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

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

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.

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.

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.