Copanlisib and Gemcitabine in Relapsed/Refractory PTCL

Inclusion Criteria:

* Histologically confirmed relapsed or refractory PTCL or NK/T-cell lymphomas, excluding primary cutaneous T-cell lymphoma, and Sezary syndrome based on WHO classification,
* Age ≥ 19
* ECOG performance status ≤ 2
* at least one bi-dimensional measurable lesion
* Laboratory values

  * Serum Cr \< 1.5 mg/dL or CrCl \> 50 mL/min
  * Transaminase (AST/ALT) \< 2.5 x ULN (or \< 5 x ULN in the presence of lymphoma involvement of the liver)
  * Bilirubin \< 1.5 x UNL ( or \< 3 x ULN in the presence of lymphoma involvement of the liver or Gilbert syndrome)
  * PT (INR) ≤ 1.5 x ULN and aPTT ≤ 1.5 x ULN
  * Lipase ≤ 1.5 x ULN
  * Hematologic functions: absolute neutrophil count (ANC) ≥ 1,500/µL and platelet count ≥ 75,000/µL, hemoglobin ≥ 8 g/dL
* Left ventricular ejection fraction (LVEF) ≥ the lower limit of normal for the institution
* Women of childbearing potential and men must agree to use adequate contraception when sexually active
* Written informed consent

Exclusion Criteria:

* B-cell NHL, or primary cutaneous T-cell lymphoma and Sezary syndrome
* Patients who had previous history of lymphoma involvement of the CNS.
* History of previous gemcitabine therapy
* Type I or II diabetes mellitus with HbA1c \> 8.5% at screening
* History of chronic hepatitis B; subjects positive for HBsAg will be excluded from this study. However, subjects with HBcAb will be eligible if they are negative for HBV DNA quantification
* History of chronic hepatitis C; subjects positive for HCV IgG will be eligible if they are negative for HCV-RNA quantification
* Known history of human immunodeficiency virus (HIV) infection
* History or concurrent condition of interstitial lung disease of any severity and/or severely impaired lung function
* Any other malignancies within the past 3 years except curatively treated basal cell carcinoma of the skin, carcinoma in situ of the uterine cervix, or papillary carcinoma of the thyroid
* Other serious illness or medical conditions

  * Congestive heart failure \> NYHA class 2 (Appendix III)
  * Unstable angina or new-onset angina within the last 3 months; Myocardial infarction within 6 months prior to study entry
  * History of significant neurological or psychiatric disorders including dementia or seizure
  * Uncontrolled hypertension despite optimal medical management (per investigator's opinion)
  * Arterial or venous thrombotic or embolic events such as cerebrovascular accident (including transient ischemic attacks), deep vein thrombosis or pulmonary embolism within 6 months before start of study treatment
  * Non-healing wound, ulcer, or bone fracture
  * Active uncontrolled infection (viral, bacterial, or fungal infection)
  * Patients with evidence or history of bleeding diathesis. Any hemorrhage or bleeding event ≥ grade 3 within 4 weeks of start of study medication
  * Proteinuria estimated by urine protein/creatinine ratio \> 3.5 on a random urine sample
  * Concurrent diagnosis of pheochromocytoma
* Other previous or concurrent treatments

  * Ongoing immunosuppressive therapy
  * Radiotherapy or immune-/chemotherapy less than 4 weeks before start of treatment
  * Radioimmunotherapy or autologous transplant less than 3 months before start of treatment
  * Myeloid growth factors within 14 days prior to treatment start
  * Blood or platelet transfusion within 7 days prior to treatment start
  * Systemic continuous corticosteroid therapy at a daily dose higher than 15 mg prednisone or equivalent
  * History of having received an allogeneic bone marrow or organ transplant
  * Major surgical procedure or significant trauma injury within 28 days before start of study medication, open biopsy within 7 days before start of study treatment
  * Anti-arrhythmic therapy (beta-blockers or digoxin are permitted)
  * Use of CYP3A4 inhibitor or inducer
* Pregnant or lactating women, women of childbearing potential not employing adequate contraception
* Concomitant administration of any other experimental drugs under investigation