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

This study has been withdrawn prior to enrollment.
(Temporarily closed to accrual pending availablity of drug.)
Sponsor:
Information provided by (Responsible Party):
University of Miami Sylvester Comprehensive Cancer Center
ClinicalTrials.gov Identifier:
NCT00504101
First received: July 17, 2007
Last updated: July 25, 2014
Last verified: August 2013
  Purpose

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

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: 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

Resource links provided by NLM:


Further study details as provided by University of Miami Sylvester Comprehensive Cancer Center:

Primary Outcome Measures:
  • Evaluate toxicity of the conditioning treatment regimen. [ Time Frame: 3 ¼ years ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Evaluate response and overall survival (OS). [ Time Frame: 3 ¼ years ] [ Designated as safety issue: No ]
  • Determine what correlative laboratory and clinical parameters, if any, are associated with efficacy [ Time Frame: 3 ¼ years ] [ Designated as safety issue: No ]

Enrollment: 0
Study Start Date: June 2007
Study Completion Date: June 2011
Primary Completion Date: June 2011 (Final data collection date for primary outcome measure)
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.
Detailed Description:

OBJECTIVES:

Primary

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

Secondary

  • 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.

  Eligibility

Ages Eligible for Study:   18 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

DISEASE CHARACTERISTICS:

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

PATIENT CHARACTERISTICS:

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)

PRIOR CONCURRENT THERAPY:

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
  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00504101

Locations
United States, Florida
University of Miami Sylvester Comprehensive Cancer Center - Miami
Miami, Florida, United States, 33136
Sponsors and Collaborators
University of Miami Sylvester Comprehensive Cancer Center
Investigators
Study Chair: Mark S. Goodman, MD University of Miami Sylvester Comprehensive Cancer Center
  More Information

No publications provided

Responsible Party: University of Miami Sylvester Comprehensive Cancer Center
ClinicalTrials.gov Identifier: NCT00504101     History of Changes
Other Study ID Numbers: UMIAMI-20070104, SCCC-2006071
Study First Received: July 17, 2007
Last Updated: July 25, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by University of Miami Sylvester Comprehensive Cancer Center:
stage I multiple myeloma
stage II multiple myeloma
stage III multiple myeloma

Additional relevant MeSH terms:
Multiple Myeloma
Neoplasms, Plasma Cell
Plasmacytoma
Blood Protein Disorders
Cardiovascular Diseases
Hematologic Diseases
Hemorrhagic Disorders
Hemostatic Disorders
Immune System Diseases
Immunoproliferative Disorders
Lymphoproliferative Disorders
Neoplasms
Neoplasms by Histologic Type
Paraproteinemias
Vascular Diseases
Arsenic trioxide
Bortezomib
Melphalan
Alkylating Agents
Antineoplastic Agents
Antineoplastic Agents, Alkylating
Immunologic Factors
Immunosuppressive Agents
Molecular Mechanisms of Pharmacological Action
Myeloablative Agonists
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses

ClinicalTrials.gov processed this record on November 25, 2014