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Melphalan, Bortezomib, and Stem Cell Transplant in Treating Patients With Primary Systemic Amyloidosis

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Vaishali Sanchorawala, Boston Medical Center
ClinicalTrials.gov Identifier:
NCT00790647
First received: November 12, 2008
Last updated: December 13, 2016
Last verified: December 2016
  Purpose

RATIONALE: Giving melphalan and bortezomib before and after a stem cell transplant stops the growth of abnormal cells by stopping them from dividing or killing them. Giving colony-stimulating factors and certain chemotherapy drugs, helps stem cells move from the bone marrow to the blood so they can be collected and stored. Chemotherapy and monoclonal antibody therapy is then given to prepare the bone marrow for the stem cell transplant. The stem cells are then returned to the patient to replace the blood-forming cells that were destroyed by the chemotherapy.

PURPOSE: This phase II trial is studying how well giving melphalan together with bortezomib followed by stem cell transplant works in treating patients with primary systemic amyloidosis.


Condition Intervention Phase
Multiple Myeloma
Biological: filgrastim
Drug: bortezomib
Drug: melphalan
Procedure: Stem Cell Infusion
Phase 2

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase II Trial of High-dose Melphalan and Bortezomib and Stem Cell Transplantation in Patients With AL Amyloidosis

Resource links provided by NLM:


Further study details as provided by Vaishali Sanchorawala, Boston Medical Center:

Primary Outcome Measures:
  • Number of Participants With Hematologic Response [ Time Frame: one year ]

    complete and partial hematologic response defined as: Complete response: absence of detectable monoclonal protein in serum and urine, and bone marrow biopsy <5% plasma cells with no clonal predominance of kappa or lambda isotype.

    Partial response: any one of the following

    1. For patients with detectable and quantifiable marrow plasmacytosis, a reduction of 50% or more in plasma cells as a percentage of nucleated bone marrow cells.
    2. For patients with a detectable monoclonal peak on serum protein electropheresis or urine protein electropheresis, a reduction in the peak height of 50% or more.
    3. For patients with quantifiable urinary kappa or lambda chain concentration, a reduction in daily light chain excretion (concentration x 24-hr urine volume).


Secondary Outcome Measures:
  • Number of Participants Surviving at 100 Days From Transplant [ Time Frame: 100 Days from transplant date ]
  • Number of Participants Surviving at 1 Year [ Time Frame: one year from transplant ]
  • Number of Participants Surviving at 2 Years [ Time Frame: 2 years from transplant ]

Enrollment: 10
Study Start Date: June 2008
Study Completion Date: November 2014
Primary Completion Date: December 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Stem Cell Transplant with Bortezomib and Melphalan
Mobilization with Filgrastim Stem Cell Collection Bortezomib Melphalan Stem Cell infusion
Biological: filgrastim
16 mcg/kg daily beginning 3 days before stem cell collection through day before final stem cell collection
Other Name: Growth-Colony Stimulating Factor, neupogen
Drug: bortezomib
1.0 mg/m2/dose D -6, D-3, D +1, D + 4
Other Name: velcade
Drug: melphalan
100 mg/m2/dose D -2, D -1
Other Name: alkeran
Procedure: Stem Cell Infusion
infusion of previously collected autologous stem cells

Detailed Description:

OBJECTIVES:

  • To determine if hematologic responses to high-dose melphalan and autologous stem cell transplantation increase with addition of bortezomib in the conditioning regimen in patients with primary systemic amyloidosis.

OUTLINE:

  • Autologous stem cell mobilization and collection: Patients receive filgrastim to mobilize stem cells, which are then collected.
  • Conditioning regimen: Patients receive bortezomib intravenously on days -6, -3, 1, and 4 and oral high-dose melphalan on days -2 and -1.
  • Stem cell transplantation: Patients undergo autologous stem cell transplantation on day 0.

After completion of study therapy, patients are followed every 6 months for 1 year and annually thereafter.

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion criteria:

DISEASE CHARACTERISTICS:

  • Histologically confirmed primary systemic amyloidosis based on the following criteria:

    • Amyloid light-chain disease
    • Deposition of amyloid material by congo red stain showing characteristic green birefringence
    • Monoclonal light chain protein (Bence Jones protein) in the serum or urine, immunohistochemical studies, or serum free light chain assay
    • Evidence of tissue involvement other than carpal tunnel syndrome (i.e., positive immunohistochemical staining of bone marrow demonstrating clonal plasma cells); tissue amyloid deposits with anti-kappa or anti-lambda anti-serum; evidence for a plasma cell dyscrasia by serum/urine or bone marrow; or overwhelmingly convincing clinical features (e.g., macroglossia) associated with other systemic manifestations

PATIENT CHARACTERISTICS:

  • Southwest Oncology Group performance status 0-1
  • Fertile patients must use effective contraception
  • Left ventricular ejection fraction ≥ 45% by Echocardiogram within the past 60 days
  • diffusion capacity of lung for carbon monoxide ≥ 50%

PRIOR CONCURRENT THERAPY:

  • Prior chemotherapy with alkylating agent allowed provided there is no morphological or cytogenetic evidence of myelodysplastic syndromes
  • Prior total cumulative dose of oral melphalan < 300 mg
  • At least 4 weeks since prior cytotoxic therapy and fully recovered

Exclusion criteria:

  • No senile, secondary, localized, dialysis-related, or familial amyloidosis
  • No overt multiple myeloma (> 30% of bone marrow plasmacytosis, extensive [> 2] lytic lesions, or hypercalcemia)
  • Not pregnant or nursing
  • No myocardial infarction within the past 6 months, congestive heart failure, or arrhythmia refractory to therapy
  • No prior malignancy except for any of the following:

    • Adequately treated basal cell or squamous cell skin cancer
    • In situ cervical cancer
    • Adequately treated stage I or II cancer currently in complete remission
    • Any cancer from which the patient has been disease-free ≥ 5 years
  • No advanced (grade 3-4) pre-existing neuropathy
  • No HIV positivity
  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: NCT00790647

Locations
United States, Massachusetts
Boston University Cancer Research Center
Boston, Massachusetts, United States, 02118
Sponsors and Collaborators
Boston Medical Center
Investigators
Principal Investigator: Vaishali Sanchorawala, MD Boston Medical Center
  More Information

Responsible Party: Vaishali Sanchorawala, Principal Investigator, Boston Medical Center
ClinicalTrials.gov Identifier: NCT00790647     History of Changes
Other Study ID Numbers: CDR0000618857
BUMC-H-27277 ( Other Identifier: Boston University Medical Center IRB )
Study First Received: November 12, 2008
Results First Received: September 9, 2016
Last Updated: December 13, 2016
Individual Participant Data  
Plan to Share IPD: No

Keywords provided by Vaishali Sanchorawala, Boston Medical Center:
primary systemic amyloidosis

Additional relevant MeSH terms:
Multiple Myeloma
Amyloidosis
Neoplasms, Plasma Cell
Neoplasms by Histologic Type
Neoplasms
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Paraproteinemias
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Lymphoproliferative Disorders
Immunoproliferative Disorders
Immune System Diseases
Proteostasis Deficiencies
Metabolic Diseases
Bortezomib
Melphalan
Lenograstim
Antineoplastic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Myeloablative Agonists
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Adjuvants, Immunologic

ClinicalTrials.gov processed this record on May 25, 2017