VOB560-MIK665聯合治療用於血液惡性腫瘤患者（復發／難治性非何傑金氏淋巴瘤、復發／難治性急性髓系白血病或復發／難治性多發性骨髓瘤）的首次人體試驗

排除條件

• History of severe hypersensitivity reactions to any ingredient of study treatment and/or their excipients.
• Systemic antineoplastic therapy (including cytotoxic chemotherapy, alpha-interferon, kinase inhibitors or other targeted small molecules, and toxin immunoconjugates) or any experimental therapy within 14 days or 5 half-lives, whichever is shorter, before the first dose of study treatment.
• High-risk patients for Tumor Lysis Syndrome according to Cairo et al 2010 criteria or local guidelines.
• Impaired cardiac function or clinically significant cardiac disease, or history or current diagnosis of ECG abnormalities indicating significant risk of safety including any of the following:
• Concomitant clinically significant cardiac arrhythmias, e.g. sustained ventricular tachycardia, and clinically significant second- or third-degree AV block without a pacemaker
• Any history of clinical important abnormalities in rhythm, conduction or morphology of resting ECG e.g. complete left bundle branch block, third degree heart block
• Any factors that increase the risk of QTc prolongation or risk of arrhythmic events such as heart failure, significant hypokalemia, congenital long QT syndrome, family history of long QT syndrome or unexplained sudden death under 40 years of age
• Resting QTcF ≥450 msec (male) or ≥460 msec (female) at pre-treatment
• Use of agents known to prolong the QT interval unless it can be permanently discontinued for the duration of study.
• Abnormal echocardiogram (ECHO) or multi-gated acquisition scan (MUGA) at baseline (left ventricular ejection fraction \[LVEF\] \<50%)
• Symptomatic congestive heart failure (New York Heart Association ≥ 3)
• Findings observed in the baseline cardiac MRI that might reflect an increased risk for cardiac adverse events.
• Use of hematopoietic colony-stimulating growth factors (e.g. G-CSF, GM-CSF, M-CSF), thrombopoietin mimetics or erythroid stimulating agents ≤ 2 weeks prior to start of study treatment. If thrombopoietin mimetics or erythroid stimulating agents were initiated more than 2 weeks prior to the first dose of study treatment and the patient is on a stable dose, they can be maintained.
• For AML patients: Peripheral blast counts \> 25,000 blasts / mm3. Patients can receive hydroxyurea to control the peripheral blast counts as long as hydroxyurea can be stopped at least 24 hours prior to obtaining PD biomarkers at screening/baseline. Hydroxyurea can be restarted after sampling if clinically indicated to control blasts prior to the start of study treatment markers.
• For patients with R/R NHL and R/R MM:
• Absolute Neutrophil count \< 1.0 x 109/L
• Platelets count \< 50 x 109/ L
• Hemoglobin \< 8 g/dl
• Autologous stem cell transplant within 3 months before the first dose of study treatment.
• Patients who have undergone a prior allogeneic stem cell transplant before the first dose of study treatment.
• History of or current interstitial lung disease or pneumonitis grade ≥ 2.
• Impaired hepatic and renal function defined as:
• Serum aspartate aminotransferase (AST) or alanine aminotransferase (ALT) \> 1.5 x upper limit of normal (ULN)
• Bilirubin \>1.5 x ULN (unless bilirubin rise is due to Gilbert's syndrome or of non-hepatic origin)
• Creatinine clearance \<50 mL/min (calculated using Cockroft-Gault formula, or measured).
• Lipase \>1.5 x ULN or serum amylase \>1.5 x ULN and no history of pancreatitis.
• Increased cardiac troponin above the manufacturer's 99th percentile upper reference limit for local assay at screening