Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outcomes
Outline
Trial Contact Information
Registry Information

Alternate Title

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

Basic Trial Information

Phase	Type	Status	Age	Sponsor	Protocol IDs
Phase II	Treatment	Active	18 to 70	NCI	MSKCC-07006 07-006, NCT00458822

Objectives

Primary

1. 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

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

Entry 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

Prior/Concurrent Therapy:

• At least 14 days since prior investigational drugs
• No prior therapy for monoclonal plasma disease

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

Expected Enrollment

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

Outcomes

Response rate at 12 months

Toxicity
Amyloid disease response at 12 and 24 months
Progression-free survival at 12 and 24 months
Overall survival at 12 and 24 months

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 1 year and then annually thereafter.

Trial Contact Information

Trial Lead Organizations

Memorial Sloan-Kettering Cancer Center

Raymond Comenzo, MD, Principal investigator		Ph: 212-639-8086; 800-525-2225 Email: comenzor@mskcc.org
Hani Hassoun, MD, Principal investigator		Ph: 212-639-3228; 800-525-2225 Email: hassounh@mskcc.org
Adam Cohen, MD, Principal investigator		Ph: 212-639-5165; 800-525-2225

U.S.A.
New York
	New York
	Memorial Sloan-Kettering Cancer Center
		Raymond Comenzo, MD	Ph:  212-639-8086 800-525-2225
			Email: comenzor@mskcc.org

Registry Information
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
Trial Start Date		2007-02-13
Trial Completion Date		2010-02-15 (estimated)
Registered in ClinicalTrials.gov		NCT00458822
Date Submitted to PDQ		2007-02-21
Information Last Verified		2009-07-05
NCI Grant/Contract Number		CA08748

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