bb-10901 in treating patients with relapsed and/or refractory multiple myeloma

Conditions: Multiple Myeloma

Summary: rationale: monoclonal antibodies, such as bb-10901, can block cancer growth in different ways. some block the ability of cancer cells to grow and spread. others find cancer cells and help kill them or carry cancer-killing substances to them. purpose: this phase i trial is studying the side effects and best dose of bb-10901 in treating patients with relapsed and/or refractory multiple myeloma.

objectives: primary * determine the dose-limiting toxicity and the maximum tolerated dose of bb-10901 in patients with relapsed and/or refractory cd56-positive multiple myeloma. secondary * to determine the qualitative and quantitative toxicities of bb-10901 administered on this schedule. * to evaluate the pharmacokinetics of bb-10901. * to recommend a dose for phase ii clinical studies with bb-10901 given on this specific regimen. * to observe any evidence of anti-tumor activity with bb-10901. objectives of mtd expansion cohort * to evaluate response rate including overall response rate (orr) and complete response rate (crr), and duration of response (dor). * to further assess time to progression (ttp), progression free survival (pfs), and overall survival (os). outline: this is an open-label, non-randomized, dose-escalation, multicenter study. patients receive bb-10901 iv over 1-2 hours on days 1 and 8. courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. cohorts of 3-6 patients receive escalating doses of bb-10901 until the maximum tolerated dose (mtd) is determined. the mtd is defined as the dose preceding that at which 2 of 6 patients experience dose-limiting toxicity. up to 40 patients are treated at the mtd. after completion of study treatment, patients are followed for short term follow-up and long term (up to 3 years) survival status. projected accrual: a total of 80 patients will be accrued for this study.

Eligibility criteria:
disease characteristics: * histologically confirmed multiple myeloma * relapsed or relapsed/refractory disease * failed ≥ 1 prior therapy for multiple myeloma * once the mtd is defined, only patients who have received at least 1 but equal or less than 6 prior chemotherapy regimens will be enrolled at this dose level * cd56-positive disease confirmed by immunohistochemistry or flow cytometry patient characteristics: * ecog (zubrod) performance status 0-2 * life expectancy ≥ 12 weeks * platelet count ≥ 75,000/mm\^3 * absolute neutrophil count \> 1,000/mm\^3 * hemoglobin ≥ 8.5 g/dl * ast and alt ≤ 3 times upper limit of normal (uln) * bilirubin ≤ 1.5 times uln * amylase and lipase within normal limits * creatinine ≤ 2 mg/dl * left ventricular ejection fraction ≥ lower limit of normal on muga or echo * not pregnant or nursing * negative pregnancy test * fertile patients must use effective contraception * no peripheral neuropathy ≥ grade 3 or painful grade 2 neuropathy * no significant cardiac disease, including any of the following: * myocardial infarction within the past 6 months * unstable angina * uncontrolled congestive heart failure * uncontrolled hypertension (i.e., recurrent or persistent increases in systolic blood pressure ≥ 180 mm hg or diastolic blood pressure ≥ 110 mm hg) * uncontrolled cardiac arrhythmias * cardiac toxicity ≥ grade 3 after prior chemotherapy * no history of multiple sclerosis or other demyelinating disease * no hemorrhagic or ischemic stroke within the past 6 months * no eaton-lambert syndrome (para-neoplastic syndrome) * no cns injury with residual neurological deficit (other than peripheral neuropathy ≤ grade 2) * no other malignancy within the past 3 years except adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, in situ breast cancer, or in situ prostate cancer * no clinically relevant active infection, including active hepatitis b or c infection or hiv infection * no other condition or disease, including laboratory abnormalities, that, in the opinion of the investigator, may preclude study treatment * no known recent biochemical or clinical evidence of pancreatitis or extensive metastatic disease involving the pancreas prior concurrent therapy: * see disease characteristics * at least 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin c) * at least 4 weeks since prior radiotherapy * at least 4 weeks since prior major surgery (except placement of a vascular access device or tumor biopsies) * more than 4 weeks since prior investigational agents * at least 2 weeks since prior antineoplastic therapy with biological agents * no prior hypersensitivity to monoclonal antibody therapy * no other concurrent investigational agents * no concurrent corticosteroids (except as indicated for other medical conditions \[\< 10 mg prednisone or equivalent\]; as pre-medication for administration of certain medications or blood products \[≤ 100 mg hydrocortisone\]; or for treatment of infusion reactions) * concurrent topical steroids allowed * no other concurrent antineoplastic treatment (e.g., chemotherapy, radiotherapy, or biological agents) * concurrent bisphosphonates allowed provided patient began bisphosphonates before study entry and is maintained on a stable dose during study treatment

Keywords: stage i multiple myeloma stage ii multiple myeloma stage iii multiple myeloma