Lenalidomide and Dexamethasone With/Without Stem Cell Transplant in Patients With Multiple Myeloma

Study Overview
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Brief Summary
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The study is being done to compare the combination of lenalidomide and dexamethasone followed by autologous peripheral blood stem cell transplant (PBSCT) and lenalidomide and dexamethasone without PBSCT in patients with untreated multiple myeloma. This comparison will include how the subjects respond to each study treatment combination, and what side effects are caused by each combination.

Detailed Description
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Multiple myeloma is a malignant plasma cell proliferative disorder responsible for 11, 000 deaths each year in the United States. Approximately one third of myeloma patients develop hypercalcemia and about two thirds present with anemia. As the second most common hematologic malignancy, myeloma remains incurable. In the last forty years, options for therapy have included melphalan-prednisone, anthracyclines, and vinca alkaloids; however, relapse with those regimens continues to be inevitable with a median survival of 3 years.

Official Title
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A Randomized Clinical Trial of Lenalidomide (CC-5013) and Dexamethasone With and Without Autologous Peripheral Blood Stem Cell Transplant in Patients With Newly Diagnosed Multiple Myeloma

Conditions
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Multiple Myeloma

Intervention / Treatment
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* Procedure: Autologous peripheral blood stem cell transplant
* Drug: Lenalidomide
* Drug: Dexamethasone
* Procedure: Stem cell collection
* Drug: Melphalan
* Drug: G-CSF
* Drug: Cyclophosphamide
* Drug: Mesna


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically or cytologically confirmed Multiple Myeloma, Salmon-Durie Stage II or III or International Staging System II or III that has not been previously treated. Bone marrow plasmacytosis with > or = 10% plasma cells, or sheets of plasma cells or a biopsy-proven plasmacytoma. Measurable levels of monoclonal protein (M protein): 1 g/dL Immunoglobulin G (IgG) or .5 g/dL Immunoglobulin A (IgA) on serum protein electrophoresis or > 200 mg of monoclonal light chain on a 24 hour urine protein electrophoresis. Age > or = 18 years. Life expectancy of greater than 12 months. Eastern Cooperative Oncology Group (ECOG) performance status < or = 2 (Karnofsky > or = 60%). Adequate organ and marrow function as defined below: Hgb > or = 9 g/dL Absolute Neutrophil Count > or = 1,500/ ml Platelets > or = 50,000/mm3 Total Bilirubin < or = 1.5 mg/dL Aspartate aminotransferase (AST)(SGOT) / alanine aminotransferase (ALT)(SGPT) < or = 2.5 X upper limit of normal (ULN) Creatinine < 2.0 mg/dL Creatinine Clearance > or = 50 ml/min Registered into the mandatory Revlimid REMS® program, and be willing and able to comply with the requirements of the REMS® program. Females of reproductive potential must adhere to the scheduled pregnancy testing as required in the Revlimid REMS® program. Ability to understand and the willingness to sign a written informed consent document. Subjects with a history of prior malignancy are eligible provided there is no active malignancy and a low expectation of recurrence within 6 months. Must be willing and able to take prophylaxis with either aspirin at 81 mg/day or alternative prophylaxis with either low molecular weight heparin or warfarin as recommended. Eligible for transplant with an age up to and including 75 years. Subjects in Arm A who are refusing transplant can go onto Arm B and will be evaluated separately. Females of childbearing potential (FCBP) must have a negative serum or urine pregnancy test with a sensitivity of at least 50 milli-international units per millilitre (mIU/mL) within 10 - 14 days prior to and again within 24 hours of prescribing lenalidomide and must either commit to continued abstinence or 2 acceptable methods of birth control. FCBP must also agree to ongoing pregnancy testing. Males must agree to use a latex condom. Exclusion Criteria: Have had chemotherapy or radiotherapy for multiple myeloma within 4 weeks of baseline. Receiving any other investigational agents or therapy within 28 days of baseline. Brain metastases. Subjects who are pregnant or breast feeding. History of previous deep vein thrombosis or pulmonary embolism must be on anticoagulation therapy with low molecular weight heparin or warfarin at therapeutic dosages (e.g. International Normalized Ratio (INR) 2-3). If a subject is on full-dose anticoagulants, the following criteria should be met for enrollment: Must not have active bleeding or pathological conditions that carry high risk of bleeding (e.g. tumor involving major vessels, known varices). Must not have thrombocytopenia requiring transfusion. Must have a platelet count > 50,000. Must have stable INR between 2-3. Smoldering myeloma or monoclonal gammopathy of undetermined significance. Active, uncontrolled infection. Active, uncontrolled seizure disorder (seizures in the last 6 months). Concurrent use of other anti-cancer agents or treatments. Positive for HIV or infectious hepatitis, type B or C. Hypersensitivity to thalidomide. Any condition, including the presence of laboratory abnormalities, which places the subject at unacceptable risk.

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
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Arm A<br>Subjects will receive the current standard of care treatment. Lenalidomide and dexamethasone for four 28-day cycles followed by steam cell collection and autologous peripheral blood stem cell transplant. After 90 days, start the maintenance phase (lenalidomide days 1-21 every 28 days for two years or until your disease progresses). | Procedure: Autologous peripheral blood stem cell transplant<br>* Subjects deemed suitable by the principal investigator will undergo autologous peripheral blood stem cell transplantation on day 0.<br>Drug: Lenalidomide<br>* Administered orally at a dose 25 mg daily on days 1-21 of each 28-day cycle.<br>* Other names: Revlimid;Drug: Dexamethasone<br>* Administered orally at a dose of 40 mg daily on days 1, 8, 15, 22 of each cycle.<br>* Other names: DXM;Procedure: Stem cell collection<br>* Peripheral stem cell collection will be performed at marrow recovery, usually when white blood cell (WBC) is >2500 x 109 cells/liter; platelet count is >20 x 103/mm3.<br>* Other names: Stem Cell Mobilization;Drug: Melphalan<br>* Subjects undergoing autologous peripheral blood stem cell transplant will receive melphalan 200 mg/m2 intravenously on days -2 and -1 or only on day -2.<br>* Other names: Evomela;Drug: G-CSF<br>* Subjects will receive G-CSF subcutaneously daily beginning on day 5 and until blood counts recover.<br>* Other names: Filgrastim;Drug: Cyclophosphamide<br>* Subjects may receive up to the maximum recommended high-dose of cyclophosphamide at 4 gm/m2 intravenously.<br>* Other names: Cytophosphane;Drug: Mesna<br>* Mesna will be provided with the cyclophosphamide.<br>* Other names: Mesnex;|
| Active Comparator: Arm B<br>Subjects will receive the new treatment that will be compared with the standard of care. Lenalidomide and dexamethasone for eight 28-day cycles. After four cycles your stem cells will be collected (stem cell collection). After an additional four cycles of lenalidomide (a total of 8 cycles), start the maintenance phase (lenalidomide days 1-21 every 28 days for two years or until your disease progresses). | Drug: Lenalidomide<br>* Administered orally at a dose 25 mg daily on days 1-21 of each 28-day cycle.<br>* Other names: Revlimid;Drug: Dexamethasone<br>* Administered orally at a dose of 40 mg daily on days 1, 8, 15, 22 of each cycle.<br>* Other names: DXM;Procedure: Stem cell collection<br>* Peripheral stem cell collection will be performed at marrow recovery, usually when white blood cell (WBC) is >2500 x 109 cells/liter; platelet count is >20 x 103/mm3.<br>* Other names: Stem Cell Mobilization;Drug: Cyclophosphamide<br>* Subjects may receive up to the maximum recommended high-dose of cyclophosphamide at 4 gm/m2 intravenously.<br>* Other names: Cytophosphane;Drug: Mesna<br>* Mesna will be provided with the cyclophosphamide.<br>* Other names: Mesnex;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Complete Response Rate | The primary objective of this study is to determine the complete response rate of lenalidomide and low-dose dexamethasone versus that of lenalidomide and low-dose dexamethasone followed by autologous peripheral blood stem cell transplant in patients with newly diagnosed multiple myeloma (will include unconfirmed complete response (CR), CR and stringent complete response (sCR)). | 3 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival Rate (OS) | To compare overall survival in subjects receiving autologous peripheral blood stem cell transplant after undergoing induction therapy with lenalidomide and dexamethasone versus in those receiving only lenalidomide and dexamethasone, followed by lenalidomide maintenance in both arms. Only patients who achieved at least a partial response (PR) following 4 cycles of induction were included in the analysis. | 4 years | 
| Overall Survival Rate (OS) | To compare overall survival in subjects receiving autologous peripheral blood stem cell transplant after undergoing induction therapy with lenalidomide and dexamethasone versus in those receiving only lenalidomide and dexamethasone, followed by lenalidomide maintenance in both arms. Only patients who achieved at least a partial response (PR) following 4 cycles of induction were included in the analysis. | 2 years | 
| Progression Free Survival (PFS) | PFS is the length of time during and after the treatment of a disease, such as cancer, that a patient lives with the disease but it does not get worse. | 4 years | 
| Progression Free Survival (PFS) | PFS is the length of time during and after the treatment of a disease, such as cancer, that a patient lives with the disease but it does not get worse. | 2 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Stem cell transplant, plasma cell myeloma, multiple myeloma