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

Risk-Adapted Intravenous Melphalan With Stem Cell Transplant and Adjuvant Bortezomib and Dexamethasone for Recently Diagnosed Untreated Patients With Systemic Light-Chain (AL) Amyloidosis

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.

Study Overview

• Status: Completed
• Conditions: Multiple Myeloma and Plasma Cell Neoplasm
• Intervention / Treatment: Drug: dexamethasone; Drug: bortezomib

• Study Type: Interventional
• Enrollment (Actual): 40
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • New York
    • New York, New York, United States, 10065
      • Memorial Sloan Kettering Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: All Patients; 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	Drug: dexamethasone; Given orally; Drug: bortezomib; Given IV

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Hematologic and Organ Response	patients will be assessed for hematologic response (the response of the clonal plasma cell disease). If the plasma cell disease persists, then they will receive 6 cycles of adjuvant therapy with bortezomib and dexamethasone; patients with peripheral neuropathy will receive dexamethasone alone because of the risk of neuropathy associated with bortezomib. Symptomatic organ involvement with amyloid as defined below. Patients must have symptomatic involvement of no more than 2 of the following 4 visceral organ-systems: kidneys, liver/GI, peripheral/autonomic nervous system, and heart.	2-3 months post transplant

Collaborators and Investigators

• Sponsor: Memorial Sloan Kettering Cancer Center
• Collaborators: National Cancer Institute (NCI)

Study record dates

Study Major Dates

• Study Start: February 1, 2007
• Primary Completion (Actual): March 1, 2015
• Study Completion (Actual): March 1, 2015

Study Registration Dates

• First Submitted: April 9, 2007
• First Submitted That Met QC Criteria: April 9, 2007
• First Posted (Estimate): April 11, 2007

Study Record Updates

• Last Update Posted (Estimate): August 10, 2016
• Last Update Submitted That Met QC Criteria: June 29, 2016
• Last Verified: June 1, 2016

More Information

Terms related to this study

• Keywords: primary systemic amyloidosis
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Metabolic Diseases; Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Immunoproliferative Disorders; Hematologic Diseases; Hemorrhagic Disorders; Hemostatic Disorders; Paraproteinemias; Blood Protein Disorders; Proteostasis Deficiencies; Multiple Myeloma; Neoplasms, Plasma Cell; Amyloidosis; Plasmacytoma; Physiological Effects of Drugs; Autonomic Agents; Peripheral Nervous System Agents; Anti-Inflammatory Agents; Antineoplastic Agents; Antiemetics; Gastrointestinal Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Dexamethasone; Bortezomib
• Other Study ID Numbers: 07-006; MSKCC-07006