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

NCT00790647 | Completed Phase 2 Results DMC

• 2 other identifiers: CDR0000618857BUMC-H-27277
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

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.

Conditions

Multiple Myeloma

Keywords

primary systemic amyloidosis

Outcome Measures

Primary Outcomes (1)

• Number of Participants With Hematologic Response

  complete and partial hematologic response defined as: Complete response: absence of detectable monoclonal protein in serum and urine, and bone marrow biopsy \<5% plasma cells with no clonal predominance of kappa or lambda isotype. Partial response: any one of the following 1. For patients with detectable and quantifiable marrow plasmacytosis, a reduction of 50% or more in plasma cells as a percentage of nucleated bone marrow cells. 2. For patients with a detectable monoclonal peak on serum protein electropheresis or urine protein electropheresis, a reduction in the peak height of 50% or more. 3. For patients with quantifiable urinary kappa or lambda chain concentration, a reduction in daily light chain excretion (concentration x 24-hr urine volume).

  one year

Secondary Outcomes (3)

• Number of Participants Surviving at 100 Days From Transplant

  100 Days from transplant date

• Number of Participants Surviving at 1 Year

  one year from transplant

• Number of Participants Surviving at 2 Years

  2 years from transplant

Study Arms (1)

Stem Cell Transplant with Bortezomib and Melphalan

EXPERIMENTAL

Mobilization with Filgrastim Stem Cell Collection Bortezomib Melphalan Stem Cell infusion

Biological: filgrastim; Drug: bortezomib; Drug: melphalan; Procedure: Stem Cell Infusion

Interventions

filgrastim BIOLOGICAL

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

Also known as: Growth-Colony Stimulating Factor, neupogen

Stem Cell Transplant with Bortezomib and Melphalan

bortezomib DRUG

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

Also known as: velcade

Stem Cell Transplant with Bortezomib and Melphalan

melphalan DRUG

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

Also known as: alkeran

Stem Cell Transplant with Bortezomib and Melphalan

Stem Cell Infusion PROCEDURE

infusion of previously collected autologous stem cells

Stem Cell Transplant with Bortezomib and Melphalan

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Boston Medical Center: lead

Study Sites (1)

Boston University Cancer Research Center

Boston, Massachusetts, 02118, United States

Location

MeSH Terms

Conditions

Multiple Myeloma; Immunoglobulin Light-chain Amyloidosis

Interventions

Filgrastim; Bortezomib; Melphalan

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases; Amyloidosis; Proteostasis Deficiencies; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Granulocyte Colony-Stimulating Factor; Colony-Stimulating Factors; Glycoproteins; Glycoconjugates; Carbohydrates; Hematopoietic Cell Growth Factors; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors; Boronic Acids; Acids, Noncarboxylic; Acids; Inorganic Chemicals; Boron Compounds; Organic Chemicals; Pyrazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Phenylalanine; Amino Acids, Aromatic; Amino Acids, Cyclic; Amino Acids

Results Point of Contact

• Title: Vaishali Sanchorawala
• Organization: Boston Medical Center

vaishali.sanchorawala@bmc.org

617-638-8265

Study Officials

• Vaishali Sanchorawala, MD

  Boston Medical Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: November 12, 2008
• First Posted: November 13, 2008
• Study Start: June 1, 2008
• Primary Completion: December 1, 2012
• Study Completion: November 1, 2014
• Last Updated: February 6, 2017
• Results First Posted: February 6, 2017

Record last verified: 2016-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)