Drug/Agent Toxicity by Tissue/Organ, Multiple Myeloma and Plasma Cell Neoplasm
Conditions
Keywords
drug/agent toxicity by tissue/organ, primary systemic amyloidosis
Brief 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.
Detailed description
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.
Interventions
BIOLOGICALfilgrastim
DRUGamifostine trihydrate
DRUGmelphalan
PROCEDUREbone marrow ablation with stem cell support
PROCEDUREperipheral blood stem cell transplantation
Sponsors
National Cancer Institute (NCI)
Eastern Cooperative Oncology Group
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Maximum Tolerated Dose | Assessed over 30 days | The maximum tolerated dose is the highest dose level at which fewer than 1 of 3 or 2 of 6 patients experience dose-limiting toxicity, defined as any grade 3 or higher toxicity of any of the following: renal failure, alkaline phosphatase elevation, GI bleeding, and cardiac rhythm disturbances, assessed using NCI Common Toxicity Criteria, version 2.0. |
Countries
United States
Outcome results
None listed