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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)


Phase 2
18 Years
N/A
Open (Enrolling)
Both
Multiple Myeloma, Plasma Cell Myeloma

Thank you

Trial Information

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)


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.

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

Type of Study:

Interventional

Study Design:

Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Overall survival

Outcome Time Frame:

5 years

Safety Issue:

No

Principal Investigator

Vaishali Sanchorawala, MD

Investigator Role:

Study Chair

Investigator Affiliation:

Boston Medical Center

Authority:

United States: Federal Government

Study ID:

CDR0000315382

NCT ID:

NCT00064337

Start Date:

January 2004

Completion Date:

November 2015

Related Keywords:

  • Multiple Myeloma
  • Plasma Cell Myeloma
  • primary systemic amyloidosis
  • stage II multiple myeloma
  • stage III multiple myeloma
  • Amyloidosis
  • Multiple Myeloma
  • Neoplasms, Plasma Cell

Name

Location

Fred Hutchinson Cancer Research CenterSeattle, Washington  98109
Barbara Ann Karmanos Cancer InstituteDetroit, Michigan  48201
CCOP - Montana Cancer ConsortiumBillings, Montana  59101
Cleveland Clinic Taussig Cancer CenterCleveland, Ohio  44195
University of California Davis Cancer CenterSacramento, California  95817
Arkansas Cancer Research Center at University of Arkansas for Medical SciencesLittle Rock, Arkansas  72205
Kansas Masonic Cancer Research Institute at the University of Kansas Medical CenterKansas City, Kansas  66160-7353
Josephine Ford Cancer Center at Henry Ford HospitalDetroit, Michigan  48202
Swedish Cancer Institute at Swedish Medical Center - First Hill CampusSeattle, Washington  98104
Thompson Cancer Survival CenterKnoxville, Tennessee  37916
James P. Wilmot Cancer Center at University of Rochester Medical CenterRochester, New York  14642
Northern Rockies Radiation Oncology CenterBillings, Montana  59101
Hematology-Oncology Centers of the Northern Rockies - BillingsBillings, Montana  59101
Big Sky OncologyGreat Falls, Montana  59405
St. Peter's HospitalHelena, Montana  59601
Glacier Oncology, PLLCKalispell, Montana  59901
Montana Cancer Center at St. Patrick Hospital and Health Sciences CenterMissoula, Montana  59802
Montana Cancer Specialists at Montana Cancer CenterMissoula, Montana  59802
University Cancer Center at University of Washington Medical CenterSeattle, Washington  98195
Mountain States Tumor Institute at St. Luke's Regional Medical CenterBoise, Idaho  83712-6297
Welch Cancer Center at Sheridan Memorial HospitalSheridan, Wyoming  82801
Tammy Walker Cancer Center at Salina Regional Health CenterSalina, Kansas  67401
Billings Clinic - DowntownBillings, Montana  59107-7000
Bozeman Deaconess Cancer CenterBozeman, Montana  59715
St. James Healthcare Cancer CareButte, Montana  59701
Great Falls Clinic - Main FacilityGreat Falls, Montana  59405
Sletten Cancer Institute at Benefis HealthcareGreat Falls, Montana  59405
Northern Montana HospitalHavre, Montana  59501
Kalispell Medical Oncology at KRMCKalispell, Montana  59901
Legacy Good Samaritan Hospital & Comprehensive Cancer CenterPortland, Oregon  97210
Northwest Cancer Specialists at Rose Quarter Cancer CenterPortland, Oregon  97227
Rocky Mountain OncologyCasper, Wyoming  82609
Great Falls, Montana  59405
Guardian Oncology and Center for WellnessMissoula, Montana  59804
Boston University Cancer Research CenterBoston, Massachusetts  02118