safety, efficacy and pharmacokinetic study of prlx 93936 in patients with multiple myeloma

Conditions: Multiple Myeloma

Summary: to determine the maximum tolerated dose of, and response to, prlx 93936 as treatment for patients with relapsed or relapsed/refractory multiple myeloma.

* to determine the maximum tolerated dose (mtd) and the dose limiting toxicities (dlt) of prlx 93936 administered iv 3 days a week (monday, wednesday and friday) for 3 weeks followed by a 9 day rest period, as treatment for patients with relapsed or relapsed/refractory multiple myeloma. * to establish the dose of prlx 93936 recommended for future studies. * to characterize potential toxicities of prlx 93936. * to assess the pharmacokinetic profile of prlx 93936. * to evaluate response to treatment, time to response (ttr) and duration of response. * to evaluate time to progression (ttp).

Eligibility criteria:
inclusion criteria: * patient must have a diagnosis of multiple myeloma and have relapsed or relapsed/refractory disease. * patient must have received ≥ 2 prior anti-myeloma regimens including a proteasome inhibitor and/or immunomodulatory agent. * patient currently requires systemic therapy. * patient has measurable disease. * age ≥ 18 years * karnofsky performance status ≥ 60% * ecog performance 0, 1 or 2 * life expectancy of at least three months * able to take acetaminophen * not pregnant * patient must have recovered from toxicities incurred as a result of any previous anti-myeloma therapy or recovered to baseline. * patients who received an autologous stem cell transplant must be ≥ 3 months post-transplant and all associated toxicities must have resolved to ≤ ctcae grade 1. * qt intervals of qtc ≤ 500 msec exclusion criteria: * poems syndrome * plasma cell leukemia * primary amyloidosis * patient has smoldering multiple myeloma or monoclonal gammopathy of unknown significance (mgus). * evidence of spinal cord compression or cns complication unless controlled by appropriate therapy. * patient received chemotherapy or other anti-cancer therapy that may be active against multiple myeloma within 3 weeks prior to the first dose of prlx 93936. * patient received nitrosureas within 6 weeks prior to the first dose. * patient received corticosteroids within 2 weeks prior to the first dose. * patient received plasmapheresis within 4 weeks prior to the first dose. * patient had major surgery within 4 weeks prior to the first dose. * patient had an allogeneic stem cell transplant within 6 months before first dose of prlx 93936 or has evidence of graft versus host disease. * patient is taking any therapy concomitantly that may be active against multiple myeloma. * patient is currently receiving medication(s) that are principally metabolized via the cytochrome p450 3a4 enzyme pathway. * use of any investigational agents within 28 days or 5 half-lives (whichever is shorter) of study treatment. * patient has peripheral neuropathy of grade 3 or greater intensity, or painful grade 2, as defined by the nci ctc. * patient had a myocardial infarction within 6 months of enrollment or has nyha class iii or iv heart failure uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities. * abnormal lvef (\< lln for the institution for a patient of that age) on echocardiogram * patient has poorly controlled hypertension, diabetes mellitus, or other serious medical or psychiatric illness that could potentially interfere with the completion of treatment according to protocol. * patient had a malignancy other than multiple myeloma within 3 years before enrollment, with the exception of adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, in situ breast cancer, or in situ prostate cancer. * patient's clinical laboratory values meet any of the following criteria within the 7 days prior to study day 1: * bilirubin \> 1.5 times uln * ast (sgot), alt (sgpt) and alkaline phosphatase \> 2.5 times uln * uncontrolled hypercalcemia (defined as serum calcium \> 14 mg/dl) * serum creatinine \> 2.0 mg/dl or creatinine clearance of \< 30 ml/min * anc \ 50% marrow involvement * platelet count \< 50,000 cells/mm3 * hemoglobin \< 8.0 g/dl * patient is known to be human immunodeficiency virus (hiv)-positive. * patient is known to be hepatitis b surface antigen-positive or has known active hepatitis c infection. * patient has an active systemic infection requiring treatment or within 14 days before first dose of prlx 93936. * pregnant or nursing women

Keywords: myeloma prlx93936