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

Phase 1/2, Multi-center, Open Label, Dose Escalation, Safety, Efficacy and PK Study of PRLX 93936 Administered IV 3 Days a Week for 3 Weeks Followed by a 9 Day Rest Period in Patients With Relapsed or Relapsed/Refractory Multiple Myeloma

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).

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