Samarium Sm 153 Lexidronam Pentasodium Combined With Zoledronic Acid or Pamidronate in Treating Patients With Relapsed or Refractory Multiple Myeloma and Bone Pain

OBJECTIVES:

Primary

- Determine the safety and tolerability of samarium Sm 153 lexidronam pentasodium in
combination with zoledronic acid or pamidronate disodium in patients with relapsed or
refractory multiple myeloma and bone pain. (Phase I)

- Determine the clinical response in patients treated with these regimens. (Phase II)

Secondary

- Determine the effect of these regimens on changes in patient-reported bone pain levels.

OUTLINE: This is a multicenter, open-label, pilot, phase I, dose-escalation study of samarium
Sm 153 lexidronam pentasodium followed by a phase II study.

- Phase I: Patients receive samarium Sm 153 lexidronam pentasodium IV over 1 minute on day
1. Patients also receive zoledronic acid IV over 15 minutes or pamidronate disodium IV
over 2-4 hours on day 1 and then monthly thereafter in the absence of disease
progression or unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses of samarium Sm 153 lexidronam pentasodium
until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose
preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.

- Phase II: Patients receive samarium Sm 153 lexidronam pentasodium at the MTD determined
in phase I and zoledronic acid or pamidronate disodium as in phase I.

Bone pain is assessed periodically.

After completion of study treatment, patients are followed every 3-6 months for up to 3
years.

DISEASE CHARACTERISTICS:

- Diagnosis of multiple myeloma

- Relapsed or refractory disease, meeting 1 of the following criteria:

- Recurrent disease after stem cell transplantation

- Recurrent or progressive disease despite treatment with ≥ 1 standard regimen
(e.g., an alkylating agent plus glucocorticoid and/or the combination of
vincristine, doxorubicin hydrochloride, and dexamethasone)

- Measurable or evaluable disease, defined by at least 1 of the following:

- Monoclonal protein ≥ 1.0 g by serum protein electrophoresis

- Monoclonal protein ≥ 200 mg by 24-hour urine electrophoresis

- Serum immunoglobulin free light chain ≥ 10 mg/dL AND abnormal serum
immunoglobulin kappa to lambda free light chain ratio

- Monoclonal bone marrow plasmacytosis ≥ 30% (evaluable disease)

- Patients must have already undergone hematopoietic stem cell collection, if believed
to be a transplant candidate OR not eligible for a hematopoietic stem cell transplant

PATIENT CHARACTERISTICS:

- ECOG performance status (PS) 0-2 (ECOG PS 3 allowed if secondary to pain)

- ANC ≥ 1,000/mm^3

- Platelet count ≥ 75,000/mm^3

- Hemoglobin ≥ 8.0 g/dL (transfusions allowed)

- Creatinine ≤ 3 mg/dL

- Calcium < 15 mg/dL

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective contraception during and for 4 weeks after
completion of study therapy

- No impending long bone fracture

- No active malignancy except for nonmelanoma skin cancer or carcinoma in situ of the
cervix or breast

- No uncontrolled infection

- No other co-morbidity that would interfere with the patient's ability to participate
in this trial

- No known hypersensitivity to any of the components of samarium Sm 153 lexidronam
pentasodium or bisphosphonates

PRIOR CONCURRENT THERAPY:

- Recovered from all prior surgery, radiotherapy, or other antineoplastic therapy

- More than 4 weeks since prior melphalan or other myelosuppressive agents

- More than 2 weeks since prior nonmyelosuppressive agents (e.g., thalidomide or
high-dose corticosteroids)

- More than 30 days since prior and no other concurrent investigational therapy

- No prior samarium Sm 153 lexidronam pentasodium or strontium chloride Sr 89

- No concurrent external beam radiotherapy

- No concurrent high-dose corticosteroids

- Concurrent chronic steroids (maximum dose of 20 mg/day prednisone equivalent)
allowed for disorders other than myeloma (i.e., adrenal insufficiency or
rheumatoid arthritis)

- Low-dose steroids allowed for replacement or inhalation therapy

- No other concurrent medications, including any of the following:

- Cytotoxic chemotherapy

- Systemic antineoplastic therapy including, but not limited to, immunotherapy,
hormonal therapy, or monoclonal antibody therapy

- Prophylactic hematopoietic growth factors

- Hematopoietic growth factors allowed for established cytopenia therapy