Zoledronic Acid in the Management of Patients With Asymptomatic/Early Stage Multiple Myeloma

A Randomized Phase II Study of Bisphosphonate: Zoledronic Acid (Zometa) in the Management of Asymptomatic/Early Stage Multiple Myeloma: Hoosier Oncology Group MM02-35

Evidence for the beneficial effects of bisphosphonates on bone resorption in multiple myeloma has been reported extensively, showing reductions in skeletal events and improvement of several biochemical variables in bone resorption. Zoledronic acid (Zometa®, CGP42446) is the most potent clinically available bisphosphonates, with the largest therapeutic ratio between the desired inhibition of calcium resorption and the unwanted inhibition of mineralization in vitro of all the bisphosphonates.

This trial will investigate the efficacy of zoledronic acid in preventing skeletal events in patients with asymptomatic/early stage Multiple Myeloma

OUTLINE: This is a multi-center study.

• Patients will be randomly assigned by study number to receive 4mg of zoledronic acid every three months or to be observed.

Performance status: ECOG performance status 0-3 (KPS 30 - 100)

Life expectancy: 12 months

Hematopoietic:

• Hb >10 g/dl within 14 days prior to registration

Hepatic:

• Not specified

Renal:

• Serum creatinine < 2 mg/dl within 14 days prior to registration

Cardiovascular:

• Not specified

Pulmonary:

• Not specified

Inclusion Criteria:

• Diagnosis of asymptomatic multiple myeloma as defined by the criteria below:
• Presence of bone marrow clonal plasma cells (more than 10%)
• Presence of an M-protein in serum and/or urine (no concentration specified)
• Serum calcium < 12 mg/dl within 14 days prior to registration. Less than 3 lytic lesions, no pathologic fractures and no osteopenia noted on skeletal survey
• No symptoms of hyperviscosity, amyloidosis or recurrent infection
• Bone mineral density with a T score higher than -2.0 standard deviation (not have osteoporosis) within 28 days prior to registration
• Negative pregnancy test

Exclusion Criteria:

• No previous treatment with bisphosphonates
• No disorders of the parathyroid or thyroid glands
• No current breastfeeding
• No prior malignancy is allowed except for adequately treated in situ cervical cancer, Gleason < grade 7 prostate cancers