Phase 1 Clinical Trial of NPI-0052 in Patients With Relapsed or Relapsed/Refractory Multiple Myeloma

• safety and toxicity profile [ Time Frame: Continuous ] [ Designated as safety issue: Yes ]
• pharmacokinetics [ Time Frame: Continuous ] [ Designated as safety issue: No ]
• biological activity [ Time Frame: Continuous ] [ Designated as safety issue: No ]
• Recommended Phase 2 Dose [ Time Frame: Continuous ] [ Designated as safety issue: No ]
• Response (EBMT criteria) [ Time Frame: Continuous ] [ Designated as safety issue: No ]

• safety and toxicity profile
• pharmacokinetics
• biological activity
• recommended phase 2 dose
• response (EBMT criteria)

This is a Phase 1 clinical trial examining the safety, pharmacokinetics and pharmacodynamics of escalating doses of the proteasome inhibitor NPI-0052 in patients with relapsed or relapsed/refractory multiple myeloma. By inhibiting proteasomes NPI-0052 prevents the breakdown of proteins involved in signal transduction, which blocks growth and survival in cancer cells.

Inclusion Criteria:

• Age >=18 years
• Karnofsky Performance Status (KPS) >=70%
• Histologic evidence of multiple myeloma, measurable relapsed or relapsed/refractory disease for which no other approved treatment is available and clinically indicated
• Adverse Events resulting from prior chemotherapy, surgery, or radiotherapy, must have resolved to acceptable grades
• Adequate bone marrow, renal, adrenal, pancreatic and liver function
• Hemoglobin >= 8 g/dL
• Absolute neutrophil count >= 0.5 x 10^9 /L
• Platelet count >= 30 x 10^9 /L (without transfusions)
• Signed informed consent
• Creatinine clearance >= 40 mL/min

Exclusion Criteria:

• Administration of chemotherapy, biological, immunotherapy or investigational agent within 14 days; 7 days for biologically targeted therapies and (6 weeks for nitrosourea and 12 weeks for BMT). Patients must be 2 weeks from radiation therapy.
• Patient's with > grade 1 proteinuria , untreated urinary tract infection, pre-existing kidney disease in the investigator's assessment would impose a risk to the patient
• Evidence of mucosal, internal bleeding and/or platelet refractory
• Significant cardiac disease
• Patients with a prior hypersensitivity reaction of CTCAE Grade >= 3 to therapy containing propylene glycol or ethanol.
• Pregnant or breast-feeding women
• Significant bacterial, viral or fungal infection
• Any other medical conditions that would impose excessive risk to the patient