Safety and Efficacy of Tenalisib (RP6530) in Combination With Romidepsin in Patients With Relapsed/Refractory T-cell Lymphoma

Inclusion criteria

• Pathologically confirmed T-cell lymphomas at the enrolling institution.
• Disease status as defined as relapsed or progressed patients who have received at least one systemic therapy.
• The patients should have received NOT more than three prior systemic combination chemotherapies
• PTCL patients must have measurable disease defined as at least one bidimensional measurable lesion with minimum measurement of > 1.5 cm in the longest diameter.
• Must have ECOG performance status ≤ 2
• Adequate bone marrow, liver and renal function in line with below mentioned laboratory requirements.

• Hemoglobin ≥8.0 g/dL
• Absolute neutrophil count (ANC) ≥1,000/µL
• Platelet count ≥75,000/μL
• Total bilirubin ≤1.5 times the ULN (or ≤3 x ULN, if patient has Gilbert syndrome)
• AST (SGOT) and ALT (SGPT) ≤ 3 x ULN; ≤ 5 ULN in case of liver involvement
• Calculated creatinine clearance (CrCl) > 50 ml/min by Cockcroft-Gault formula
• Use of an effective means of contraception for women of childbearing potential and men with partners of childbearing potential.
• Provide written informed consent prior to any study-specific screening procedures.
• Willingness and capability to comply with the requirements of the study

Exclusion criteria

• Patient receiving anticancer therapy including any investigational therapy ≤3 weeks or 5 half-lives (whichever is shorter) prior to C1D1.
• Patient who discontinued prior therapy with PI3K inhibitors or HDAC inhibitors due to drug toxicity.
• PTCL patients with Allo-SCT on active GVHD or immunosuppression therapy within 3 months prior to C1D1. CTCL patients with the history of Allo-SCT will be excluded.
• Patient with medical conditions requiring the use of systemic immunosuppressive medications (> 20 mg/day of prednisone or equivalent).
• Severe bacterial, viral or mycotic infection requiring systemic treatment.
• Known seropositive requiring anti-viral therapy for human immunodeficiency virus (HIV) infection.
• Known seropositive requiring anti-viral therapy for hepatitis B virus (HBV) infection OR evidence of active hepatitis B infection as defined by detectable viral load if the antibody tests are positive..
• Known seropositive requiring anti-viral therapy for hepatitis c virus (HCV) infection OR patients with positive hepatitis C virus Ab.
• Subjects with active EBV unrelated to underlying lymphoma (positive serology for anti- EBV VCA IgM antibody and negative for anti-EBV EBNA IgG antibody, or clinical manifestations and positive EBV PCR consistent with active EBV infection.
• Subject with active CMV (positive serology for anti-CMV IgM antibody and negative for anti-CMV IgG antibody and positive CMV PCR with clinical manifestations consistent with active CMV infection) and requiring therapy.
• Uncontrolled or significant cardiovascular disease including, but not limited to:

• Congenital long QT syndrome.
• QTcF interval > 450 msec
• Myocardial infarction or stroke/TIA within the past 6 months
• Uncontrolled angina within the past 3 months
• Significant ECG abnormalities including 2nd degree atrio- ventricular (AV) block (AV) block type II, 3rd degree AV block.
• History of clinically significant arrhythmias (such as ventricular tachycardia, ventricular fibrillation or torsades de pointes),
• History of other clinically significant heart disease (ie, cardiomyopathy, congestive heart failure with NYHA functional classification III-IV, pericarditis, significant pericardial effusion)
• Requirement for daily supplemental oxygen therapy.