Melphalan, Bortezomib, and Stem Cell Transplant in Treating Patients With Primary Systemic Amyloidosis

NCT ID: NCT00790647

Last Updated: 2017-02-06

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 10 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2008-06-30
• Study Completion Date: 2014-11-30

Brief Summary

RATIONALE: Giving melphalan and bortezomib before and after a stem cell transplant stops the growth of abnormal cells by stopping them from dividing or killing them. Giving colony-stimulating factors and certain chemotherapy drugs, helps stem cells move from the bone marrow to the blood so they can be collected and stored. Chemotherapy and monoclonal antibody therapy 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.

PURPOSE: This phase II trial is studying how well giving melphalan together with bortezomib followed by stem cell transplant works in treating patients with primary systemic amyloidosis.

Detailed Description

OBJECTIVES:

• To determine if hematologic responses to high-dose melphalan and autologous stem cell transplantation increase with addition of bortezomib in the conditioning regimen in patients with primary systemic amyloidosis.

OUTLINE:

• Autologous stem cell mobilization and collection: Patients receive filgrastim to mobilize stem cells, which are then collected.
• Conditioning regimen: Patients receive bortezomib intravenously on days -6, -3, 1, and 4 and oral high-dose melphalan on days -2 and -1.
• Stem cell transplantation: Patients undergo autologous stem cell transplantation on day 0.

After completion of study therapy, patients are followed every 6 months for 1 year and annually thereafter.

Conditions

Multiple Myeloma

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Stem Cell Transplant with Bortezomib and Melphalan

Mobilization with Filgrastim Stem Cell Collection Bortezomib Melphalan Stem Cell infusion

Group Type: EXPERIMENTAL

filgrastim

Intervention Type: BIOLOGICAL

16 mcg/kg daily beginning 3 days before stem cell collection through day before final stem cell collection

bortezomib

Intervention Type: DRUG

1.0 mg/m2/dose D -6, D-3, D +1, D + 4

melphalan

Intervention Type: DRUG

100 mg/m2/dose D -2, D -1

Stem Cell Infusion

Intervention Type: PROCEDURE

infusion of previously collected autologous stem cells

Interventions

filgrastim

16 mcg/kg daily beginning 3 days before stem cell collection through day before final stem cell collection

Intervention Type: BIOLOGICAL

bortezomib

1.0 mg/m2/dose D -6, D-3, D +1, D + 4

Intervention Type: DRUG

melphalan

100 mg/m2/dose D -2, D -1

Intervention Type: DRUG

Stem Cell Infusion

infusion of previously collected autologous stem cells

Intervention Type: PROCEDURE

Other Intervention Names

Growth-Colony Stimulating Factor, neupogen; velcade; alkeran

Eligibility Criteria

Inclusion Criteria

DISEASE CHARACTERISTICS:

• Histologically confirmed primary systemic amyloidosis based on the following criteria:

• Amyloid light-chain disease
• Deposition of amyloid material by congo red stain showing characteristic green birefringence
• Monoclonal light chain protein (Bence Jones protein) in the serum or urine, immunohistochemical studies, or serum free light chain assay
• Evidence of tissue involvement other than carpal tunnel syndrome (i.e., positive immunohistochemical staining of bone marrow demonstrating clonal plasma cells); tissue amyloid deposits with anti-kappa or anti-lambda anti-serum; evidence for a plasma cell dyscrasia by serum/urine or bone marrow; or overwhelmingly convincing clinical features (e.g., macroglossia) associated with other systemic manifestations

PATIENT CHARACTERISTICS:

• Southwest Oncology Group performance status 0-1
• Fertile patients must use effective contraception
• Left ventricular ejection fraction ≥ 45% by Echocardiogram within the past 60 days
• diffusion capacity of lung for carbon monoxide ≥ 50%

PRIOR CONCURRENT THERAPY:

• Prior chemotherapy with alkylating agent allowed provided there is no morphological or cytogenetic evidence of myelodysplastic syndromes
• Prior total cumulative dose of oral melphalan < 300 mg
• At least 4 weeks since prior cytotoxic therapy and fully recovered

Exclusion Criteria

• No senile, secondary, localized, dialysis-related, or familial amyloidosis
• No overt multiple myeloma (> 30% of bone marrow plasmacytosis, extensive [> 2] lytic lesions, or hypercalcemia)
• Not pregnant or nursing
• No myocardial infarction within the past 6 months, congestive heart failure, or arrhythmia refractory to therapy
• No prior malignancy except for any of the following:

• Adequately treated basal cell or squamous cell skin cancer
• In situ cervical cancer
• Adequately treated stage I or II cancer currently in complete remission
• Any cancer from which the patient has been disease-free ≥ 5 years
• No advanced (grade 3-4) pre-existing neuropathy
• No HIV positivity

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Boston Medical Center

OTHER

Sponsor Role: lead

Responsible Party

Vaishali Sanchorawala

Principal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Vaishali Sanchorawala, MD

Role: PRINCIPAL_INVESTIGATOR

Boston Medical Center

Locations

Boston University Cancer Research Center

Boston, Massachusetts, United States

Countries

United States

Other Identifiers

BUMC-H-27277

Identifier Type: OTHER

Identifier Source: secondary_id

CDR0000618857

Identifier Type: -

Identifier Source: org_study_id