Study to Evaluate Two Lenalidomide Dose Regimens With Low Dose Dexamethasone for the Treatment Relapsed Multiple Myeloma
Condition: Multiple Myeloma
MeSH terms: Multiple Myeloma; Neoplasms, Plasma Cell
Intervention: Lenalidomide 15mg; Lenalidomide 25mg
Intervention description: Subjects will receive oral lenalidomide 15 mg once daily for 1-21 of a 28 day cycle.; Subjects will receive oral lenalidomide 25mg once daily for days 1-21 out of a 28 cycle
Intervention MeSH terms: Lenalidomide
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 33.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Multiple myeloma; Relapsed; Revlimid

Summary:

      This is a research study to evaluate two different Lenalidomide doses (15 mg vs. 25 mg) in
      combination with low dose dexamethasone in patients with relapsed multiple myeloma.

      The investigators propose to use the need for dose reduction as a criterion to judge
      tolerability from various causes. In the veteran population which predominantly is in the
      older age category with number of co-morbidities, a lower dose regimen may be safer and
      advantageous.

      This study expects to enroll approximately 80 subjects from participating VA sites across the
      nation.

      The investigators will evaluate the safety of the two dose regimens by comparing frequency of
      dose reductions. The investigators will also measure how long the responses last with each
      dose.

      Lenalidomide is approved by the Food and Drug Administration (FDA) for the treatment of
      specific types of myelodysplastic syndrome (MDS) and in combination with dexamethasone for
      patients with multiple myeloma (MM) who have received at least 1 prior therapy. MDS and MM
      are cancers of the blood. It is currently being tested in a variety of cancer conditions. In
      this case it is considered experimental.

      At the time of enrollment, one-half of the subjects will be chosen at random to receive the
      15 mg Lenalidomide dose and the other half will take the 25 mg dose regimen of Lenalidomide.
      Depending on lenalidomide treatment assignment, subjects will receive either 15 mg p.o. q.d.
      or 25 mg p.o. q.d. for days 1-21 of a 28 day cycle. In addition, dexamethasone (40 mg) will
      be added once a week (Days 1, 8, 15 and 22) to the Lenalidomide regimen, with a dose
      reduction on the same schedule if the patient cannot tolerate the higher dose of
      dexamethasone. ASA (81 or 325mg) will be given daily for anticoagulation prophylaxis.
      Patients intolerant to ASA may use low molecular weight heparin. Lovenox is recommended.
      Coumadin will be allowed provided the patient is fully anticoagulate with INR 2.0 to 2.5.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Previously diagnosed with multiple myeloma.

          2. Must have relapsed or refractory disease (refractory is defined as progression during
             treatment or within 60 days after the completion of treatment) requiring 2nd or 3rd
             line therapy

          3. Patients may have received lenalidomide and/or dexamethasone

          4. Patients must have measurable disease:

               -  Serum monoclonal protein >0.5g/dL and/or 0.2g/24hr urine light chain excretion

               -  Patients with lower M-protein values or non-secretory myeloma will be eligible if
                  measurable disease can be established, such as serum FreeliteTM chain ratio >5x
                  ULN, measurable soft tissue plasmacytoma >2cm by either physical exam and/or
                  applicable radiographs (i.e. MRI, CT-scan) and/or bone marrow involvement >30%

          5. Age >=18 years at the time of consent.

          6. All necessary baseline studies for determining eligibility must be obtained within 14
             days prior to enrollment. Serum pregnancy tests (sensitivity of at least 25 mIU/mL),
             for females of childbearing potential (WCBP) must be completed. The first test must be
             performed within 10-14 days, and the second test within 24 hours prior to initiation
             of lenalidomide.

          7. Pre-study ECOG performance status 0-2. Patients with lower performance status based
             solely on bone pain will be eligible.

          8. Adequate liver functions: AST and ALT =< 3xULN, alkaline phosphatase =< 3.0x ULN,
             except if attributed to tumor, and bilirubin =< 2xULN.

          9. Have Amylase =< 2.5x ULN

         10. Able to adhere to the study visit schedule and other protocol requirements

         11. Must understand and voluntarily sign an informed consent document.

         12. Females of childbearing potential (FCBP)† must have a negative serum or urine
             pregnancy test with a sensitivity of at least 50 mIU/mL 10 - 14 days prior to and
             again within 24 hours of starting lenalidomide 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 4 weeks 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
             condom if his partner is of child bearing potential. All patients must be counseled at
             a minimum of every 28 days about pregnancy precautions and risks of fetal exposure.

         13. All study participants must be registered into the mandatory RevAssist® program, and
             be willing and able to comply with the requirements of RevAssist®. All counseling will
             be done through RevAssist®.

         14. Able to take aspirin (81 or 325 mg) daily as prophylactic anticoagulation. Patients
             intolerant to ASA may use low molecular weight heparin. Lovenox is recommended.
             Coumadin will be allowed provided the patient is fully anticoagulate with INR 2.0 to
             2.5.

         15. Patients may receive a bisphosphonate.

        Exclusion Criteria:

          1. Any serious medical condition, laboratory abnormality, or psychiatric illness that
             would prevent the subject from signing the informed consent form.

          2. Pregnant or breast feeding females.(Lactating females must agree not to breast feed
             while taking lenalidomide).

          3. Any condition, including the presence of laboratory abnormalities, which places the
             subject at unacceptable risk if he/she were to participate in the study or confounds
             the ability to interpret data from the study.

          4. Renal insufficiency of creatinine clearance <40mL/min

          5. Known hypersensitivity to thalidomide or lenalidomide.

          6. Development of erythema nodosum if characterized by a desquamating rash while taking
             thalidomide or similar drugs.

          7. Concurrent use of other anti-cancer agents or treatments.

          8. Known seropositive for an active viral infection with human immunodeficiency virus
             (HIV), hepatitis B virus (HBV) or hepatitis C virus (HCV). Patients who are
             seropositive because of hepatitis B virus vaccine are eligible.

          9. Has hemoglobin <8.0g/dL. The use of transfusion with pRBC to correct anemia and meet
             eligibility criteria will not be allowed.

         10. Has an absolute neutrophil count <1.0x10^9/L within 14 days before enrollment

         11. Peripheral neuropathy of grade >=3. Patients with painful grade 2 neuropathy are also
             excluded

         12. Has platelet count <75x10^9/L within 14 days before enrollment.

         13. Plasma cell leukemia at time of study entry.