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

Sponsor:	Southwest Oncology Group
Collaborator:	National Cancer Institute (NCI)
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00064337

Purpose

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.

Condition	Intervention	Phase
Multiple Myeloma and Plasma Cell Neoplasm	Biological: filgrastim Drug: cyclophosphamide Drug: dexamethasone Drug: melphalan Drug: thalidomide Procedure: peripheral blood stem cell transplantation	Phase II

Study Type:	Interventional
Study Design:	Treatment, Open Label
Official Title:	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)

Resource links provided by NLM:

Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:

Overall survival [ Designated as safety issue: No ]

Secondary Outcome Measures:

Hematologic response [ Designated as safety issue: No ]
Qualitative and quantitative toxicity [ Designated as safety issue: Yes ]
Prognostic significance of cytogenetic markers [ Designated as safety issue: No ]

Estimated Enrollment:	100
Study Start Date:	January 2004
Estimated Primary Completion Date:	July 2014 (Final data collection date for primary outcome measure)

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

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00064337

Show 67 Study Locations

Sponsors and Collaborators

Southwest Oncology Group

National Cancer Institute (NCI)

Investigators

Investigator:	Vaishali Sanchorawala, MD	Boston Medical Center
Investigator:	David C. Seldin, MD, PhD	Boston Medical Center

More Information

Additional Information:

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

No publications provided

Responsible Party:	Southwest Oncology Group - Group Chair's Office ( Laurence H. Baker )
Study ID Numbers:	CDR0000315382, SWOG-S0115
Study First Received:	July 8, 2003
Last Updated:	November 7, 2009
ClinicalTrials.gov Identifier:	NCT00064337 History of Changes
Health Authority:	Unspecified

Keywords provided by National Cancer Institute (NCI):

primary systemic amyloidosis
stage II multiple myeloma
stage III multiple myeloma

Additional relevant MeSH terms:

Dexamethasone
Anti-Inflammatory Agents
Anti-Infective Agents
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs
Hormones, Hormone Substitutes, and Hormone Antagonists
Antiemetics
Hormones
Hemorrhagic Disorders
Therapeutic Uses
Cardiovascular Diseases
Angiogenesis Modulating Agents
Immunoproliferative Disorders
Metabolic Diseases
Immune System Diseases

Antineoplastic Agents, Hormonal
Hematologic Diseases
Glucocorticoids
Multiple Myeloma
Neoplasms
Leprostatic Agents
Melphalan
Immunologic Factors
Thalidomide
Blood Protein Disorders
Antineoplastic Agents
Paraproteinemias
Cyclophosphamide
Hemostatic Disorders
Anti-Bacterial Agents

ClinicalTrials.gov processed this record on November 27, 2009