Phase 2 Clinical Trial of NPI-0052 in Patients With Relapsed or Relapsed/Refractory Multiple Myeloma

Inclusion Criteria: Prior to Amendment 13:

• Age 18 years.
• Karnofsky Performance Status (KPS) score 70%.
• All patients must have histologic evidence of multiple myeloma. Evidence of relapsed or relapsed/refractory disease for which no other approved treatment is available and clinically indicated. In addition, patients may have undergone prior bone marrow transplantation. For patients treated at the Recommended Phase 2 Dose patients are required to have measurable relapsed or relapsed/refractory disease. Disease must be assessed within 28 days prior to treatment initiation.
• Measurable disease is defined as one of the following:
• Serum M-protein ≥0.5 g/dL
• Urine M-protein ≥200 mg/24 hours
• Involved serum free light chain (FLC) level ≥10 mg/dL, provided the serum FLC ratio is abnormal
• Relapsed and Refractory are defined as:
• Must have received at least 2 prior treatment regimens.
• Must have received prior treatment with at least 2 cycles of lenalidomide and at least 2 cycles of bortezomib (either in separate regimens or within the same regimen).
• Must have received a cytotoxic chemotherapy agent (eg, alkylating agent).
• Relapsed Disease: Must have progressive disease after having achieved at least stable disease for at least one cycle of treatment during at least one prior regimen.
• Refractory Disease: Must have documented evidence of progressive disease during or within 60 days (measured from the end of the last cycle) of completing the most recently received anti-myeloma drug regimen prior to study entry
• All AEs resulting from prior chemotherapy, surgery, or radiotherapy must have resolved to NCI-CTCAE Grade 1 (except for hematologic parameters outlined below).
• The following laboratory results, within 7 days prior to NPI-0052 administration (transfusions and/or growth factor support may be used with discretion by the Investigator during Screening):
• Hemoglobin 8 g/dL
• Absolute neutrophil count 0.5 × 109/L
• Platelet count 30 × 109/L
• Serum bilirubin 1.5 × ULN
• AST 2.5 × ULN
• Serum creatinine 1.5 × ULN
• Creatinine clearance ≥40 mL/min
• Signed informed consent.
• Must have previously received at least 2 cycles of carfilzomib (as a single agent or in combination with other agents) and subsequently had disease progression during or within 60 days of carfilzomib therapy. Carfilzomib does not have to be the most recent therapy that the patient has received, but patients must have documented disease progression during or within 60 days of their last anti-myeloma therapy

Inclusion Criteria Amendment 13:

• Age 18 years.
• Karnofsky Performance Status score 70%.
• All patients must have histologic evidence of multiple myeloma and evidence of relapsed or relapsed/refractory disease as defined below Patients are required to have measurable relapsed or relapsed/refractory disease. Disease must be assessed within 28 days prior to treatment initiation.
• Measurable disease defined as one of the following:
• Serum M-protein ≥0.5 g/dL
• Urine M-protein ≥200 mg/24 hours
• Involved serum free light chain (FLC) level ≥10 mg/dL provided the serum FLC ratio is abnormal
• Relapsed and Refractory are defined as:
• Must have received at least 2 prior treatment regimens.
• Must have received prior treatment with at least 2 cycles of an immunomodulator (lenalidomide or pomalidomide or thalidomide).
• Must have previously received at least 2 cycles of carfilzomib (as a single agent or in combination with other agents) and subsequently had disease progression during or within 60 days of carfilzomib therapy. Carfilzomib does not have to be the most recent therapy that the patient has received, but patients must have documented disease progression during or within 60 days of their last anti-myeloma therapy. Patients may also have received bortezomib.

In addition, patients may have undergone prior cytotoxic chemotherapy, bone marrow transplantation and previously participated in other clinical trials.

• Relapsed Dise