Multiple Myeloma and Plasma Cell Neoplasm
Conditions
Keywords
stage I multiple myeloma, stage II multiple myeloma, stage III multiple myeloma
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.
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.
Interventions
DRUGArsenic 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.
DRUGBortezomib
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.
DRUGMelphalan
Melphalan will be given at 200 mg/m2 on day -2 (1 dose only)
BIOLOGICALAutologous 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.
Sponsors
University of Miami
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
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%
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Evaluate toxicity of the conditioning treatment regimen. | 3 ¼ years |
Secondary
| Measure | Time frame |
|---|---|
| Evaluate response and overall survival (OS). | 3 ¼ years |
| Determine what correlative laboratory and clinical parameters, if any, are associated with efficacy | 3 ¼ years |
Countries
United States
Outcome results
None listed