amifostine and melphalan in treating patients with primary systemic amyloidosis who are undergoing peripheral stem cell transplantation

Conditions: Drug/Agent Toxicity by Tissue/Organ; Multiple Myeloma and Plasma Cell Neoplasm

Summary: rationale: drugs used in chemotherapy work in different ways to stop the growth of plasma cells, either by killing the cells or by stopping them from dividing. having a peripheral stem cell transplant to replace the blood-forming cells destroyed by chemotherapy, allows higher dose of chemotherapy to be given so that more plasma cells are killed. giving a chemoprotective drug such as amifostine may protect kidney cells from the side effects of chemotherapy. purpose: this phase i trial is studying the side effects and best dose of melphalan given together with amifostine in treating patients who are undergoing peripheral stem cell transplant for primary systemic amyloidosis.

objectives: * determine the maximum tolerated dose (mtd) of high-dose melphalan administered with amifostine in patients with primary systemic amyloidosis undergoing autologous peripheral blood stem cell transplantation. * determine the toxicity of high-dose melphalan when administered at the mtd in these patients. * determine the response rate in patients treated with this regimen. outline: this is a nonrandomized, multicenter, dose-escalation study of melphalan. patients receive filgrastim (g-csf) subcutaneously once daily until peripheral blood stem cell (pbsc) collection is complete. apheresis begins on day 5 of g-csf administration and continues until the target number of pbscs are collected. within 6 weeks of pbsc collection, patients receive amifostine iv over 5 minutes on days -2 and -1 and high-dose melphalan iv over 30-60 minutes on day -1. patients undergo autologous pbsc infusion on day 0. cohorts of 3-6 patients receive escalating doses of melphalan until the maximum tolerated dose (mtd) is determined. the mtd is defined as the dose preceding that at which at least 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. once the mtd is determined, an additional 10 patients are treated at that dose. patients are followed approximately 3 months following transplantation, then every 6 months for 5 years. projected accrual: a total of 3-46 patients will be accrued for this study within 2.3 years.

Eligibility criteria:
disease characteristics: * histologically confirmed amyloidosis * no secondary familial or localized amyloidosis * presence of monoclonal protein by immunoelectrophoresis or immunofixation of serum or urine * no primary amyloidosis manifested only by carpal tunnel syndrome or purpura * amyloid deposits in a plasmacytoma or in bone marrow vessels in an asymptomatic individual not considered an amyloid syndrome * amyloid syndromes include any of the following: * hepatomegaly * cardiomyopathy * nephrotic range proteinuria * peripheral or autonomic neuropathy * no multiple myeloma defined by 1 of the following: * presence of lytic bone disease * more than 30% bone marrow plasma cells patient characteristics: age * 18 to 70 performance status * ecog 0-1 life expectancy * not specified hematopoietic * platelet count at least 100,000/mm\^3 hepatic * see disease characteristics * total or direct bilirubin no greater than 2.0 mg/dl * alkaline phosphatase no greater than 4 times upper limit of normal renal * see disease characteristics * creatinine less than 3.0 mg/dl cardiovascular * see disease characteristics * ejection fraction at least 45% by echocardiogram * no new york heart association class iii or iv heart disease * systolic blood pressure ≥ 90 mmhg other * not pregnant or nursing * negative pregnancy test * fertile patients must use effective contraception * no active infection * no other malignancy within the past 5 years except surgically treated carcinoma in situ of the cervix, nonmelanoma skin cancer, or indolent prostate cancer prior concurrent therapy: biologic therapy * at least 4 weeks since prior interferon chemotherapy * at least 4 weeks since prior melphalan * lifetime total melphalan dose less than 150 mg/m\^2 (based on ideal body weight) endocrine therapy * at least 4 weeks since prior dexamethasone radiotherapy * no prior radiotherapy for amyloidosis surgery * not specified other * no antihypertensive medications for at least 24 hours prior to, during, and for 1 hour after amifostine administration * no other prior treatment

Keywords: drug/agent toxicity by tissue/organ primary systemic amyloidosis