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


Phase 2
18 Years
70 Years
Open (Enrolling)
Both
Multiple Myeloma and Plasma Cell Neoplasm

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Trial Information

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


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.

Inclusion 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

Type of Study:

Interventional

Study Design:

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Response rate at 12 months

Outcome Time Frame:

12 months

Safety Issue:

No

Principal Investigator

Heather Landau, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

Memorial Sloan-Kettering Cancer Center

Authority:

United States: Institutional Review Board

Study ID:

07-006

NCT ID:

NCT00458822

Start Date:

February 2007

Completion Date:

February 2013

Related Keywords:

  • Multiple Myeloma and Plasma Cell Neoplasm
  • primary systemic amyloidosis
  • Amyloidosis
  • Neoplasms
  • Multiple Myeloma
  • Neoplasms, Plasma Cell
  • Plasmacytoma

Name

Location

Memorial Sloan-Kettering Cancer CenterNew York, New York  10021