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

Primary Purpose

Multiple Myeloma

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
filgrastim
bortezomib
melphalan
Stem Cell Infusion
Sponsored by
Boston Medical Center
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Multiple Myeloma focused on measuring primary systemic amyloidosis

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Boston University Cancer Research Center

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Stem Cell Transplant with Bortezomib and Melphalan

Arm Description

Mobilization with Filgrastim Stem Cell Collection Bortezomib Melphalan Stem Cell infusion

Outcomes

Primary Outcome Measures

Number of Participants With Hematologic Response
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 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. 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. 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
Number of Participants Surviving at 1 Year
Number of Participants Surviving at 2 Years

Full Information

First Posted
November 12, 2008
Last Updated
December 13, 2016
Sponsor
Boston Medical Center
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1. Study Identification

Unique Protocol Identification Number
NCT00790647
Brief Title
Melphalan, Bortezomib, and Stem Cell Transplant in Treating Patients With Primary Systemic Amyloidosis
Official Title
Phase II Trial of High-dose Melphalan and Bortezomib and Stem Cell Transplantation in Patients With AL Amyloidosis
Study Type
Interventional

2. Study Status

Record Verification Date
December 2016
Overall Recruitment Status
Completed
Study Start Date
June 2008 (undefined)
Primary Completion Date
December 2012 (Actual)
Study Completion Date
November 2014 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Boston Medical Center

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Multiple Myeloma
Keywords
primary systemic amyloidosis

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
10 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Stem Cell Transplant with Bortezomib and Melphalan
Arm Type
Experimental
Arm Description
Mobilization with Filgrastim Stem Cell Collection Bortezomib Melphalan Stem Cell infusion
Intervention Type
Biological
Intervention Name(s)
filgrastim
Other Intervention Name(s)
Growth-Colony Stimulating Factor, neupogen
Intervention Description
16 mcg/kg daily beginning 3 days before stem cell collection through day before final stem cell collection
Intervention Type
Drug
Intervention Name(s)
bortezomib
Other Intervention Name(s)
velcade
Intervention Description
1.0 mg/m2/dose D -6, D-3, D +1, D + 4
Intervention Type
Drug
Intervention Name(s)
melphalan
Other Intervention Name(s)
alkeran
Intervention Description
100 mg/m2/dose D -2, D -1
Intervention Type
Procedure
Intervention Name(s)
Stem Cell Infusion
Intervention Description
infusion of previously collected autologous stem cells
Primary Outcome Measure Information:
Title
Number of Participants With Hematologic Response
Description
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 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. 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. For patients with quantifiable urinary kappa or lambda chain concentration, a reduction in daily light chain excretion (concentration x 24-hr urine volume).
Time Frame
one year
Secondary Outcome Measure Information:
Title
Number of Participants Surviving at 100 Days From Transplant
Time Frame
100 Days from transplant date
Title
Number of Participants Surviving at 1 Year
Time Frame
one year from transplant
Title
Number of Participants Surviving at 2 Years
Time Frame
2 years from transplant

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Vaishali Sanchorawala, MD
Organizational Affiliation
Boston Medical Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
Boston University Cancer Research Center
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02118
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
No

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

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