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Melphalan and Autologous Stem Cell Transplant Followed By Bortezomib and Dexamethasone in Treating Patients With Previously Untreated Systemic Amyloidosis

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Memorial Sloan-Kettering Cancer Center
ClinicalTrials.gov Identifier:
NCT00458822
First received: April 9, 2007
Last updated: September 19, 2012
Last verified: September 2012
History of Changes
  Purpose

RATIONALE: Giving chemotherapy, such as melphalan, before a peripheral stem cell transplant stops the growth of plasma cells by stopping them from dividing or killing them. Giving colony-stimulating factors, such as G-CSF, helps stem cells move from the bone marrow to the blood so they can be collected and stored. Chemotherapy 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. Bortezomib may stop the growth of plasma cells by blocking some of the enzymes needed for cell growth. Giving bortezomib and dexamethasone after transplant may kill any plasma cells that remain after transplant.

PURPOSE: This phase II trial is studying how well giving melphalan together with an autologous stem cell transplant followed by bortezomib and dexamethasone works in treating patients with previously untreated systemic amyloidosis.


Condition Intervention Phase
Multiple Myeloma and Plasma Cell Neoplasm
 Drug: bortezomib
Drug: dexamethasone
 Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Risk-Adapted Intravenous Melphalan With Stem Cell Transplant and Adjuvant Bortezomib and Dexamethasone for Recently Diagnosed Untreated Patients With Systemic Light-Chain (AL) Amyloidosis

Resource links provided by NLM:

U.S. FDA Resources

Further study details as provided by Memorial Sloan-Kettering Cancer Center:

Primary Outcome Measures:
  • Response rate at 12 months [ Time Frame: 12 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Toxicity [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
  • Amyloid disease response at 12 and 24 months [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  • Progression-free survival at 12 and 24 months [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  • Overall survival at 12 and 24 months [ Time Frame: 2 years ] [ Designated as safety issue: No ]

Estimated Enrollment: 45
Study Start Date: February 2007
Estimated Study Completion Date: February 2013
Estimated Primary Completion Date: February 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Group 1
Patients receive bortezomib IV on days 1, 4, 8, and 11 and oral dexamethasone once daily on days 1, 2, 4, 5, 8, 9, 11, and 12. Treatment repeats every 3 weeks for 2 courses. Patients then receive bortezomib on days 1, 8, 15, and 22 and dexamethasone on days 1, 2, 8, 9, 15, 16, 22, and 23. Treatment repeats every 5 weeks for up to 4 courses in the absence of disease progression or unacceptable toxicity. Patients who achieve complete response (CR) receive bortezomib and dexamethasone for 2 additional courses after CR.
 Drug: bortezomib
Given IV
Drug: dexamethasone
Given orally
Experimental: Group 2
Patients receive oral dexamethasone once daily on days 1-4, 9-12, and 17-20. Treatment repeats every 30 days for up to 10 courses in the absence of disease progression or unacceptable toxicity. Patients who achieve CR receive dexamethasone for 2 additional courses after CR.
 Drug: bortezomib
Given IV
Drug: dexamethasone
Given orally

Detailed Description:

OBJECTIVES:

Primary

  • Determine the response rate in patients with systemic light chain amyloidosis treated with melphalan and autologous stem cell transplantation followed by adjuvant bortezomib and dexamethasone.

Secondary

  • Determine the toxicity of this regimen in these patients.
  • Assess amyloid disease response to this regimen.
  • Determine the progression-free survival of patients treated with this regimen.
  • Determine the overall survival of patients treated with this regimen.

OUTLINE:

  • Stem cell mobilization and collection: Patients undergo peripheral blood stem cell (PBSC) mobilization comprising filgrastim (G-CSF) subcutaneously (SC) for 4-6 days. PBSC collection continues for 2-3 days until the target number of stem cells is reached.
  • Conditioning regimen: One week after PBSC collection, patients receive melphalan IV on days -3 and -2 and autologous PBSC infusion on day 0. Patients receive G-CSF SC beginning on day 1 and continuing until blood counts recover.

  • Adjuvant therapy: Between 2-3 months after PBSC transplantation, patients are assigned to 1 of 2 groups.

    • Group 1 (patients with plasma cell disease): Patients receive bortezomib IV on days 1, 4, 8, and 11 and oral dexamethasone once daily on days 1, 2, 4, 5, 8, 9, 11, and 12. Treatment repeats every 3 weeks for 2 courses. Patients then receive bortezomib on days 1, 8, 15, and 22 and dexamethasone on days 1, 2, 8, 9, 15, 16, 22, and 23. Treatment repeats every 5 weeks for up to 4 courses in the absence of disease progression or unacceptable toxicity. Patients who achieve complete response (CR) receive bortezomib and dexamethasone for 2 additional courses after CR.
    • Group 2 (patients with plasma cell disease and peripheral neuropathy): Patients receive oral dexamethasone once daily on days 1-4, 9-12, and 17-20. Treatment repeats every 30 days for up to 10 courses in the absence of disease progression or unacceptable toxicity. Patients who achieve CR receive dexamethasone for 2 additional courses after CR.

Patients undergo blood and bone marrow collection and tissue biopsies at baseline and periodically after completion of study treatment for biomarker correlative studies.

After completion of study treatment, patients are followed every 2 months for 2 year and then annually thereafter.

PROJECTED ACCRUAL: A total of 45 patients will be accrued for this study.

  Eligibility

Ages Eligible for Study:   18 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

DISEASE CHARACTERISTICS:

  • Histologically confirmed amyloidosis

    • Diagnosed within the past 12 months

    • Clonal plasma cell disorder, as demonstrated by any of the following:

      • Presence of M-protein in serum and/or urine by immunofixation and/or serum free light chain assay
      • Clonal population of plasma cells in the bone marrow based on kappa/lambda staining of a marrow biopsy
  • Negative genetic testing for hereditary forms of amyloidosis

  • No amyloid-specific syndrome (e.g., carpal tunnel syndrome or skin purpura) as the only evidence of disease

    • Vascular amyloidosis only in a bone marrow biopsy specimen or in plasmacytoma is not indicative of systemic amyloidosis
  • No advanced cardiac amyloidosis

  • Must have symptomatic involvement of no more than 2 of the following visceral organ systems:

    • Kidneys
    • Liver/gastrointestinal
    • Peripheral/autonomic nervous system
    • Heart
  • No persistent pleural effusions
  • No clinically overt multiple myeloma with > 30% plasma cells in the bone marrow or lytic bone lesions
  • Able to undergo autologous stem cell transplantation

PATIENT CHARACTERISTICS:

  • SWOG performance status 0-3
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception
  • Bilirubin < 2.0 mg/dL
  • Creatinine clearance < 51 mL/min allowed
  • LVEF > 45% by echocardiogram
  • No New York Heart Association class III-IV congestive heart failure
  • No history of cardiac syncope
  • No recurrent symptomatic arrhythmias
  • No oxygen-dependent restrictive cardiomyopathy
  • No myocardial infarction within the past 6 months
  • Pulmonary diffusion capacity > 50% predicted by pulmonary function testing
  • No uncontrolled infection

  • No other active malignancy, except for any of the following:

    • Adequately treated basal cell or squamous cell skin cancer
    • In situ cervical cancer
    • Adequately treated stage I cancer from which the patient is currently in complete remission
    • Any other cancer from which the patient has been disease-free for 5 years
  • No hypersensitivity to bortezomib, boron, or mannitol
  • No HIV positivity
  • No serious medical or psychiatric illness that would preclude study compliance

PRIOR CONCURRENT THERAPY:

  • At least 14 days since prior investigational drugs
  • No prior therapy for monoclonal plasma disease
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00458822

Locations
United States, New York
Memorial Sloan-Kettering Cancer Center
New York, New York, United States, 10065
Sponsors and Collaborators
Memorial Sloan-Kettering Cancer Center
National Cancer Institute (NCI)
Investigators
Principal Investigator: Heather Landau, MD Memorial Sloan-Kettering Cancer Center
  More Information

Additional Information:
Clinical trial summary from the National Cancer Institute's PDQ® database  This link exits the ClinicalTrials.gov site

No publications provided

Responsible Party: Memorial Sloan-Kettering Cancer Center
ClinicalTrials.gov Identifier: NCT00458822     History of Changes
Other Study ID Numbers: 07-006, MSKCC-07006
Study First Received: April 9, 2007
Last Updated: September 19, 2012
Health Authority: United States: Institutional Review Board

Keywords provided by Memorial Sloan-Kettering Cancer Center:
primary systemic amyloidosis

Additional relevant MeSH terms:
Amyloidosis
Neoplasms
Multiple Myeloma
Neoplasms, Plasma Cell
Plasmacytoma
Proteostasis Deficiencies
Metabolic Diseases
Neoplasms by Histologic Type
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Paraproteinemias
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
 Lymphoproliferative Disorders
Immunoproliferative Disorders
Immune System Diseases
Dexamethasone acetate
Dexamethasone
Dexamethasone 21-phosphate
Bortezomib
Melphalan
BB 1101
Anti-Inflammatory Agents
Therapeutic Uses
Pharmacologic Actions
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents

ClinicalTrials.gov processed this record on May 21, 2013