Phase II Study of Biaxin, Revlimid, and Dexamethasone for Untreated Multiple Myeloma

PRIMARY STUDY OBJECTIVES

* To evaluate the efficacy of the combination of clarithromycin (Biaxin®), lenalidomide (Revlimid™), and dexamethasone (Decadron®) as an induction therapy for patients with newly diagnosed multiple myeloma (MM).
* To evaluate the safety of the combination of clarithromycin, lenalidomide, and dexamethasone as an induction therapy for patients with newly diagnosed MM.

SECONDARY STUDY OBJECTIVES

* To examine the role of clarithromycin on the pharmacokinetic properties of dexamethasone and lenalidomide.
* To examine the angiogenesis profile in untreated patients and in patients receiving induction therapy.


Eligibility Criteria:
Inclusion Criteria:

* Subject must voluntarily sign and understand written informed consent.
* Histologically confirmed Durie-Salomon stage II or III MM (see Appendix II). Stage I MM patients will be eligible if they display poor prognostic factors (ß2M \> or = 5.5 mg/L, plasma cell proliferation index \> or = 5%, albumin of less then 3.0, and unfavorable cytogenetics).
* Measurable disease as defined by \> 1.0 g/dL serum monoclonal protein, \>0.1 g/dL serum free light chains, \> 0.2 g/24 hrs urinary M-protein excretion, and/or measurable plasmacytoma(s).
* Age \> or = 18 years at the time of signing the informed consent form.
* Karnofsky performance status \> or = 70% (\>60% if due to bony involvement of myeloma (see Appendix V).
* No prior treatment or less than one full course of first-line therapy. Patients may be receiving adjuvant antiresorptive therapy (i.e., pamidronate or zoledronic acid) as routine care.
* If the patient is a woman of childbearing age, she must have a negative serum or urine pregnancy test within 7 days of starting study.
* Due to the unknown risk of teratogenic side effects, subjects (women and men) must agree to use effective contraception throughout the duration of the study and for at least 1 month after discontinuation of study drugs.
* Life expectancy \> 3 months
* Absolute neutrophil count (ANC)\> or = 1000 cells/mm3 (1.0 x 109/L)
* Platelets count \> or = 75,000/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 creatinine \< 2.5 mg/dL (221 µmol/L)
* Serum total bilirubin \< 2.0 mg/dL (34 µmol/L)

Exclusion Criteria:

* Patients with non-secretory MM (no measurable monoclonal protein, free light chains, and/or M-spike in blood or urine).
* Prior history of other malignancies (except for basal cell or squamous cell carcinoma of the skin or carcinoma in situ of the cervix or breast) unless disease free for ³ 5 years.
* NYHA Class III or IV heart disease. History of active angina, congestive heart disease, or myocardial infarction within 6 months.
* Pregnant or lactating women are ineligible.
* Known HIV positivity
* Active viral or bacterial infections or any coexisting medical problem that would significantly increase the risks of this treatment program.
* Known hypersensitivity to dexamethasone, clarithromycin, lenalidomide, or thalidomide.
* Prior therapy for the treatment of MM
* History of thromboembolic event or other condition currently requiring anticoagulation with warfarin (Coumadin). Patients whose therapy is changed to heparin are eligible.