A Phase 1/2a Dose-Finding Study of PT-112 in Patients With Relapsed or Refractory Multiple Myeloma

Exclusion Criteria

• •1. Any of the following concomitant diseases/conditions:
• •* History or presence of myocardial infarction, clinically relevant valvular heart disease, or congestive heart failure within the last 12 months;
• •* Unstable cardiac dysrhythmias or persistent prolongation of the corrected QT interval (QTc) (Fridericia) to \>480 msec for males or \>500 msec for females, based on ECG at screening (patients with stable atrial fibrillation on treatment are allowed provided they do not meet any other cardiac or prohibited drug exclusion criterion);
• •* Presence of current angina;
• •* Active uncontrolled infection;
• •* Morphological or cytological features of myelodysplasia and/or post-chemotherapy aplasia on BM assessment;
• •* Myopathy \> grade 2 or any clinical situation that causes significant and persistent elevation of CPK (\>2.5 x ULN in two different determinations performed one week apart);
• •* Peripheral neuropathy \> grade 1, except for grade 2 without limitations on instrumental daily life activities;
• •* POEMS syndrome or active plasma cell leukemia;
• •* Chronic graft versus host disease (GVHD) or on immunosuppressive therapy for the control of GVHD;
• •* History or presence within the last 3 months of Deep Vein Thrombosis (DVT) or a pulmonary embolism (PE);- Uncontrolled leptomeningeal disease;
• •* Uncontrolled disease-related metabolic disorder (e.g., hypercalcemia);
• •* Acute or chronic infections requiring systemic therapy, including, among others:
• •* active infection requiring systemic therapy;
• •* history of testing positive to human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome;
• •* hepatitis B virus (HBV) or hepatitis C virus (HCV) infection at screening (positive HBV surface antigen or HCV RNA if anti-HCV antibody screening test is positive);
• •* active tuberculosis (history of exposure or history of positive TB test with presence of clinical symptoms, physical or radiographic finding);
• •* Any other major illness that, in the Investigator's judgment, may substantially increase the risk associated with the patient's participation in this study;
• •2. History of prior malignancy other than those previously treated with a curative intent more than 5 years ago and without relapse (any tumor) or basal cell skin cancer, in situ cervical cancer, superficial bladder cancer, or high grade intestinal polyps treated adequately, regardless of the disease-free interval;
• •3. Prior irradiation to \> 30% of BM reserves (including total body irradiation), regardless of the washout period;
• •4. High dose chemotherapy followed by autologous stem cell transplantation within 90 days prior to initiating study treatment;
• •5. Bisphosphonate treatment within 7 days prior to initiating study treatment (while on study, bisphosphonates can be administered only once a month, between Days 18 to 21 of the 28-day treatment cycle)