Clinical trial NCT00064337: S0115, High-Dose Melphalan and Autologous Peripheral Stem Cell Transplantation in Treating Patients With Multiple Myeloma or Primary Systemic Amyloidosis
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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Multiple Myeloma
Plasma Cell Myeloma
Keywords: primary systemic amyloidosis
stage II multiple myeloma
stage III multiple myeloma
Lead sponsor: SWOG Cancer Research Network
Sponsor class: NETWORK
Collaborators: name: National Cancer Institute (NCI)
First posted: 2003-07-09
Enrollment: 104
Sex: ALL
Minimum age (years): 18
Maximum age (years): 120
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility 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

Primary outcomes:
measure: Overall Survival
timeFrame: 5 years from initial registration, or until death, whichever occurred earlier, on average, about 4.5 years
Secondary outcomes:
measure: Hematologic Response
timeFrame: Until off study
Other outcomes:
Locations:
city: Little Rock
country: United States
facility: Arkansas Cancer Research Center at University of Arkansas for Medical Sciences
state: Arkansas
city: Sacramento
country: United States
facility: University of California Davis Cancer Center
state: California
city: Boise
country: United States
facility: Mountain States Tumor Institute at St. Luke's Regional Medical Center
state: Idaho
city: Kansas City
country: United States
facility: Kansas Masonic Cancer Research Institute at the University of Kansas Medical Center
state: Kansas
city: Salina
country: United States
facility: Tammy Walker Cancer Center at Salina Regional Health Center
state: Kansas
city: Boston
country: United States
facility: Boston University Cancer Research Center
state: Massachusetts
city: Detroit
country: United States
facility: Barbara Ann Karmanos Cancer Institute
state: Michigan
city: Detroit
country: United States
facility: Josephine Ford Cancer Center at Henry Ford Hospital
state: Michigan
city: Billings
country: United States
facility: CCOP - Montana Cancer Consortium
state: Montana
city: Billings
country: United States
facility: Hematology-Oncology Centers of the Northern Rockies - Billings
state: Montana
city: Billings
country: United States
facility: Northern Rockies Radiation Oncology Center
state: Montana
city: Billings
country: United States
facility: Billings Clinic - Downtown
state: Montana
city: Bozeman
country: United States
facility: Bozeman Deaconess Cancer Center
state: Montana
city: Butte
country: United States
facility: St. James Healthcare Cancer Care
state: Montana
city: Great Falls
country: United States
facility: Big Sky Oncology
state: Montana
city: Great Falls
country: United States
facility: Great Falls Clinic - Main Facility
state: Montana
city: Great Falls
country: United States
facility: Sletten Cancer Institute at Benefis Healthcare
state: Montana
city: Great Falls
country: United States
state: Montana
city: Havre
country: United States
facility: Northern Montana Hospital
state: Montana
city: Helena
country: United States
facility: St. Peter's Hospital
state: Montana
city: Kalispell
country: United States
facility: Glacier Oncology, PLLC
state: Montana
city: Kalispell
country: United States
facility: Kalispell Medical Oncology at KRMC
state: Montana
city: Missoula
country: United States
facility: Guardian Oncology and Center for Wellness
state: Montana
city: Missoula
country: United States
facility: Montana Cancer Specialists at Montana Cancer Center
state: Montana
city: Missoula
country: United States
facility: Montana Cancer Center at St. Patrick Hospital and Health Sciences Center
state: Montana
city: Rochester
country: United States
facility: James P. Wilmot Cancer Center at University of Rochester Medical Center
state: New York
city: Cleveland
country: United States
facility: Cleveland Clinic Taussig Cancer Center
state: Ohio
city: Portland
country: United States
facility: Legacy Good Samaritan Hospital & Comprehensive Cancer Center
state: Oregon
city: Portland
country: United States
facility: Northwest Cancer Specialists at Rose Quarter Cancer Center
state: Oregon
city: Knoxville
country: United States
facility: Thompson Cancer Survival Center
state: Tennessee
city: Seattle
country: United States
facility: Fred Hutchinson Cancer Research Center
state: Washington
city: Seattle
country: United States
facility: Swedish Cancer Institute at Swedish Medical Center - First Hill Campus
state: Washington
city: Seattle
country: United States
facility: University Cancer Center at University of Washington Medical Center
state: Washington
city: Casper
country: United States
facility: Rocky Mountain Oncology
state: Wyoming
city: Sheridan
country: United States
facility: Welch Cancer Center at Sheridan Memorial Hospital
state: Wyoming
Study officials:
affiliation: Boston Medical Center
name: Vaishali Sanchorawala, MD
role: STUDY_CHAIR
affiliation: Boston Medical Center
name: David C. Seldin, MD, PhD
role: STUDY_CHAIR
References: