Clinical trial NCT00003353: High-Dose Melphalan Plus Peripheral Stem Cell Transplantation in Treating Patients With Primary Systemic Amyloidosis
Official title: A Phase II Study of High-Dose Melphalan With Hematopoietic Stem Cell Reconstitution for Patients With Primary Systemic Amyloidosis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Multiple Myeloma and Plasma Cell Neoplasm
Keywords: primary systemic amyloidosis
Lead sponsor: Eastern Cooperative Oncology Group
Sponsor class: NETWORK
Collaborators: name: National Cancer Institute (NCI)
First posted: 2004-09-13
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Primary purpose: TREATMENT

Brief summary: RATIONALE: High-dose chemotherapy may destroy the amyloid-producing cells in bone marrow. Peripheral stem cell transplantation

PURPOSE: Phase II trial to study the effectiveness of high dose melphalan plus peripheral stem cell transplantation in treating patients who have primary systemic amyloidosis.

Detailed description: OBJECTIVES: I. Assess the response rate and overall survival of patients with biopsy proven primary amyloidosis following treatment with myeloablative chemotherapy and hematopoietic stem cell reconstitution. II. Evaluate the toxicity of high dose melphalan in this patient population.

OUTLINE: Patients receive filgrastim (G-CSF) subcutaneously daily beginning on day 1 of the peripheral blood stem cell (PBSC) collection period and continuing until PBSC collection is completed. PBSC are collected beginning on day 5 of the collection period and continuing until the final target cell count is reached or for up to a maximum of 7 collections. If sufficient PBSCs are not harvested within a maximum of 7 collections, the patient is removed from the study. Within 30 days of PBSC collection, patients receive melphalan IV on day -1 of the infusion period and PBSC infusion on day 0. The infusion period continues until day 30. Patients receive G-CSF subcutaneously daily starting on day 1 and continuing until blood counts recover. Patients are followed every 3 months for 2 years, every 3 months for 3 additional years, and yearly thereafter.

PROJECTED ACCRUAL: A maximum of 33 patients will be accrued for this study over 2 years.

Eligibility criteria: DISEASE CHARACTERISTICS: Histologically confirmed primary amyloidosis Must have presence of paraprotein in serum or urine determined by immunoelectrophoresis/immunofixation No primary amyloidosis manifested only by carpal tunnel syndrome or purpura No history of secondary, familial, or localized amyloidosis No evidence of overt multiple myeloma: Lytic bone disease or pathological fractures OR At least 30% plasma cells in bone marrow

PATIENT CHARACTERISTICS: Age: 18 to 70 Performance status: ECOG 0-2 Life expectancy: Not specified Hematopoietic: Absolute granulocyte count at least 1000/mm3 Platelet count at least 100,000/mm3 Hepatic: Bilirubin no greater than 2.0 mg/dL Alkaline phosphatase no greater than 1000 u/L or less than 4 times upper limit of normal Renal: Creatinine no greater than 2.0 mg/dL Cardiovascular: Confirmed by echocardiogram: Ejection fraction at least 50% Interventricular septal thickness no greater than 15 mm No New York Heart Association classification II-IV Pulmonary: DLCO at least 50% FVC at least 60% FEV1 at least 55% 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 No known sensitivity to E. coli derivatives

PRIOR CONCURRENT THERAPY: Biologic therapy: Prior interferon allowed Chemotherapy: At least 4 weeks since prior melphalan Lifetime cumulative dose of melphalan no greater than 150 mg No greater than 2 prior courses of chemotherapy Endocrine therapy: Prior dexamethasone allowed Radiotherapy: Not specified Surgery: Not specified

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
city: Scottsdale
country: United States
facility: CCOP - Scottsdale Oncology Program
state: Arizona
city: Miami
country: United States
facility: Sylvester Cancer Center, University of Miami
state: Florida
city: Tampa
country: United States
facility: H. Lee Moffitt Cancer Center and Research Institute
state: Florida
city: Evanston
country: United States
facility: CCOP - Evanston
state: Illinois
city: Peoria
country: United States
facility: CCOP - Illinois Oncology Research Association
state: Illinois
city: Indianapolis
country: United States
facility: Indiana University Cancer Center
state: Indiana
city: Indianapolis
country: United States
facility: Veterans Affairs Medical Center - Indianapolis (Roudebush)
state: Indiana
city: Boston
country: United States
facility: New England Medical Center Hospital
state: Massachusetts
city: Rochester
country: United States
facility: Mayo Clinic Cancer Center
state: Minnesota
city: Saint Louis Park
country: United States
facility: CCOP - Metro-Minnesota
state: Minnesota
city: Rochester
country: United States
facility: University of Rochester Cancer Center
state: New York
city: Cleveland
country: United States
facility: Ireland Cancer Center
state: Ohio
city: Nashville
country: United States
facility: Veterans Affairs Medical Center - Nashville
state: Tennessee
city: Nashville
country: United States
facility: Vanderbilt Cancer Center
state: Tennessee
city: Marshfield
country: United States
facility: CCOP - Marshfield Medical Research and Education Foundation
state: Wisconsin
city: Milwaukee
country: United States
facility: Medical College of Wisconsin
state: Wisconsin
city: Milwaukee
country: United States
facility: Veterans Affairs Medical Center - Milwaukee (Zablocki)
state: Wisconsin
Study officials:
affiliation: Mayo Clinic
name: Morie A. Gertz, MD
role: STUDY_CHAIR
References:
citation: Gertz MA, Blood E, Vesole DH, Abonour R, Lazarus HM, Greipp PR. A multicenter phase 2 trial of stem cell transplantation for immunoglobulin light-chain amyloidosis (E4A97): an Eastern Cooperative Oncology Group Study. Bone Marrow Transplant. 2004 Jul;34(2):149-54. doi: 10.1038/sj.bmt.1704539.