BiRd vs. Rd as Initial Therapy in Multiple Myeloma

This research study is for men and women with newly diagnosed, previously untreated multiple
myeloma. The purpose of this study is to observe the how well the different combinations of
study drugs work as therapy for patients with newly diagnosed, transplant ineligible,
previously untreated multiple myeloma.

The study will be done in two arms:

BiRd Arm:

- Clarithromycin 500mg PO twice daily on days 1-28 for a 28-day cycle

- Lenalidomide 25mg PO daily on days 1-21 of a 28-day cycle

- Dexamethasone 40mg PO will be given on days 1, 8, 15, 22 of a 28-day cycle

Rd Arm:

- Lenalidomide 25mg PO daily on days 1-21 of a 28-day cycle

- Dexamethasone 40mg PO will be given on days 1, 8, 15, 22 of a 28-day cycle

Subjects will be treated in 28-day cycles and may continue treatment as long as they are
responding to therapy and not experiencing unacceptable side effects or disease progression.
There will be an evaluation at the end of each cycle. Participants will be in the study until
disease progression or unacceptable toxicity.

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