BiRd vs. Rd as Initial Therapy in Multiple Myeloma
Condition: Multiple Myeloma
MeSH terms: Multiple Myeloma; Neoplasms, Plasma Cell
Intervention: Clarithromycin; Lenalidomide; Dexamethasone
Intervention description: 500mg PO twice daily on days 1-28 for a 28-day cycle.; 25 mg PO days 1-21 followed by a 7 day rest period for each 28-day cycle; 20 mg PO on Days 1, 8, 15, and 22 for each cycle for subjects 75 years and younger.
Intervention MeSH terms: Clarithromycin; Dexamethasone; Lenalidomide
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 12.0
Sex: All
Minimum age: 65 Years
Healthy volunteers: No

Summary:

      This is a randomized, open-label, phase III study to investigate the efficacy of combination
      therapy with an induction phase utilizing a combination clarithromycin (Biaxin®),
      lenalidomide (Revlimid®), dexamethasone (Decadron®), in multiple myeloma patients who are
      newly diagnosed and require treatment when compared to patients who receive lenalidomide and
      dexamethasone alone.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Subject must voluntarily sign and understand written informed consent.

          -  Subject is at least 65 years old at the time of signing the consent form.

          -  Subject has histologically confirmed multiple myeloma that has never before been
             treated

          -  Subject has no prior anti-myeloma treatment therapy within 14 days prior to initiation
             of study treatment except for corticosteroids with a maximum allowed dosage equivalent
             to three pulses of dexamethasone (40mg daily for 4 days equals one pulse). Patients
             may have received prior adjuvant antiresorptive therapy (i.e., pamidronate or
             zoledronic acid) as routine care, or radiation therapy as palliation for pain and/or
             spinal cord compression.

          -  Subject has measurable disease as defined by > 0.5 g/dL serum monoclonal protein, >10
             mg/dL involved serum free light chain (either kappa or lambda) provided that the serum
             free light chain ratio is abnormal, >0.2 g/24 hrs urinary M-protein excretion, and/or
             measurable plasmacytoma(s) of at least 1cm in greatest dimension as measured by either
             CT scanning or MRI.

          -  Subject has a Karnofsky performance status ≥60% (>50% if due to bony involvement of
             myeloma (see Appendix IV).

          -  Subject is able to take prophylactic anticoagulation as detailed in section 9.1
             (patients intolerant to aspirin may use warfarin or low molecular weight heparin).

          -  Subject is registered into the mandatory RevAssist® program, and is willing and able
             to comply with the requirements of RevAssist® program.

          -  If subject is a female of childbearing potential (FCBP),† she must have a negative
             serum or urine pregnancy test with a sensitivity of at least 25 mIU/mL within 10 - 14
             days prior to and again within 24 hours of prescribing lenalidomide

          -  Subject has a life expectancy ≥ 3 months

          -  Subjects must meet the following laboratory parameters:

               -  Absolute neutrophil count (ANC) ≥750 cells/mm3 (1.0 x 109/L)

               -  Hemoglobin ≥ 7 g/dL

               -  Platelet count ≥ 30,000/mm3 (75 x 109/L)

               -  Serum SGOT/AST <3.0 x upper limits of normal (ULN)

               -  Serum SGPT/ALT <3.0 x upper limits of normal (ULN)

               -  Serum total bilirubin <2.0 mg/dL (34 µmol/L)

               -  Creatinine clearance ≥ 45 cc/min

        Exclusion Criteria:

          -  Subject has immeasurable MM (no measurable monoclonal protein, free light chains in
             blood or urine, or measureable plasmacytoma on radiologic scanning).

          -  Subject has a prior history of other malignancies unless disease free for ≥ 5 years,
             except for basal cell or squamous cell carcinoma of the skin, carcinoma in situ of the
             cervix or breast, or localized prostate cancer with Gleason score < 7 with stable
             prostate specific antigen (PSA) levels.

          -  Subject has had myocardial infarction within 6 months prior to enrollment , or
             NYHA(New York Hospital Association) Class III or IV heart failure (see APPENDIX VI),
             Ejection Fraction < 35%, uncontrolled angina, severe uncontrolled ventricular
             arrhythmias, electrocardiographic evidence of acute ischemia or active conduction
             system abnormalities.

          -  Female subject who is pregnant or lactating.

          -  Subject has known HIV infection

          -  Subject has known active hepatitis B or hepatitis C infection.

          -  Subject has active viral or bacterial infections or any coexisting medical problem
             that would significantly increase the risks of this treatment program.

          -  Subject is unable to reliably take oral medications

          -  Subject has known hypersensitivity to dexamethasone, clarithromycin, lenalidomide, or
             thalidomide

          -  Subject has a history of thromboembolic event within the past 4 weeks prior to
             enrollment.

          -  Subject has any clinically significant medical or psychiatric disease or condition
             that, in the Investigator's opinion, may interfere with protocol adherence or a
             subject's ability to give informed consent.

          -  Subject has previously been treated for multiple myeloma