Efficacy Study of CYT997 in Multiple Myeloma

Inclusion Criteria:

• Diagnosis of multiple myeloma per International Working Group (IWG) criteria
• Have received at least 1 but no more than 4 prior lines of therapy
• Have failed to respond to the most recently administered anti-myeloma therapy
• Have a life expectancy of at least 3 months
• Eastern Cooperative Oncology Group (ECOG) performance status < 3
• At registration absolute neutrophil count > 1x10^9/L and platelet count > 50 x 10^9/L unsupported
• At registration bilirubin less than 1.5 x upper limit of normal and transaminases less than 2 x upper limit of normal and serum creatinine less than 0.19 mmol/L
• Written informed consent
• Must agree to adequate contraceptive measure if indicated

Exclusion Criteria:

• Patients with monoclonal gammopathy of undetermined significance
• Known or suspected hypersensitivity to CYT997
• Patient with uncontrolled intercurrent illness
• Active infections or other illnesses that precludes chemotherapy administration or patient compliance.
• Pregnant or lactating women.
• Patients who have received any other investigational agents in the last 3 weeks prior to the start of treatment.

• Patients with the following conditions will be excluded:

  • myocardial infarction or stroke within 6 months
  • unstable angina pectoris or acute ischemic changes on ECG
  • history of diabetic retinopathy
  • symptomatic peripheral arterial disease
  • major surgery in the last 30 days
• Patients with uncontrolled diarrhea despite optimal medication and those with any history of acute gastrointestinal bleeding
• Patients with a baseline prolongation of the QTc interval of Common Terminology Criteria (CTC) Grade 1 (QTc > 0.45-0.47 sec) or greater

• Patients with impaired cardiac function or clinically significant cardiac diseases, including any one of the following:

  • left ventricular ejection fraction (LVEF) < 45% as determined by multigated acquisition (MUGA) scan or echocardiogram;
  • complete left bundle branch block;
  • obligate use of a cardiac pacemaker;
  • congenital long QT syndrome;
  • history or presence of ventricular tachyarrhythmia;
  • presence of unstable atrial fibrillation (ventricular response > 100 bpm). -Patients with stable atrial fibrillation are eligible, provided they do not meet any of the other cardiac exclusion criteria;
  • clinically significant resting bradycardia (< 50 bpm);
  • right bundle branch block + left anterior hemiblock (bifascicular block);
  • angina pectoris ≤ 3 months prior to starting study drug;
  • acute myocardial infarction (MI) ≤ 3 months prior to starting study drug; or
  • other clinically significant heart disease (e.g., congestive heart failure (CHF), uncontrolled hypertension, history of labile hypertension, or history of poor compliance with an antihypertensive regimen).
• Patients currently receiving treatment with medications known to prolong the QTc interval and/or to induce Torsades de Pointes arrhythmia.