Lenalidomide and Dexamethasone With/Without Stem Cell Transplant in Patients With Multiple Myeloma
Condition: Multiple Myeloma
MeSH terms: Multiple Myeloma; Neoplasms, Plasma Cell
Intervention: Autologous peripheral blood stem cell transplant; Lenalidomide; Dexamethasone; Stem cell collection; Melphalan; G-CSF; Cyclophosphamide; Mesna
Intervention description: Subjects deemed suitable by the principal investigator will undergo autologous peripheral blood stem cell transplantation on day 0.; Administered orally at a dose 25 mg daily on days 1-21 of each 28-day cycle.; Administered orally at a dose of 40 mg daily on days 1, 8, 15, 22 of each cycle.; 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.; 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.; Subjects will receive G-CSF subcutaneously daily beginning on day 5 and until blood counts recover.; Subjects may receive up to the maximum recommended high-dose of cyclophosphamide at 4 gm/m2 intravenously.; Mesna will be provided with the cyclophosphamide.
Intervention MeSH terms: Dexamethasone; Cyclophosphamide; Melphalan; Lenalidomide; Lenograstim
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 60.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Stem cell transplant; plasma cell myeloma; multiple myeloma

Summary:

      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.
    

Eligibility criteria:

        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.