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

Multiple Myeloma Clinical Trial

Official title:

S0115, A Phase II Trial Evaluating Modified High Dose Melphalan (100 mg/m) And Autologous Peripheral Blood Stem Cell Supported Transplant (SCT) For High Risk Patients With Multiple Myeloma And/Or Light Chain Amyloidosis (AL Amyloidosis) (A BMT Study)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00064337
• Other study ID #: S0115
• Secondary ID: S0115U10CA032102
• Status: Completed
• Phase: Phase 2
• Start date: January 2004
• Est. completion date: November 2015

Study information

• Verified date: July 2018
• Source: Southwest Oncology Group
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 104
• Est. completion date: November 2015
• Est. primary completion date: May 2012
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 120 Years

Eligibility

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

Related Conditions & MeSH terms

• Amyloidosis
• Multiple Myeloma
• Neoplasms, Plasma Cell
• Plasma Cell Myeloma

Intervention

Biological:
• filgrastim

Drug:
• cyclophosphamide

• dexamethasone

• melphalan

• thalidomide

Procedure:
• peripheral blood stem cell transplantation

Locations

Country	Name	City	State
United States	Billings Clinic - Downtown	Billings	Montana
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	Mountain States Tumor Institute at St. Luke's Regional Medical Center	Boise	Idaho
United States	Boston University Cancer Research Center	Boston	Massachusetts
United States	Bozeman Deaconess Cancer Center	Bozeman	Montana
United States	St. James Healthcare Cancer Care	Butte	Montana
United States	Rocky Mountain Oncology	Casper	Wyoming
United States	Cleveland Clinic Taussig Cancer Center	Cleveland	Ohio
United States	Barbara Ann Karmanos Cancer Institute	Detroit	Michigan
United States	Josephine Ford Cancer Center at Henry Ford Hospital	Detroit	Michigan
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	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	Kansas Masonic Cancer Research Institute at the University of Kansas Medical Center	Kansas City	Kansas
United States	Thompson Cancer Survival Center	Knoxville	Tennessee
United States	Arkansas Cancer Research Center at University of Arkansas for Medical Sciences	Little Rock	Arkansas
United States	Guardian Oncology and Center for Wellness	Missoula	Montana
United States	Montana Cancer Center at St. Patrick Hospital and Health Sciences Center	Missoula	Montana
United States	Montana Cancer Specialists at Montana Cancer Center	Missoula	Montana
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	James P. Wilmot Cancer Center at University of Rochester Medical Center	Rochester	New York
United States	University of California Davis Cancer Center	Sacramento	California
United States	Tammy Walker Cancer Center at Salina Regional Health Center	Salina	Kansas
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	Welch Cancer Center at Sheridan Memorial Hospital	Sheridan	Wyoming

Sponsors (2)

Lead Sponsor	Collaborator
Southwest Oncology Group	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Overall Survival	Time from initial registration until death or date of last contact, whichever occurs first, for up to 5 years from the date of the last patient registration.	5 years from initial registration, or until death, whichever occurred earlier, on average, about 4.5 years
Secondary	Hematologic Response		Until off study