Celgene High Risk Multiple Myeloma (MM) Revlimid Induction and Maintenance Therapy
Condition: Multiple Myeloma
MeSH terms: Multiple Myeloma; Neoplasms, Plasma Cell
Intervention: Lenalidomide Induction; Sequential Maintenance Therapy
Intervention description: Induction: Lenalidomide 25 mg daily on Days 1-21 followed by 7 day rest and Dexamethasone 40 mg by mouth (po) daily on Days 1, 8, 15 and 22 every 28 days for 4 cycles.; Subjects who achieve >partial response (PR) following induction therapy will receive repeating triplet cycles of alternating low dose therapy until progression, poor tolerance or toxicity. Subjects who complete 24 months of maintenance will be removed from study unless they achieved > stable disease (SD) from maintenance (per discussion with physician):
325 mg aspirin for deep vein thrombosis (DVT) prophylaxis
Cycle 1, 4, 7, etc. - bortezomib 1.3 mg/m2 on day 1 and 8 of a 28-day cycle
Cycle 2, 5, 8 etc. - Melphalan 6 mg/m2 by mouth (po) daily on Days 1-7
Prednisone 60 mg /m2 po daily on Days 1-7 of a 28-day cycle
Cycle 3, 6, 9, etc. Lenalidomide 10 mg po daily on Days 1-21 of a 28 day cycle.
Intervention MeSH terms: Prednisone; Lenalidomide; Bortezomib; Melphalan
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 18.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Multiple Myeloma

Summary:

      The purpose of this study is to evaluate the effectiveness of induction therapy with
      lenalidomide and low dose dexamethasone followed by sequential low dose bortezomib followed
      by low dose Melphalan and Prednisone, then followed by low dose lenalidomide for multiple
      cycles in subjects with high risk Multiple Myeloma (MM). The primary objective is to evaluate
      the efficacy as measured by the progression free survival (PFS) at 2 years of low dose
      sequential therapy following four cycles of induction therapy with lenalidomide/low-dose
      dexamethasone in subjects with symptomatic high risk multiple myeloma, who have received no
      prior treatment. A total of 35 subjects were estimated to be accrued to this Phase II trial
      over a period of subjects who are still progression-free at 2 years. Two years will be as
      measured from date of registration to the trial. Progression will include disease progression
      (DP) as well as death due to any cause. Data will be analyzed and reported by the PI after 1
      and 2 years of initiation of the study. All subsequent data collected may be analyzed and
      reported in a follow-up clinical report. The PI and independent reviewers will meet to review
      the efficacy and safety data and determine a risk/benefit analysis in this subject
      population.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Understand and voluntarily sign an informed consent form.

          2. Age 18 years or older at the time of signing the consent.

          3. Able to adhere to the study visit schedule and other protocol requirements.

          4. Multiple myeloma (MM) diagnosed according to the following standard criteria:

               -  Monoclonal plasma cells in bone marrow ≥10% and/or presence of biopsy-proven
                  plasmacytoma

               -  Monoclonal protein present in serum and/or urine Myeloma-related organ
                  dysfunction (1 or more) (C) Calcium elevation in blood (serum calcium >10.5 mg/L
                  or ULN) (R) Renal insufficiency (SCr >2 mg/dL) (A) Anemia (hemoglobin <10 g/dL or
                  2g <normal) (B) Lytic bone lesions or osteoporosis

          5. Measurable disease requiring systemic therapy.

          6. High risk multiple myeloma defined by the presence of one or more of the following:

               -  Deletion of chromosome 13 by metaphase analysis (standard cytogenetics)

               -  deletion of 17p13 (p53) by Fluorescence in situ hybridization (FISH) or metaphase
                  analysis

               -  t(4;14) by FISH

               -  t(14;16) by FISH

               -  t(8;14) by FISH

               -  t(14;20) by FISH

               -  hypodiploidy detected by FISH or metaphase analysis

               -  any complex cytogenetic abnormality detected by metaphase analysis, with the
                  exception of hyperdiploidy

          7. No previous treatment with systemic therapy or radiation therapy lasting more than 4
             weeks duration.

          8. At least 7 days since date of last radiation or systemic treatment for MM.

          9. Eastern Cooperative Oncology Group (ECOG) performance status of < or =2 at study
             entry.(0=Fully active; 1=Restricted but ambulatory; 2=Ambulatory but unable to work)

         10. All study participants must be registered into the mandatory RevAssist® program, and
             willing and able to comply with the requirements.

         11. Females of childbearing potential (FCBP) must have negative pregnancy test with a
             sensitivity of >/=50 milli-International unit (mIU)/mL within 10-14 days prior to and
             within 24 hours of prescribing lenalidomide and must use 2 acceptable methods of birth
             control, one highly effective method and one other effective method AT THE SAME TIME,
             >4 weeks before 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 even if
             he has had a successful vasectomy, if partner is FCBP.

         12. Disease free of prior malignancies for >5 years with exception of currently treated
             basal cell, squamous cell carcinoma of the skin, or carcinoma "insitu" of the cervix
             or breast

         13. Able to take 325 mg aspirin daily as prophylactic anticoagulation for the duration of
             protocol therapy.

         14. Receive concomitant therapy with bisphosphonates if bony lesions are present at time
             of enrollment.

        Exclusion criteria

          1. Any serious medical condition, laboratory abnormality, or psychiatric illness to
             prevent the subject from signing the consent.

          2. Pregnant or breast feeding females.

          3. Any condition which places the subject at unacceptable risk or confounds the ability
             to interpret data from the study.

          4. Abnormal laboratory test results within these ranges:

               -  Absolute neutrophil count < 1.0 x 109/L

               -  Platelet count < 50 x 109/L (Subjects with severe pancytopenia (not meeting the
                  above criteria) due to myeloma involvement of > 70% bone marrow are eligible)

               -  Serum creatinine > 2.5 mg/dL or ≥ 3.0 mg/dL if due to multiple myeloma.

               -  Total bilirubin > 2.0 mg/dl

          5. History of allergy to any of the study medications, their analogues, or excipients in
             the various formulations

          6. Concurrent use of other anti-cancer agents or treatments.

          7. Known HIV positivity

          8. Known Active Hepatitis A, B or C

          9. Erythema nodosum characterized by a desquamating rash while taking thalidomide or
             similar drug.