Lenalidomide, Cyclophosphamide, and Dexamethasone in Treating Patients With Newly Diagnosed Multiple Myeloma

Study Overview
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Brief Summary
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RATIONALE: Lenalidomide may stop the growth of multiple myeloma by blocking blood flow to the cancer. Drugs used in chemotherapy, such as cyclophosphamide and dexamethasone, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving lenalidomide together with cyclophosphamide and dexamethasone may kill more cancer cells.> PURPOSE: This phase II trial is studying how well giving lenalidomide together with cyclophosphamide and dexamethasone works in treating patients with newly diagnosed multiple myeloma.

Detailed Description
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OBJECTIVES: Primary * Assess the response rate in patients with newly diagnosed active multiple myeloma treated with lenalidomide, cyclophosphamide, and dexamethasone. Secondary Assess the toxicity of this regimen in these patients. Determine the time to progression in patients treated with this regimen. OUTLINE: Patients receive oral lenalidomide on days 1-21, oral cyclophosphamide on days 1, 8, and 15, and oral dexamethasone on days 1, 8, 15, and 22. Treatment repeats every 28 days for 4-12 courses in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed every 6 months for up to 5 years.

Official Title
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A Phase II Trial of Revlimid, Cyclophosphamide, and Dexamethasone in Patients With > Newly Diagnosed Active Multiple Myeloma

Conditions
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Multiple Myeloma and Plasma Cell Neoplasm

Intervention / Treatment
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* Drug: cyclophosphamide
* Drug: dexamethasone
* Drug: lenalidomide


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Diagnosis of multiple myeloma Newly diagnosed disease Symptomatic disease Measurable or evaluable disease, defined by ≥ 1 of the following criteria: Serum monoclonal protein ≥ 1.0 g by protein electrophoresis Monoclonal protein > 200 mg by 24-hour urine electrophoresis Serum immunoglobulin free light chain ≥ 10 mg/dL AND abnormal serum immunoglobulin kappa to lambda free light chain ratio Monoclonal bone marrow plasmacytosis ≥ 30% (evaluable disease) Measurable soft tissue plasmacytoma not previously irradiated No monoclonal gammopathy of undetermined significance or smoldering myeloma PATIENT CHARACTERISTICS: ECOG performance status (PS) 0-2 (ECOG PS 3 allowed if secondary to pain) ANC ≥ 1,500/mm^3 Platelet count ≥ 75,000/mm^3 Hemoglobin ≥ 8.0 g/dL Creatinine ≤ 2.5 mg/dL Not pregnant or nursing Negative pregnancy test Fertile patients must use effective double-method contraception (1 highly effective and 1 additional method) for 1 month before, during, and for 4 weeks after completion of study therapy No uncontrolled infection No other active malignancy No other malignancies within the past 5 years except for currently treated basal cell or squamous cell carcinoma of the skin or carcinoma in situ of the cervix or breast No NYHA class III-IV congestive heart failure No untreated active deep vein thrombosis PRIOR CONCURRENT THERAPY: At least 3 weeks since prior radiotherapy for solitary plasmacytoma Prior clarithromycin, therapeutic dehydroepiandrosterone (DHEA), anakinra, pamidronate disodium, or zoledronic acid allowed No prior cytotoxic chemotherapy No prior corticosteroids (except for treatment of a nonmalignant disorder) Concurrent corticosteroids (prednisone ≤ 20 mg/per day) allowed No concurrent radiotherapy except palliative radiotherapy for a single painful bone lesion or fracture

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Lenalidomide/Cyclophosphamide/Dexamethasone<br> | Drug: cyclophosphamide<br>* 300 mg/m2 administrated by PO (with food)on Days 1, 8, 15 (up to 12 cycles) OR 300 mg administrated by PO (with food)on Days 1, 8, 15 (up to 12 cycles)<br>* Other names: Cytoxan, CTX, Neosar®;Drug: dexamethasone<br>* 40 mg administrated by PO (with food)on Days 1, 8, 15 & 22<br>* Other names: Decadron;Drug: lenalidomide<br>* 25 mg administrated by PO (with food)on Days 1-21<br>* Other names: Revlimid®;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants Who Achieved a Confirmed Response (CR), Very Good Partial Response (VGPR) or Partial Response (PR) During Treatment | Response that was confirmed on 2 consecutive evaluations during treatment Complete Response(CR): Complete disappearance of M-protein from serum & urine on immunofixation, normalization of Free Light Chain (FLC) ratio & <5% plasma cells in bone marrow (BM) Very Good Partial Response(VGPR): >=90% reduction in serum M-component; Urine M-Component <100 mg per 24 hours; <=5% plasma cells in BM Partial Response PR): >= 50% reduction in serum M-Component and/or Urine M-Component >= 90% reduction or <200 mg per 24 hours; or >= 50% decrease in difference between involved and uninvolved FLC levels | Duration of Treatment (up to 5 years) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival (OS) | OS was defined as the time from registration to death of any cause. Participants were followed for a maximum of 5 years from randomization. The median OS with 95%CI was estimated using the Kaplan Meier method. | up to 5 years | 
| Progression-free Survival (PFS) | PFS was defined as the time from registration to progression or death due to any cause. The median PFS with 95%CI was estimated using the Kaplan Meier method.> Progression was defined as any one or more of the following:> An increase of 25% from lowest confirmed response in:> Serum M-component (absolute increase >= 0.5g/dl)> Urine M-component (absolute increase >= 200mg/24hour> Difference between involved and uninvolved Free Light Chain levels (absolute increase >= 10mg/dl> Bone marrow plasma cell percentage (absolute increase of >=10%) | up to 5 years | 
| Duration of Response (DOR) | Duration of response was calculated from the documentation (date) of first response (CR, VGPR, or PR) until the date of progression or last follow-up in the subset of patients who responded. The median DOR with 95%CI was estimated using the Kaplan Meier method. | up to 5 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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stage I multiple myeloma, stage II multiple myeloma, stage III multiple myeloma