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

NCT00064337 | Completed Phase 2 Results DMC

• 2 other identifiers: S0115U10CA032102
• Study Type: interventional
• Target: 104
• Locations: 1 country
• Sites: 35

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.

Conditions

Multiple Myeloma; Plasma Cell Myeloma

Keywords

primary systemic amyloidosis; stage II multiple myeloma; stage III multiple myeloma

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (1)

• Hematologic Response

  Until off study

Study Arms (1)

Treatment

EXPERIMENTAL

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.

Biological: filgrastim; Drug: cyclophosphamide; Drug: dexamethasone; Drug: melphalan; Drug: thalidomide; Procedure: peripheral blood stem cell transplantation

Interventions

filgrastim BIOLOGICAL

Treatment

cyclophosphamide DRUG

Treatment

dexamethasone DRUG

Treatment

melphalan DRUG

Treatment

thalidomide DRUG

Treatment

peripheral blood stem cell transplantation PROCEDURE

Treatment

Eligibility Criteria

• Age: 18 Years - 120 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

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

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• SWOG Cancer Research Network: lead
• National Cancer Institute (NCI): collaborator

Study Sites (35)

Arkansas Cancer Research Center at University of Arkansas for Medical Sciences

Little Rock, Arkansas, 72205, United States

Location

University of California Davis Cancer Center

Sacramento, California, 95817, United States

Location

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

Boise, Idaho, 83712, United States

Location

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

Kansas City, Kansas, 66160-7357, United States

Location

Tammy Walker Cancer Center at Salina Regional Health Center

Salina, Kansas, 67401, United States

Location

Boston University Cancer Research Center

Boston, Massachusetts, 02118, United States

Location

Barbara Ann Karmanos Cancer Institute

Detroit, Michigan, 48201-1379, United States

Location

Josephine Ford Cancer Center at Henry Ford Hospital

Detroit, Michigan, 48202, United States

Location

CCOP - Montana Cancer Consortium

Billings, Montana, 59101, United States

Location

Hematology-Oncology Centers of the Northern Rockies - Billings

Billings, Montana, 59101, United States

Location

Northern Rockies Radiation Oncology Center

Billings, Montana, 59101, United States

Location

Billings Clinic - Downtown

Billings, Montana, 59107-7000, United States

Location

Bozeman Deaconess Cancer Center

Bozeman, Montana, 59715, United States

Location

St. James Healthcare Cancer Care

Butte, Montana, 59701, United States

Location

Big Sky Oncology

Great Falls, Montana, 59405-5309, United States

Location

Great Falls Clinic - Main Facility

Great Falls, Montana, 59405, United States

Location

Sletten Cancer Institute at Benefis Healthcare

Great Falls, Montana, 59405, United States

Location

Unknown Facility

Great Falls, Montana, 59405, United States

Location

Northern Montana Hospital

Havre, Montana, 59501, United States

Location

St. Peter's Hospital

Helena, Montana, 59601, United States

Location

Glacier Oncology, PLLC

Kalispell, Montana, 59901, United States

Location

Kalispell Medical Oncology at KRMC

Kalispell, Montana, 59901, United States

Location

Guardian Oncology and Center for Wellness

Missoula, Montana, 59804, United States

Location

Montana Cancer Specialists at Montana Cancer Center

Missoula, Montana, 59807-7877, United States

Location

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

Missoula, Montana, 59807, United States

Location

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

Rochester, New York, 14642, United States

Location

Cleveland Clinic Taussig Cancer Center

Cleveland, Ohio, 44195, United States

Location

Legacy Good Samaritan Hospital & Comprehensive Cancer Center

Portland, Oregon, 97210, United States

Location

Northwest Cancer Specialists at Rose Quarter Cancer Center

Portland, Oregon, 97227, United States

Location

Thompson Cancer Survival Center

Knoxville, Tennessee, 37916, United States

Location

Fred Hutchinson Cancer Research Center

Seattle, Washington, 98109, United States

Location

Swedish Cancer Institute at Swedish Medical Center - First Hill Campus

Seattle, Washington, 98122-4307, United States

Location

University Cancer Center at University of Washington Medical Center

Seattle, Washington, 98195, United States

Location

Rocky Mountain Oncology

Casper, Wyoming, 82609, United States

Location

Welch Cancer Center at Sheridan Memorial Hospital

Sheridan, Wyoming, 82801, United States

Location

MeSH Terms

Conditions

Multiple Myeloma; Immunoglobulin Light-chain Amyloidosis

Interventions

Filgrastim; Cyclophosphamide; Dexamethasone; Melphalan; Thalidomide; Peripheral Blood Stem Cell Transplantation

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases; Amyloidosis; Proteostasis Deficiencies; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Granulocyte Colony-Stimulating Factor; Colony-Stimulating Factors; Glycoproteins; Glycoconjugates; Carbohydrates; Hematopoietic Cell Growth Factors; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated; Phenylalanine; Amino Acids, Aromatic; Amino Acids, Cyclic; Amino Acids; Phthalimides; Phthalic Acids; Acids, Carbocyclic; Carboxylic Acids; Piperidones; Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Isoindoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Hematopoietic Stem Cell Transplantation; Stem Cell Transplantation; Cell Transplantation; Cell- and Tissue-Based Therapy; Biological Therapy; Therapeutics; Transplantation; Surgical Procedures, Operative

Results Point of Contact

• Title: Study Statistician
• Organization: SWOG Statistical Center

206-667-4623

Study Officials

• Vaishali Sanchorawala, MD

  Boston Medical Center

  STUDY CHAIR

• David C. Seldin, MD, PhD

  Boston Medical Center

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 8, 2003
• First Posted: July 9, 2003
• Study Start: January 1, 2004
• Primary Completion: May 1, 2012
• Study Completion: November 1, 2015
• Last Updated: August 9, 2018
• Results First Posted: November 6, 2017

Record last verified: 2018-07

Locations

US (35)