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

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Southwest Oncology Group
ClinicalTrials.gov Identifier:
NCT00064337
First received: July 8, 2003
Last updated: January 15, 2014
Last verified: January 2014
  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
Plasma Cell Myeloma
Biological: filgrastim
Drug: cyclophosphamide
Drug: dexamethasone
Drug: melphalan
Drug: thalidomide
Procedure: peripheral blood stem cell transplantation
Phase 2

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
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)

Resource links provided by NLM:


Further study details as provided by Southwest Oncology Group:

Primary Outcome Measures:
  • Overall survival [ Time Frame: 5 years ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Hematologic response [ Time Frame: 5 years ] [ Designated as safety issue: No ]
  • Qualitative and quantitative toxicity [ Time Frame: 5 years ] [ Designated as safety issue: Yes ]
  • Prognostic significance of cytogenetic markers [ Time Frame: 5 years ] [ Designated as safety issue: No ]

Estimated Enrollment: 100
Study Start Date: January 2004
Estimated Study Completion Date: November 2015
Estimated Primary Completion Date: July 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment

MM Induction: dexamethasone 20mg/d PO Days 1-4, 9-12 and 17-20 every 35 days for 2 cyclesand 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

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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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

  Show 35 Study Locations
Sponsors and Collaborators
Southwest Oncology Group
Investigators
Study Chair: Vaishali Sanchorawala, MD Boston Medical Center
Study Chair: David C. Seldin, MD, PhD Boston Medical Center
  More Information

Additional Information:
No publications provided

Responsible Party: Southwest Oncology Group
ClinicalTrials.gov Identifier: NCT00064337     History of Changes
Other Study ID Numbers: CDR0000315382, S0115, U10CA032102
Study First Received: July 8, 2003
Last Updated: January 15, 2014
Health Authority: United States: Federal Government

Keywords provided by Southwest Oncology Group:
primary systemic amyloidosis
stage II multiple myeloma
stage III multiple myeloma

Additional relevant MeSH terms:
Amyloidosis
Multiple Myeloma
Neoplasms, Plasma Cell
Blood Protein Disorders
Cardiovascular Diseases
Hematologic Diseases
Hemorrhagic Disorders
Hemostatic Disorders
Immune System Diseases
Immunoproliferative Disorders
Lymphoproliferative Disorders
Metabolic Diseases
Neoplasms
Neoplasms by Histologic Type
Paraproteinemias
Proteostasis Deficiencies
Vascular Diseases
BB 1101
Cyclophosphamide
Dexamethasone
Dexamethasone 21-phosphate
Dexamethasone acetate
Melphalan
Thalidomide
Alkylating Agents
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Anti-Bacterial Agents
Anti-Infective Agents
Anti-Inflammatory Agents

ClinicalTrials.gov processed this record on November 20, 2014