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

Memorial Sloan Kettering Cancer Center (MSK)

Status and phase: Completed; Phase 2

Conditions: Multiple Myeloma and Plasma Cell Neoplasm

Treatments: Drug: dexamethasone; Drug: bortezomib

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT00458822

07-006

MSKCC-07006

Details and patient eligibility

About

The purpose of this study in patients needing treatment for AL amyloidosis is to see how well treatment with IV melphalan works and then, if some clonal plasma cells are still present about 2 to 3 months after melphalan treatment, to see how well treatment with bortezomib and dexamethasone works to reduce the rest of the clonal plasma cell disease.

Enrollment: 40 patients

Sex: All

Ages: 18 to 70 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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40 participants in 1 patient group

All Patients

Experimental group

Description:

All patients treated with Melphalan with Stem Cell Transplant and Adjuvant Bortezomib and Dexamethasone for Recently Diagnosed Untreated Patients with Systemic Light-Chain (AL) Amyloidosis

Treatment:

Drug: dexamethasone

Drug: bortezomib