S0115, High-Dose Melphalan and Autologous Peripheral Stem Cell Transplantation in Treating Patients With Multiple Myeloma or Primary Systemic Amyloidosis

NCT ID: NCT00064337

Last Updated: 2018-08-09

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 104 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2004-01-31
• Study Completion Date: 2015-11-30

Brief Summary

RATIONALE: Drugs used in chemotherapy such as melphalan work in different ways to stop cancer cells from dividing so they stop growing or die. Combining chemotherapy with donor peripheral stem cell transplantation may allow the doctor to give higher doses of chemotherapy drugs and kill more cancer cells.

PURPOSE: This phase II trial is studying how well giving melphalan together with autologous stem cell transplantation works in treating patients with multiple myeloma or primary systemic amyloidosis.

Detailed Description

OBJECTIVES:

• Determine overall survival of patients with high-risk multiple myeloma, primary systemic amyloidosis, or light chain deposition disease treated with two courses of modified high-dose melphalan and autologous peripheral blood stem cell transplantation.
• Determine the hematologic response in patients treated with this regimen.
• Determine the qualitative and quantitative toxic effects of this regimen in these patients.
• Determine the prognostic significance of cytogenetic markers in these patients.

OUTLINE: This is a multicenter study. Patients are stratified according to disease (high-risk multiple myeloma vs primary systemic amyloidosis vs both).

• Induction therapy (multiple myeloma patients only): Patients receive oral dexamethasone on days 1-4, 9-12, and 17-20 and oral thalidomide daily on days 1-35. Treatment repeats every 35 days for 2 courses in the absence of disease progression or unacceptable toxicity.
• Mobilization and stem cell collection:

• Multiple myeloma patients: Within 28-35 days after completion of induction therapy, patients receive cyclophosphamide IV over 2-3 hours on day 1 and filgrastim (G-CSF) subcutaneously (SC) daily beginning on day 2 and continuing through the day before the last leukapheresis. Usage of mesna IV on day 1 (prior to and twice after cyclophosphamide administration is recommended).
• Primary systemic amyloidosis patients: Patients receive G-CSF SC daily beginning on day 1 and continuing through the day before the last leukapheresis.

All patients undergo leukapheresis for the collection of stem cells until the target number of CD34+ cells is reached.

• Conditioning regimen: Within 1-4 weeks after mobilization, patients receive modified high-dose melphalan IV over 20 minutes on day -2.
• Peripheral blood stem cell (PBSC) reinfusion: PBSCs are reinfused on day 0. Patients receive G-CSF SC daily beginning on day 1 and continuing until blood counts recover.

Patients undergo a second autologous PBSC transplantation within 3-6 months, but no later than 12 months, after the first transplantation.

• Second conditioning regimen: Patients receive modified high-dose melphalan IV over 20 minutes on day -2.
• Second PBSC infusion: PBSCs are infused on day 0.
• Maintenance regimen (multiple myeloma patients only): Between 4-8 weeks after the second transplantation, patients with no progressive disease receive oral dexamethasone once daily on days 1-4 and oral thalidomide once daily on days 1-28. Courses repeat every 28 days for 2 years in the absence of disease progression or unacceptable toxicity.

Patients are followed at 3 and 6 months and then annually thereafter.

PROJECTED ACCRUAL: A total of 100 patients will be accrued for this study within 20-25 months.

Conditions

Multiple Myeloma; Plasma Cell Myeloma

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Treatment

MM Induction: dexamethasone 20mg/d PO Days 1-4, 9-12 and 17-20 every 35 days for 2 cycles and thalidomide 200 mg/d PO Days 1-70.

Mobilization and SC Collection:

MM, MM+AL, MM+LCD: cyclophosphamide 2.5 gm/m2 IV Day 1; mesna 800 mg/m2 IV Day 1 x 3 doses; G-CSF 10 mcg/kg/d SQ Day 2 through day prior to last leukapheresis.

Amyloid or LCDD-Only: G-CSF 16 mcg/kg/d SQ Days 1-3 (continued daily until the day prior to the last day of stem cell collection).

Conditioning/Transplant - Modified HighDose Melphalan (given for both transplants): melphalan 100 mg/m2/d IV over 20 mins Day -2; PBSC infusion >/= 3.5 x 10^6 CD34+ cells/kg IV Day 0.

Maintenance (MM only): dexamethasone 40 mg/d PO Days 1-4 every 28 days and thalidomide 100 mg/d PO daily - given for one year, followed by dexamethasone 40 mg/d PO Days 1-4 every 28 days and thalidomide 100 mg/d PO daily - given for one year.

Group Type: EXPERIMENTAL

filgrastim

Intervention Type: BIOLOGICAL

cyclophosphamide

Intervention Type: DRUG

dexamethasone

Intervention Type: DRUG

melphalan

Intervention Type: DRUG

thalidomide

Intervention Type: DRUG

peripheral blood stem cell transplantation

Intervention Type: PROCEDURE

Interventions

filgrastim

Intervention Type: BIOLOGICAL

cyclophosphamide

Intervention Type: DRUG

dexamethasone

Intervention Type: DRUG

melphalan

Intervention Type: DRUG

thalidomide

Intervention Type: DRUG

peripheral blood stem cell transplantation

Intervention Type: PROCEDURE

Eligibility Criteria

Inclusion Criteria

DISEASE CHARACTERISTICS:

• At least 1 of the following diagnoses:

• Multiple myeloma

• Stage II or III disease
• At least 1 of the following must be present:

• Serum M-protein of IgG, IgA, IgD, IgE greater than 1.0 g/dL
• Urinary M-protein (Bence-Jones) at least 200 mg/24 hours
• No IgM peaks except in patients who have physiologic criteria to support a diagnosis of multiple myeloma (e.g., bony lesions, myeloma kidney-cast nephropathy, absence of adenopathy [unless pathology-proven to be plasma cell infiltration])
• No monoclonal gammopathy of undetermined significance
• No indolent or smoldering myeloma
• No disease progression on prior thalidomide or dexamethasone
• Histologically confirmed primary systemic amyloidosis

• No senile, secondary, localized, dialysis-related, or familial amyloidosis
• No severe cardiac involvement

• No pre-exertional syncope, ventricular arrhythmia, or symptomatic pleural effusions associated with cardiac involvement
• Light Chain Deposition Disease alone or in combination with multiple myeloma meeting the following criteria:

• Deposition of granular material containing free light chains/immunoglobulins that did not bind Congo red
• Evidence of plasma cell dyscrasia (i.e., monoclonal gammopathy in the serum or urine by immunofixation electrophoresis and/or clonal plasmacytosis) on bone marrow biopsy by immunohistochemistry and/or elevated serum-free light chain concentration
• Must have been diagnosed within the past year
• Concurrent enrollment in the myeloma repository protocol SWOG-S0309 must be offered

PATIENT CHARACTERISTICS:

Age

• 18 and over (patients with amyloidosis only OR patients with amyloidosis and multiple myeloma OR patients with multiple myeloma only with poor renal function) OR
• 70 and over (patients with multiple myeloma only with or without poor renal function)

Performance status

• Zubrod 0-2

Life expectancy

• Not specified

Hematopoietic

• Absolute neutrophil count at least 1,000/mm^3
• Platelet count at least 100,000/mm^3

Hepatic

• Bilirubin no greater than 2.5 times upper limit of normal (ULN)
• SGOT or SGPT no greater than 2.5 times ULN

Renal

• No hemodialysis within 2 hours of melphalan or stem cell infusion

Cardiovascular

• See Disease Characteristics
• Hemodynamically stable (i.e., systolic blood pressure > 90 mm Hg in a lying position within the past 42 days)
• No myocardial infarction within the past 6 months
• No congestive heart failure
• No arrhythmia refractory to medical therapy
• LVEF greater than 45% by echocardiogram or MUGA

Pulmonary

• See Disease Characteristics
• No history of chronic obstructive or chronic restrictive pulmonary disease
• Pulmonary function studies (e.g., FEV_1 and FVC) at least 50% of predicted
• DLCO at least 50% of predicted
• Normal high resolution CT scan of the chest and acceptable arterial blood gases (i.e., PO_2 greater than 70) required for patients unable to complete pulmonary function tests due to bone pain or fracture

Other

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception

• Multiple myeloma patients receiving thalidomide must use 2 methods of effective contraception for at least 4 weeks before, during, and for at least 4 weeks after discontinuation of thalidomide
• HIV negative
• No other concurrent significant medical condition
• No concurrent uncontrolled life-threatening infection
• No other malignancy within the past 5 years except adequately treated basal cell or squamous cell skin cancer, carcinoma in situ of the cervix, or adequately treated stage I or II cancer currently in complete remission

PRIOR CONCURRENT THERAPY:

Biologic therapy

• See Disease Characteristics

Chemotherapy

• See Disease Characteristics
• Prior cumulative melphalan dose no more than 200 mg
• No other concurrent chemotherapy

Endocrine therapy

• See Disease Characteristics
• No concurrent hormonal therapy

Radiotherapy

• No concurrent radiotherapy

Surgery

• Not specified

Other

• Recovered from prior therapy
• Prior or concurrent bisphosphonates allowed

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 120 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

SWOG Cancer Research Network

NETWORK

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Vaishali Sanchorawala, MD

Role: STUDY_CHAIR

Boston Medical Center

David C. Seldin, MD, PhD

Role: STUDY_CHAIR

Boston Medical Center

Locations

Arkansas Cancer Research Center at University of Arkansas for Medical Sciences

Little Rock, Arkansas, United States

University of California Davis Cancer Center

Sacramento, California, United States

Mountain States Tumor Institute at St. Luke's Regional Medical Center

Boise, Idaho, United States

Kansas Masonic Cancer Research Institute at the University of Kansas Medical Center

Kansas City, Kansas, United States

Tammy Walker Cancer Center at Salina Regional Health Center

Salina, Kansas, United States

Boston University Cancer Research Center

Boston, Massachusetts, United States

Barbara Ann Karmanos Cancer Institute

Detroit, Michigan, United States

Josephine Ford Cancer Center at Henry Ford Hospital

Detroit, Michigan, United States

CCOP - Montana Cancer Consortium

Billings, Montana, United States

Hematology-Oncology Centers of the Northern Rockies - Billings

Billings, Montana, United States

Northern Rockies Radiation Oncology Center

Billings, Montana, United States

Billings Clinic - Downtown

Billings, Montana, United States

Bozeman Deaconess Cancer Center

Bozeman, Montana, United States

St. James Healthcare Cancer Care

Butte, Montana, United States

Big Sky Oncology

Great Falls, Montana, United States

Great Falls Clinic - Main Facility

Great Falls, Montana, United States

Sletten Cancer Institute at Benefis Healthcare

Great Falls, Montana, United States

Great Falls, Montana, United States

Northern Montana Hospital

Havre, Montana, United States

St. Peter's Hospital

Helena, Montana, United States

Glacier Oncology, PLLC

Kalispell, Montana, United States

Kalispell Medical Oncology at KRMC

Kalispell, Montana, United States

Guardian Oncology and Center for Wellness

Missoula, Montana, United States

Montana Cancer Specialists at Montana Cancer Center

Missoula, Montana, United States

Montana Cancer Center at St. Patrick Hospital and Health Sciences Center

Missoula, Montana, United States

James P. Wilmot Cancer Center at University of Rochester Medical Center

Rochester, New York, United States

Cleveland Clinic Taussig Cancer Center

Cleveland, Ohio, United States

Legacy Good Samaritan Hospital & Comprehensive Cancer Center

Portland, Oregon, United States

Northwest Cancer Specialists at Rose Quarter Cancer Center

Portland, Oregon, United States

Thompson Cancer Survival Center

Knoxville, Tennessee, United States

Fred Hutchinson Cancer Research Center

Seattle, Washington, United States

Swedish Cancer Institute at Swedish Medical Center - First Hill Campus

Seattle, Washington, United States

University Cancer Center at University of Washington Medical Center

Seattle, Washington, United States

Rocky Mountain Oncology

Casper, Wyoming, United States

Welch Cancer Center at Sheridan Memorial Hospital

Sheridan, Wyoming, United States

Countries

United States

Other Identifiers

S0115

Identifier Type: OTHER

Identifier Source: secondary_id

U10CA032102

Identifier Type: NIH

Identifier Source: secondary_id

View Link

S0115

Identifier Type: -

Identifier Source: org_study_id