phase ii study of biaxin, revlimid, and dexamethasone for untreated multiple myeloma

Conditions: Multiple Myeloma

Summary: 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.

Keywords: newly diagnosed multiple myeloma