Study of the efficacy and safety of copanlisib (BAY 80-6946) and gemcitabine combination in patients with relapsed/refractory peripheral T-cell or NK/T-cell lymphomas
- Conditions
- Neoplasms
- Registration Number
- KCT0003053
- Lead Sponsor
- Chonnam National University Hospital Hwasun Hospital
- Brief Summary
Copanrisib and gemcitabine combination therapy is a safe and effective treatment option for patients with relapsed/refractory peripheral T-cell lymphoma.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- All
- Target Recruitment
- 28
• Histologically confirmed relapsed or refractory PTCL or NK/T-cell lymphomas, excluding primary cutaneous T-cell lymphoma, and Sezary syndrome based o WHO classification
:relapsed or refractory disease are defined as disease relapse in patients achieved complete response from prior combination chemotherapy or partial response or less from prior combination chemotherapy
• Age = 19
• ECOG performance status = 2
• At least one bi-dimensional measurable lesion, which is defined as longest diameter of lymph node > 1.5cm or extranodal lesion > 1.0cm according to the Lugano classification
• Laboratory values
-Serum Cr < 1.5mg/dL or CrCl > 50mL/min
-Transminase(AST/ALT) <2.5 x upper normal value (or <5xULN in the pressence of the liver)
-Bilirubin <1.5 x upper normal value (or < 3 xULN 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/ul and platelet count = 75,000/ul, 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
-This applies since signing fo the informed consent form untill at least 3 months after the last study drug administration
-Adequate contraception is defined in the study as highly dffective birth control method (failure rate of less than 1%) e.g. intrauterine device(IUD), intrauterine hormone-releasing system(IUS), bilateral tubal occlusion, vasectomized partner, and sexual abstinence. The use of condoms by male patients is required unless the famale partne is permanently sterile
• Written informed consent
• B-cell NHL, or primary cutaneous T-cell lymphoma and Sezary syndrome
• Patients who had previous history of lymphoma involvement of the CNS. However, patients who have had only prophylactic chemotherapyp against CNS disease are eligible
• History ofo previous gemcitabine or PI3K inhibitor 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 hyman immynodeficiency virus(HIV) infection
• History or concurrent condition of intestitial lung disease of any severity and/or severely inpaired lung funcion
• Any other malignancies within the pase 3 years except curatively treated basal cell carcinoma of the skin, carcinoma in situ of the uterine cervis, or papillary carcinoma of the thyriod
• Other serious illness or medical conditions
-Congestive heart failure > NYHA class 2
-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, uncer, or bone fracture
-Actibe uncontrolled infection (viral, bacterial, or fungal infection)
-Patients with ebidence or history of bleeding diathesis. Any hemorrhage or bleening event = grage 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 th treatment start
-Blood or platelet transfusion within 7 days prior to treatment start
-Systemic continuous corticosteroid therapy at a daily dose higher than 15mg prednisone or equivalent
-History of having received an allogeneic bone marrow or organ trasplant
-Major surgical procedure or significant trauma injury within 28days before start of study medication, open biopsy within 7days 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 remploying adequate contraception
• Concomitant administration of any other experimental drugs under investigation
Study & Design
- Study Type
- Interventional Study
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method To determaine the maximum tolerated dose(MTD) of copanlisib;Objective response
- Secondary Outcome Measures
Name Time Method To evaluated the safety and tolerability