Lenalidomide (Revlimid®) Plus Low-dose Dexamethasone (Ld x 4 Cycles) Then Stem Cell Collection Followed by Randomization to Continued Ld or Stem Cell Transplantation (SCT) Plus Maintenance L
Condition: Multiple Myeloma
MeSH terms: Multiple Myeloma; Neoplasms, Plasma Cell
Intervention: Stem cell transplant x 1 or x 2; lenalidomide and dexamethasone
Intervention description: After 4 cycles of Ld, eligible patients will undergo stem cell mobilization and collection with standard-of-care cyclophosphamide and Neupogen (G-CSF) or with plerixafor G-CSF. Mobilization with cyclophosphamide is preferred, but plerixafor is also allowed. Ld will be held for at least 2 weeks prior to stem cell mobilization.
On the SCT arm, patients not achieving VGPR by 3 months after the 1st SCT will undergo a 2nd SCT. All patients, after one or two SCT, will receive maintenance L.; Patients will then be randomized to continued Ld or high-dose melphalan with SCT. On the SCT arm patients not achieving VGPR by 3 months after the 1st SCT will undergo a 2nd SCT. All patients after one or two SCT, will receive maintenance L.
Intervention MeSH terms: Dexamethasone; Dexamethasone acetate; Lenalidomide; Melphalan; BB 1101
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 67.0
Sex: All
Minimum age: 18 Years
Maximum age: 75 Years
Healthy volunteers: No
Keywords: CYCLOPHOSPHAMIDE (CYTOXAN); DEXAMETHASONE; G-CSF; Lenalidomide; MELPHALAN; PEG-FILGRASTIM (NEULASTA); 08-121

Summary:

      The purpose of this study is to compare the effects, good and bad, of two ways to treat
      patients with standard-risk symptomatic multiple myeloma. Patients with standard-risk myeloma
      have myeloma with specific features: levels of 2 blood tests have to be in a specific range
      and there can be no myeloma tumors found outside of the bones or bone marrow, the areas where
      myeloma is usually discovered. In past clinical studies, patients with standard-risk myeloma
      have done well with intensive therapy in the form of stem cell transplant. But multiple
      myeloma is not curable and, although it may respond to standard treatments including stem
      cell transplant, myeloma always recurs.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Age ≥ 18 and ≤ 75

          -  Histologic and serologic findings from MSKCC confirming the diagnosis of multiple
             myeloma. Standard diagnostic criteria for multiple myeloma will be used, as per the
             revised International Myeloma Working Group diagnostic criteria.

          -  Patients must have symptomatic multiple myeloma without advanced organ damage (such as
             multiple fractures or advanced bone disease causing immobilization, renal failure,
             spinal cord compression, or organ compromise due to soft tissue plasmacytoma). If
             immediate therapy with radiation and high-dose steroids (eg, for cord compression) or
             with bortezomib-based therapy (eg, for renal failure) is required, the patient is not
             eligible for this trial.

          -  Patients may have received 1 cycle of prior therapy with dexamethasone for multiple
             myeloma.

          -  Adequate organ function is required, defined as follows:

          -  ANC ≥ 1,500/μl and platelets ≥ 100,000/μl (unless low ANC and platelets are due to
             multiple myeloma)

          -  Serum bilirubin ≤ 2.0 mg/dl

          -  AST, ALT and alkaline phosphatase < 3 times the upper limit of laboratory normal

          -  Adequate renal function as assessed by calculated creatinine using Cockcroft-Gault
             estimation of CrCl (see Appendix I): Subjects must have calculated creatinine
             clearance ≥ 30ml/min by Cockcroft-Gault formula

          -  Performance status (ECOG) ≤ 2 (Appendix E).

          -  Eligible for SCT with LVEF ≥ 50% by MUGA or ECHO, and diffusing capacity > 50%
             predicted by pulmonary function testing

          -  Ability to understand the investigational nature of this study and to give informed
             consent

          -  All study participants must be registered into the mandatory Revlimid REMS® program,
             and be willing and able to comply with the requirements the of Revlimid REMS® program

          -  Females of childbearing potential (FCBP)† must have a negative serum or urine
             pregnancy test with a sensitivity of at least 50 mIU/mL within 10 - 14 days prior to
             and again within 24 hours prior to prescribing lenalidomide for cycle 1 (prescriptions
             must be filled within 7 days) and must either commit to continued abstinence from
             heterosexual intercourse or begin TWO acceptable methods of birth control, one highly
             effective method and one additional effective method AT THE SAME TIME, at least 28
             days before she starts taking lenalidomide. FCBP must also agree to ongoing pregnancy
             testing. Men must agree not to father a child and agree to use a latex condom during
             sexual contact with females of child bearing potential even if they have had a
             successful vasectomy. See Appendix C: Risks of Fetal Exposure, Pregnancy Testing
             Guidelines and Acceptable Birth Control Methods.

          -  Able to take aspirin 325mg or 81mg daily as prophylactic anticoagulation (patients
             intolerant to ASA may use Coumadin or low molecular weight heparin).

        Exclusion Criteria:

          -  Prior treatment for myeloma except for one cycle of dexamethasone

          -  History of thromboembolic disease within the past 6 months regardless of
             anticoagulation

          -  Myocardial infarction within 6 months prior to enrollment, or New York Hospital
             Association (NYHA) Class III or IV heart failure (see APPENDIX F), uncontrolled
             angina, severe uncontrolled ventricular arrhythmias, electrocardiographic evidence of
             acute ischemia or active conduction system abnormalities.

          -  Pregnant or breast-feeding women are excluded due to the potential teratogenicity of
             lenalidomide.

          -  Concurrent active malignancy other than non-melanoma skin cancers or carcinoma-insitu
             of the cervix, or presence of myelodysplastic or myeloproliferative disease. Patients
             with prior malignancies with a disease-free interval of ≥ 5 years are eligible.

          -  Patients who have had prior malignancies within the past 5 years but are considered to
             be "cured" with a low likelihood of recurrence may be eligible at the discretion of
             the Principal Investigator.

          -  Active hepatitis B or C infection

          -  HIV 1 or 2 positivity

          -  Any other medical condition or laboratory evaluation that, in the treating physician's
             or principal investigator's opinion, makes the patient unsuitable to participate in
             this clinical trial