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Bortezomib, Arsenic Trioxide, and Melphalan in Treating Patients Undergoing an Autologous Stem Cell Transplant For Multiple Myeloma

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00504101
Recruitment Status : Withdrawn (Temporarily closed to accrual pending availablity of drug.)
First Posted : July 19, 2007
Last Update Posted : December 15, 2016
Information provided by (Responsible Party):
University of Miami

Brief Summary:

RATIONALE: Bortezomib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as arsenic trioxide and melphalan, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving high-dose combination chemotherapy together with bortezomib may kill more cancer cells.

PURPOSE: This phase I trial is studying the side effects and best dose of bortezomib when given together with arsenic trioxide and melphalan in treating patients undergoing an autologous stem cell transplant for multiple myeloma.

Condition or disease Intervention/treatment Phase
Multiple Myeloma and Plasma Cell Neoplasm Drug: Arsenic trioxide Drug: Bortezomib Drug: Melphalan Biological: Autologous hematopoietic stem cell transplantation Phase 1

Detailed Description:



  • Evaluate toxicity of a conditioning treatment regimen comprising bortezomib, arsenic trioxide, and melphalan.


  • Evaluate response and overall survival.
  • Determine what correlative laboratory and clinical parameters, if any, are associated with efficacy (e.g., serum arsenic trioxide intracellular glutathione depletion, gene profiling of myeloma cells).

OUTLINE: This is a dose-escalation study of bortezomib.

  • Conditioning regimen: Bortezomib will be given on days -6, -4, and -2, arsenic trioxide will be given on days -6, -5, -4, -3, and -2 (total of 5 doses), and melphalan will be given on day -2.
  • Stem cell infusion: On day 0 a minimum of autologous 2 x 10^6 CD34 cells/kg will be infused by central catheter.

After completion of study therapy, patients are followed periodically for at least 5 years.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 0 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase I Clinical Trial of Dose Escalated Bortezomib + ATO (Arsenic Trioxide) + Melphalan as a Conditioning Regimen for Multiple Myeloma
Study Start Date : June 2007
Actual Primary Completion Date : June 2011
Actual Study Completion Date : June 2011

Intervention Details:
  • Drug: Arsenic trioxide
    Arsenic Trioxide will be given on day -6, -5, -4,-3,-2 (total of 5 doses). The dose of Arsenic trioxide (ATO) is 0.25 mg/m2.
    Other Name: ATO (As2O3)
  • Drug: Bortezomib
    Bortezomib will be given on day -6, -4, -2 (total 3 doses) beginning at a dose of 0.8 mg/m2 each day of therapy.
    Other Names:
    • Velcade
    • PS-341
  • Drug: Melphalan
    Melphalan will be given at 200 mg/m2 on day -2 (1 dose only)
    Other Names:
    • L-PAM
    • L-phenylalanine mustard
    • L-sarcolysin
    • Alkeran
  • Biological: Autologous hematopoietic stem cell transplantation
    On day 0 a minimal of 2 x 106 CD 34 cells/kg will be infused by central catheter according to institutional standards.

Primary Outcome Measures :
  1. Evaluate toxicity of the conditioning treatment regimen. [ Time Frame: 3 ¼ years ]

Secondary Outcome Measures :
  1. Evaluate response and overall survival (OS). [ Time Frame: 3 ¼ years ]
  2. Determine what correlative laboratory and clinical parameters, if any, are associated with efficacy [ Time Frame: 3 ¼ years ]

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

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Ages Eligible for Study:   18 Years to 70 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No


Inclusion criteria:

  • Confirmed diagnosis of multiple myeloma (M-protein by serum protein electrophoresis or urine protein electrophoresis) and either bone marrow biopsy and aspirate demonstrating a plasma cell count > 10% or biopsy of a bone or soft tissue mass demonstrating a plasmacytoma

    • Demonstration of an indication for therapy based on symptoms (e.g., boney pain), hypercalcemia, anemia, renal insufficiency, symptomatic plasmacytomas, multiple boney lytic lesions, etc
    • Stable disease or has achieved a partial remission or complete remission to pre-transplant cyto-reductive therapy
    • Primary refractory disease (no response to therapy but stable) is permitted
  • Candidate for high-dose chemotherapy with autologous stem cell transplantation based on stabilization of disease with preparative chemotherapy (regardless of the specific agents)
  • A minimum of 2 x 10^6 CD34+ cells/kg must be collected prior to proceeding to transplant

Exclusion criteria:

  • Evidence of active plasma cell leukemia
  • Relapsed refractory disease (patients who have achieved at least a partial response [PR] to previous therapy and are now refractory [have not achieved a PR to subsequent therapy])
  • Progressive disease on their last therapy


Inclusion criteria:

  • Karnofsky performance status 60-100%
  • Creatinine < 3.0 mg/dL
  • AST and ALT <2.5 times upper limit of normal
  • Total bilirubin < 3 mg/dL
  • WBC ≥ 2,000/mm³
  • Platelet count ≥ 50,000/mm³
  • If abnormal hematologic function is attributable to bone marrow infiltration by multiple myeloma, the principal investigator will decide on a case-by-case basis if the patient's bone marrow reserve is appropriate for this study
  • Females of childbearing potential must have a negative serum pregnancy test prior to enrollment on the study and must use an effective barrier method while on the study
  • Ejection fraction > 40% and no history of uncontrolled ischemic heart disease or congestive heart failure
  • No evidence of cardiac amyloidosis by echocardiogram
  • DLCO and FEV_1 ≥ 50%

Exclusion criteria:

  • Active peripheral neuropathy ≥ grade 2
  • Recurrent supraventricular arrhythmia or any type of sustained ventricular arrhythmia or conduction block (e.g., A-V block grade II or III, left bundle branch block)
  • Known HIV infection
  • Pregnant or lactating women
  • Underlying medical condition that could be aggravated by the treatment or life-threatening disease unrelated to myeloma as evaluated by the enrolling physician
  • History of second malignancy within the past 3 years and not in complete remission from that malignancy, excluding adequately treated basal or squamous cell carcinoma of the skin, carcinoma in situ of the cervix, or local prostate cancer
  • History of preexisting neurological disorders (grade 2 or higher by the NCI Common Toxicity Criteria, in particular seizure disorders)


Inclusion criteria:

  • Previous radiation therapy for palliation of cord compression or pathologic fractures is permitted provided last dose is given 14 days prior to initiation of chemotherapy
  • Subjects with radiographic evidence of lytic bone disease receiving concomitant bisphosphonate therapy may be enrolled

    • Bisphosphonates should be held at least 1 week prior to the transplant but continuing bisphosphonates after day +60 is at the discretion of the treating physician

Exclusion criteria:

  • Previous autologous or allogeneic transplantation
  • Other investigational or experimental drug or therapy while on the study

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00504101

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United States, Florida
University of Miami Sylvester Comprehensive Cancer Center - Miami
Miami, Florida, United States, 33136
Sponsors and Collaborators
University of Miami
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Study Chair: Mark S. Goodman, MD University of Miami Sylvester Comprehensive Cancer Center
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Responsible Party: University of Miami Identifier: NCT00504101    
Other Study ID Numbers: 20070104
SCCC-2006071 ( Other Identifier: University of Miami Sylvester Comprehensive Cancer Center )
First Posted: July 19, 2007    Key Record Dates
Last Update Posted: December 15, 2016
Last Verified: December 2016
Keywords provided by University of Miami:
stage I multiple myeloma
stage II multiple myeloma
stage III multiple myeloma
Additional relevant MeSH terms:
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Multiple Myeloma
Neoplasms, Plasma Cell
Neoplasms by Histologic Type
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Lymphoproliferative Disorders
Immunoproliferative Disorders
Immune System Diseases
Arsenic Trioxide
Antineoplastic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Myeloablative Agonists
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs