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