Details

Details

Title A Multicenter Phase 2 Study of Single-agent Filanesib (ARRY-520) in Patients With Advanced Multiple Myeloma

IRB ARRY1A14

CC 14-1209

Hospital Main Campus

Phase Phase 2

Disease Multiple Myeloma

Drug ARRY-520

Description

Description

Primary Objectives
  • Estimate the ORR for patients with low Baseline AAG
Secondary ObjectivesIn patients with low Baseline AAG and in patients with high Baseline AAG:
  • Evaluate additional measures of efficacy
  • Assess the safety of filanesib treatment
  • Assess exposure to filanesib
  • Assess correlation between filanesib exposure and changes in QTc
Exploratory Objectives
  • Evaluate Baseline AAG and assess the effect of filanesib treatment on AAG levels
Inclusion Criteria

Inclusion Criteria

  1. Provide a personally signed and dated informed consent document prior to initiation of any study-related procedures that are not considered standard of care.
  2. Male or female ≥ 18 years of age at time of informed consent.
  3. Patients with confirmed multiple myeloma whose treatment history must include all of the following:
    • Received at least 2 prior lines of therapy (induction therapy and stem cell transplant +/- maintenance are to be considered a single line of therapy).
    • Received at least 2 cycles of a bortezomib-containing regimen and 2 cycles of a lenalidomide-containing regimen, unless intolerant to these agents (defined as requiring discontinuation due to toxicity).
    • Disease refractory to a carfilzomib-containing regimen and/or a pomalidomide-containing regimen. Refractory is defined as either failure to achieve an MR or better while on therapy, or development of PD while on therapy or within 60 days from last dose of therapy
  4. Measurable multiple myeloma disease, defined as meeting at least one of the following criteria within 14 days prior to enrollment:
    • A monoclonal Ig (M-protein) concentration on serum protein electrophoresis (SPEP) of ≥ 1.0 g/dL.
    • Measurable urinary light chain secretion by quantitative analysis using urine protein electrophoresis (UPEP) of ≥ 200 mg/24 hours.
    • Involved serum free light chain (FLC) level ≥ 10 mg/dL, provided the serum FLC ratio is abnormal.
  5. Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2 within 14 days prior to enrollment.
  6. Adequate hematology laboratory values within 14 days prior to enrollment:
    • Neutrophils ≥ 1.5 x 109/L without growth factor support (defined as no growth factor administration for at least 14 days prior to observation). If the bone marrow contains ≥ 50% plasma cells, a neutrophil count of ≥ 1.0 x 109/L is allowed.
    • Platelets ≥ 75 x 109/L without transfusion support. If the bone marrow contains ≥ 50% plasma cells, a platelet count of ≥ 50 x 109/L is allowed.
  7. Adequate hepatic and renal function laboratory values within 14 days prior to enrollment:
    • Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3 x the upper limit of normal (ULN).
    • Total bilirubin ≤ 1.5 mg/dL, unless attributed to a conjugation abnormality (e.g., Gilbert's syndrome).
    • Serum creatinine ≤ 2.5 mg/dL or a calculated (Cockcroft and Gault formula) or measured creatinine clearance of ≥ 30 mL/min.
  8. If patient is female and of childbearing potential, she must have a negative serum beta human chorionic gonadotropin (β-HCG) test within 14 days prior to enrollment and consent to ongoing pregnancy testing during the course of the study.
  9. Male patients must agree to use an effective method of contraception per institutional standard through 90 days after the last administration of filanesib and female patients of childbearing potential must agree to use an effective method of contraception per institutional standard through 30 days after the last administration of filanesib.
  10. Willingness and ability to comply with scheduled visits, treatment plan, laboratory tests and other study procedures.
Exclusion Criteria

Exclusion Criteria

  1. Prior treatment with filanesib (ARRY-520) or any other KSP inhibitor.
  2. Past or current plasma cell leukemia (> 2 x 109/L circulating plasma cells and plasma cells accounting for ≥ 20% by white blood cell [WBC] differential).
  3. Primary amyloidosis (amyloidosis associated with multiple myeloma is allowed).
  4. POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein and skin changes).
  5. Autologous or allogeneic stem cell or bone marrow transplant within 3 months prior to enrollment.
  6. Concomitant malignancies or previous malignancies (other than multiple myeloma) with less than a 2-year disease-free interval at the time of enrollment. Patients with adequately resected basal or squamous cell carcinoma of the skin, carcinoma in situ of the cervix or breast, or Stage 1 prostate cancer are eligible irrespective of the time of diagnosis.
  7. Use of an investigational agent that is not expected to be cleared by the time of enrollment or that has been demonstrated to have prolonged side effects. Patients must have recovered from all side effects to a Grade 0 or 1 (except alopecia and neuropathy).
  8. Monoclonal antibody treatment for multiple myeloma within 28 days prior to enrollment.
  9. Cytotoxic therapy within 21 days prior to enrollment.
  10. Proteasome inhibitor therapy within 14 days prior to enrollment.
  11. Immunomodulatory agent therapy within 7 days prior to enrollment.
  12. Radiotherapy within 21 days prior to enrollment. However, if the radiation portal covered ≤ 5% of the bone marrow reserve, the patient is eligible irrespective of the end date of radiotherapy.
  13. Corticosteroid doses > 10 mg/day of prednisone or equivalent within 14 days prior to enrollment.
  14. Contraindication to filgrastim or mannitol.
  15. Any major surgery where adequate wound healing has not occurred prior to enrollment.
  16. Medical, psychiatric or other conditions that may interfere with patient safety or compromise the patient's ability to understand the patient information, to give informed consent, to comply with the study protocol, or to complete the study.
  17. Any severe concurrent disease or condition (including severe graft-versus-host disease, requirement for dialysis, symptomatic congestive heart failure [New York Heart Association Class III or IV], unstable angina pectoris, cardiac arrhythmia) which, in the judgment of the Investigator, would make the patient inappropriate for study participation.
  18. Known human immunodeficiency virus (HIV) seropositivity.
  19. Active hepatitis B or hepatitis C infection.
  20. Acute active infection requiring treatment.
  21. Pregnant or breastfeeding women.