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

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Boston Medical Center
ClinicalTrials.gov Identifier:
NCT00790647
First received: November 12, 2008
Last updated: July 25, 2013
Last verified: July 2013
  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, such as G-CSF, 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 and Plasma Cell Neoplasm
Biological: filgrastim
Drug: bortezomib
Drug: melphalan
Procedure: autologous hematopoietic stem cell transplantation
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 Boston Medical Center:

Primary Outcome Measures:
  • Hematologic response (complete and partial) [ Time Frame: one year ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Tolerability [ Time Frame: 100 Days from transplant date ] [ Designated as safety issue: Yes ]
  • Survival at 1 and 2 years [ Time Frame: year one and two ] [ Designated as safety issue: No ]

Estimated Enrollment: 10
Study Start Date: June 2008
Estimated Study Completion Date: June 2015
Primary Completion Date: December 2012 (Final data collection date for primary outcome measure)
Intervention Details:
    Biological: filgrastim
    16 mcg/kg daily beginning 3 days before SCC through day before final SCC
    Other Name: G-CSF, 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: autologous hematopoietic stem cell transplantation
    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 (G-CSF) to mobilize stem cells, which are then collected.
  • Conditioning regimen: Patients receive bortezomib IV 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
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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 PCD by serum/urine or bone marrow; or overwhelmingly convincing clinical features (e.g., macroglossia) associated with other systemic manifestations
  • No senile, secondary, localized, dialysis-related, or familial amyloidosis
  • No overt multiple myeloma (> 30% of bone marrow plasmacytosis, extensive [> 2] lytic lesions, or hypercalcemia)

PATIENT CHARACTERISTICS:

  • SWOG performance status 0-1
  • Not pregnant or nursing
  • Fertile patients must use effective contraception
  • LVEF ≥ 45% by ECHO within the past 60 days
  • DLCO ≥ 50%
  • 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

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
  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

Additional Information:
No publications provided

Responsible Party: Boston Medical Center
ClinicalTrials.gov Identifier: NCT00790647     History of Changes
Other Study ID Numbers: CDR0000618857, BUMC-H-27277
Study First Received: November 12, 2008
Last Updated: July 25, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by Boston Medical Center:
primary systemic amyloidosis

Additional relevant MeSH terms:
Amyloidosis
Multiple Myeloma
Neoplasms, Plasma Cell
Plasmacytoma
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
Bortezomib
Melphalan
Alkylating Agents
Antineoplastic Agents
Antineoplastic Agents, Alkylating
Immunologic Factors
Immunosuppressive Agents
Molecular Mechanisms of Pharmacological Action
Myeloablative Agonists
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses

ClinicalTrials.gov processed this record on October 22, 2014