Clinical trial NCT00002556 (phase 3, status: completed)
Conditions: stage i multiple myeloma, stage ii multiple myeloma, stage iii multiple myeloma
ICD codes: C90.01, C90.02, C90.00, C90.01, C90.02, C90.00, C90.01, C90.02, C90.00
Drugs: vincristine sulfate, carmustine, melphalan, cyclophosphamide, prednisone
SMILES: CC[C@]1(O)C[C@@H]2CN(C1)CCC1=C(NC3=CC=CC=C13)[C@@](C2)(C(=O)OC)C1=C(OC)C=C2N(C=O)[C@@H]3[C@]4(CCN5CC=C[C@](CC)([C@@H]45)[C@@H](OC(C)=O)[C@]3(O)C(=O)OC)C2=C1, ClCCNC(=O)N(CCCl)N=O, N[C@@H](CC1=CC=C(C=C1)N(CCCl)CCCl)C(O)=O, ClCCN(CCCl)P1(=O)NCCCO1, [H][C@@]12CC=C(C3=CC=CN=C3)[C@@]1(C)CC[C@@]1([H])[C@@]2([H])CC=C2C[C@@H](O)CC[C@]12C
Eligibility criteria:

        Inclusion Criteria:

          -  Patients must have a diagnosis of multiple myeloma confirmed by the presence of:

               -  Bone marrow plasmacytosis with >= 10% plasma cells or sheets of plasma cells or
                  biopsy-proven plasmacytoma

               -  In addition, at least 1 of the following ancillary criteria must be documented:

                    -  M-protein in the serum

                    -  M-protein in the urine

                    -  Radiographic evidence of osteolytic lesions (generalized osteoporosis
                       qualifies only if the bone marrow aspirate contains >= 20% plasma cells)

          -  Patients must have measurable disease; the following will constitute measurable
             disease; tests used to document measurable disease must be done within two weeks prior
             to registration; a bone marrow biopsy performed =< 6 weeks prior to registration is
             acceptable; Note: If present, all of these parameters must be followed for response

          -  Serum M-protein >= 1.0 g/dL by serum protein electrophoresis

          -  Urine M-protein (light chain) excretion > 200 mg/24 hours by urine protein
             electrophoresis

          -  Measurable plasmacytoma(s) of soft tissue (must be biopsy proven)

          -  Bone marrow plasmacytosis >= 20%

          -  Patients must not have been previously treated with chemotherapy; prior treatment of
             hypercalcemia with corticosteroids, bisphosphonates, or other agents does not
             disqualify the patient

          -  Patients refuses entry or is ineligible for S9321; Note: S9321, "Standard Dose Versus
             Myeloablative Therapy for Previously Untreated Symptomatic Multiple Myeloma" has
             priority over E5A93; patients with previously untreated multiple myeloma should be
             entered on S9321; patients who are ineligible for or decline entry to S9321 should be
             entered on E5A93 and E3A93 if eligible

          -  Patients treated with local radiotherapy to > 15% of the bone marrow area are
             ineligible; patients who require concurrent radiotherapy should have entry to the
             protocol deferred until the radiotherapy is completed; if, in the physician's opinion,
             the delay in systemic therapy would itself pose undue risk, the patient may be entered
             and receive concurrent radiotherapy; in this situation, for the first VBMCP cycle,
             Melphalan, BCNU and Cyclophosphamide should be given at 75% of the dose

          -  Patients with Stages I, II, or III disease according to a modification of the clinical
             staging system by Durie and Salmon are eligible; staging should be based on values
             obtained at the time of diagnosis unless patient has had a more abnormal value prior
             to supportive treatment, transfusion, etc.; include only values obtained prior to
             initiation of protocol treatment

          -  Pretreatment x-rays must be done within 6 weeks of registration; copies of the bone
             x-ray reports are required and must be submitted with on-study forms

          -  Bone marrow slides must be submitted

          -  Absolute neutrophil count (ANC) >= 1,000/mm^3

          -  Platelet count >= 50,000/mm^3

          -  Creatinine =< 5.0 mg/dL (NOTE: Patients with creatinine 2.0-5.0 mg/dL may be admitted
             to this study but must receive altered doses and schedules of therapy)

          -  Patients requiring dialysis are not eligible

          -  Bilirubin =< 2.0 mg/dL

          -  Serum glutamic oxaloacetic transaminase (SGOT) =< 2.5 x upper limit of normal

          -  Alkaline phosphatase =< 2.5 x upper limit of normal

          -  No myocardial infarction within previous 6 months, no significant arrhythmia within
             the prior 3 months; if hypertension is present, it should be under control prior to
             study entry

          -  Patients with a history of congestive heart failure or myocardial infarction must have
             a normal myocardial ejection fraction as determined by echogram or multiple gate
             acquisition (MUGA) scan

          -  No patient with angina requiring nitrates or beta blockers, or with a history of
             thrombophlebitis or pulmonary emboli within the previous 6 months and currently
             requiring anticoagulants

          -  Patients with concurrent reversible conditions, e.g., infection, hyperuricemia, cord
             compression, hyperviscosity syndrome, central nervous system (CNS) complications, or
             renal disease may be entered into this study after appropriate therapy for these
             complications is initiated and the condition is controlled; therapy must be fully
             documented and dated on the on-study form; Note: Hypercalcemia patients may be entered
             directly on study and may receive corticosteroids, bisphosphonates, or other agents as
             needed for control of hypercalcemia; Note: Anemia patients may be entered directly on
             study and may receive erythropoietin (epoetin alfa: Procrit, Epogen, Aranesp, etc.) or
             other agents as needed for control of anemia

          -  No smoldering multiple myeloma, nonsecretory myeloma, localized plasmacytomas,
             monoclonal gammopathy of undetermined significance (MGUS), or primary systemic
             amyloidosis (AL)

          -  No patient with second malignancies except: those treated with surgery alone who are
             disease free > 5 years or patients whose only other malignancy is non-melanoma skin
             cancer or carcinoma in situ of the cervix

          -  Patients >= 70 years must have a performance status of 0-2, and be specifically
             evaluated by their physician to determine if they can tolerate either regimen; they
             should not enter the study if the physician feels that they would be unable to
             tolerate either regimen

          -  Female patients of childbearing potential must have a negative pregnancy test
             documented before entering this study; these patients must be provided adequate
             guidance about birth control measures; lactating women will be ineligible

          -  Pre-treatment baseline Eastern Cooperative Oncology Group (ECOG) Performance Status
             must be assessed

          -  Patients that are known to have acquired immune deficiency syndrome (AIDS) are
             excluded from this trial because the safety of the agents on this population has not
             been established

          -  Participation in E3A93 is mandatory for all patients in E5A93; patients must be
             registered separately to each protocol, first to E5A93, then to E3A93; NOTE: Study
             participants from South African institutions are exempt from mandatory registration to
             E3A93 due to costs and problems associated with international shipping

          -  Patients must give written informed consent