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

Study Overview
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Brief Summary
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To characterize safety, tolerability and to establish the maximum tolerated dose (MTD) of Tenalisib in combination with Romidepsin in patients with R/R T-cell lymphoma.

Official Title
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An Open Label, Phase I/II Study to Evaluate the Safety and Efficacy of Tenalisib (RP6530), a Novel PI3K δ/γ Dual Inhibitor Given in Combination With a Histone Deacetylase (HDAC) Inhibitor, Romidepsin in Adult Patients With Relapsed/Refractory T-cell Lymphoma

Conditions
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T Cell Lymphoma

Intervention / Treatment
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* Drug: Tenalisib
* Drug: Romidepsin


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Tenalisib+Romidepsin<br>Participants receive Tenalisib in escalating doses daily Orally BID and Romidepsin in escalating doses intravenously on day 1, 8 and 15 | Drug: Tenalisib<br>* Tenalisib, BID orally daily<br>* Other names: RP6530;Drug: Romidepsin<br>* Romidepsin IV<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With and Without Dose Limiting Toxicities (DLTs) | The DLTs will be classified according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 5.0. | 28 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Response Rate (ORR) With Tenalisib and Romidepsin Combination | Overall response (ORR) = CR + PR) was assessed according to the Lugano classification with PTCL and according to the modified Severity Weighted Assessment Tool (mSWAT)/Global assessment in patients with CTCL. | 12 weeks | 
| Duration of Response (DoR) With Tenalisib and Romidepsin Combination | The time period from the response achieved in patient until the disease progression | 28 weeks | 
| Maximum Observed Plasma Concentration (Cmax) | Assessment of Cmax in subjects treated with Tenalisib and Romidepsin combination. Blood samples for measurement of RP6530 plasma concentrations were collected pre-dose and at 0.5, 1, 2, 3, 4, 6, 8, 10, and 11 hours after dosing on Day 8 of the first cycle. Maximum (peak) drug concentration (Cmax in nanograms/milliliter) was estimated using Single-Dose data. | 8 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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T cell Lymphoma, RP6530, Tenalisib, Romidepsin