Arsenic Trioxide and Ascorbic Acid Combined With Bortezomib, Thalidomide, and Dexamethasone in Treating Patients With Relapsed or Refractory Multiple Myeloma or Plasma Cell Leukemia
Multiple Myeloma and Plasma Cell Neoplasm
About this trial
This is an interventional treatment trial for Multiple Myeloma and Plasma Cell Neoplasm focused on measuring stage II multiple myeloma, stage III multiple myeloma, refractory multiple myeloma, stage I multiple myeloma
Eligibility Criteria
DISEASE CHARACTERISTICS: Histologically confirmed multiple myeloma (MM) or plasma cell leukemia meeting 1 of the following criteria: Relapsed or refractory disease after treatment with prior effective therapy Exhibited < a partial response to the last therapy Measurable disease, defined by 1 of the following: Serum M protein ≥ 1.0 g/dL Urine M-protein ≥ 500 mg/24 hours Plasmacytoma with bidimensional measurements on CT scan or MRI (each axis ≥ 1 cm) Previously treated with ≥ 1 induction chemotherapy regimen for MM No known CNS involvement by multiple myeloma PATIENT CHARACTERISTICS: Age 18 and over Performance status Zubrod or SWOG 0-2 OR Karnofsky 60-100% Life expectancy More than 12 weeks Hematopoietic WBC ≥ 1,500/mm^3 Absolute neutrophil count ≥ 1,000/mm^3 Platelet count ≥ 80,000/mm^3 Hemoglobin ≥ 8.5 g/dL No history of heparin-induced thrombocytopenia Low blood counts allowed if marrow is heavily infiltrated by multiple myeloma Hepatic Bilirubin ≤ 1.5 times upper limit normal (ULN) AST and ALT ≤ 2.5 times ULN Renal Creatinine ≤ 2.5 mg/dL Cardiovascular QTc < 480 msec on EKG in the presence of serum potassium ≥ 4.0 mEq/dL and serum magnesium ≥ 1.8 mg/dL LVEF ≥ 55% by ECHO or MUGA No prior deep vein thrombosis, unless on concurrent anticoagulation No symptomatic congestive heart failure No unstable angina pectoris No history of ventricular arrhythmia Other Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception during and for 6 months after completion of study treatment No history of allergic reactions or severe adverse reactions attributed to compounds of similar chemical or biological composition to study drugs No other malignancy in the past 2 years except adequately treated nonmelanoma skin cancer or carcinoma in situ of the cervix No peripheral neuropathy ≥ grade 2 No ongoing or active infection requiring IV antibiotics No psychiatric illness or social situation that would preclude study compliance No other uncontrolled illness Controlled HIV disease allowed as long as there are no associated comorbid complications No active peptic ulcer disease No other condition that would confer a high risk of bleeding complications PRIOR CONCURRENT THERAPY: Biologic therapy More than 4 weeks since prior thalidomide or lenalidomide for MM Prior autologous or allogeneic stem cell transplant for MM allowed Concurrent hematopoietic growth factors (e.g., epoetin alfa, filgrastim [G-CSF]) for MM allowed Chemotherapy See Disease Characteristics More than 4 weeks since prior arsenic trioxide for MM Endocrine therapy More than 4 weeks since prior corticosteroids for MM Radiotherapy More than 4 weeks since prior therapeutic radiotherapy (e.g., to plasmacytomas) Palliative radiotherapy for painful symptomatic lytic skeletal lesions allowed within the past 4 weeks Surgery Not specified Other More than 4 weeks since prior cytotoxic agents or other therapy (e.g., bortezomib) for MM More than 30 days (or 5 half-lives) since prior investigational agents Concurrent bisphosphonates for MM allowed No other concurrent anticancer therapy No other concurrent investigational agents
Sites / Locations
- Barbara Ann Karmanos Cancer Institute
Arms of the Study
Arm 1
Experimental
Bortezomib, AT, Thalidomide, Dexamethasone, Vit C, ASA
Bortezomib (Velcade)- 0.7→1.0 mg/m2 IVP d 1, 4, 8, 11; Arsenic Trioxide [AT] (Trisenox)- 0.10→0.15→0.25 mg/kg/dose IVPB days 1, 4, 8, 11; Thalidomide (Thalomid)- 50 mg/day by mouth (PO); Dexamethasone (Decadron)- 40 mg/d IVPB or by mouth (PO) d 1, 4, 8, 11; Ascorbic Acid (Vit C)- 1000 mg IVPB p Arsenic Trioxide (ATO) days 1, 4, 8, 11; Aspirin (ASA)- 325 mg by mouth (PO) every day