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Phase I Clinical Trial of Dose Escalated Bortezomib + ATO (Arsenic Trioxide) + Melphalan as a Conditioning Regimen for Multiple Myeloma

Phase 1
18 Years
70 Years
Not Enrolling
Multiple Myeloma and Plasma Cell Neoplasm

Thank you

Trial Information

Phase I Clinical Trial of Dose Escalated Bortezomib + ATO (Arsenic Trioxide) + Melphalan as a Conditioning Regimen for Multiple Myeloma



- 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.

Inclusion Criteria


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

- A minimum of 2 x 10^6 CD34+ cells/kg must be collected prior to proceeding to

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

- 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

Exclusion criteria:

- Previous autologous or allogeneic transplantation

- Other investigational or experimental drug or therapy while on the study

Type of Study:


Study Design:

Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Evaluate toxicity of the conditioning treatment regimen.

Outcome Time Frame:

3 ¼ years

Safety Issue:


Principal Investigator

Mark S. Goodman, MD

Investigator Role:

Study Chair

Investigator Affiliation:

University of Miami Sylvester Comprehensive Cancer Center


United States: Food and Drug Administration

Study ID:




Start Date:

June 2007

Completion Date:

June 2011

Related Keywords:

  • Multiple Myeloma and Plasma Cell Neoplasm
  • stage I multiple myeloma
  • stage II multiple myeloma
  • stage III multiple myeloma
  • Neoplasms
  • Multiple Myeloma
  • Neoplasms, Plasma Cell
  • Plasmacytoma



University of Miami Sylvester Comprehensive Cancer Center - MiamiMiami, Florida  33136