasone in Multiple Myeloma With Thalidomide plus Dexamethasone Salvage Therapy for Non-Responders | | Trial Start Date | | 2004-10-26 | | Registered in ClinicalTrials.gov | | NCT00098475 | | Date Submitted to PDQ | | 2004-10-26 | | Information Last Verified | | 2007-04-12 | | NCI Grant/Contract Number | | CA21115 |
Note: The purpose of most clinical trials listed in this database is to test new cancer treatments, or new methods of diagnosing, screening, or preventing cancer. Because all potentially harmful side effects are not known before a trial is conducted, dose and schedule modifications may be required for participants if they develop side effects from the treatment or test. The therapy or test described in this clinical trial is intended for use by clinical oncologists in carefully structured settings, and may not prove to be more effective than standard treatment. A responsible investigator associated with this clinical trial should be consulted before using this protocol. Back to Top |
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