Safety, Efficacy and Pharmacokinetic Study of PRLX 93936 in Patients With Multiple Myeloma

Launched by PROLEXYS PHARMACEUTICALS · Sep 25, 2012

Keywords

ClinConnect Summary

* 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).

Gender

ALL

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 \< 1000 cells/mm3 or \< 750 cells/mm3 due to \>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