Efficacy and Safety Study of Tenalisib (RP6530), a Novel PI3K δ/γ Dual Inhibitor in Patients With Relapsed/Refractory Indolent Non-Hodgkin's Lymphoma (iNHL)

Study Overview
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Brief Summary
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To assess the anti-tumor activity and safety of Tenalisib in patients with relapsed/refractory indolent Non-Hodgkin's Lymphoma (iNHL),

Official Title
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An Open Label, Phase II Study to Evaluate the Efficacy and Safety of Tenalisib (RP6530), a Novel PI3K δ/γ Dual Inhibitor in Adult Patients With Relapsed/Refractory Indolent Non-Hodgkin's Lymphoma (iNHL)

Conditions
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Non Hodgkin Lymphoma

Intervention / Treatment
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* Drug: Tenalisib,


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with histologically confirmed diagnosis of indolent B-cell NHL, with histological subtype limited to: Follicular lymphoma (FL) G1, G2, or G3a Marginal zone lymphoma (MZL) (splenic, nodal, or extra-nodal) Lymphoplasmacytic lymphoma/Waldenstrom macroglobulinemia (LPL/WM) Small lymphocytic lymphoma (SLL) with absolute lymphocyte count <5 x10^9/L at the time of diagnosis and at study entry. Relapsed or refractory after ≥ 2 prior lines of therapy (refractory defined as not responding to a standard regimen or progressing within 6 months of the last course of a standard regimen). Patients must have received rituximab and alkylating agents. Patients must have at least one bi-dimensionally measurable lesion (that has not been previously irradiated) with the longest diameter ≥ 1.5 cm. Male or female patients > 18 years of age. ECOG performance status ≤ 2. Life expectancy of at least 3 months. Adequate bone marrow, liver, and renal function as assessed by the following laboratory requirements conducted within 7 days before starting study treatment: Hemoglobin ≥ 9 g/dl Absolute neutrophil count (ANC) ≥ 1 x 10^9/L Platelets ≥50 x 10^9/L (patient without BM involvement) and 30 x 10^9/L (patient with BM involvement) Total bilirubin ≤1.5 times the upper limit of normal (ULN) Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤2.5 x ULN if known liver involvement Creatinine ≤ 1.5 mg/dL OR calculated creatinine clearance ≥ 50 mL/min (as calculated by the Cockcroft-Gault method) Use of an effective means of contraception for female patients of child-bearing potential, and all male partners. Willingness and ability to comply with trial and follow-up procedures, give written informed consent. Exclusion Criteria: FL grade 3b or transformed disease or CLL Cancer therapy within 3 weeks (21 days) or 5 half-lives (whichever is shorter) prior to C1D1. Corticosteroids (prednisone or equivalent) at a dose of < 20 mg daily are allowed. Corticosteroid should be stabilized for at least 1 week prior to C1D1 Auto-SCT within 3 months from C1D1 (patients must not have active graft versus- host disease) History of having received an Allo-SCT Active hepatitis B or C infection Known history of human immunodeficiency virus (HIV) infection Evidence of ongoing severe systemic bacterial, fungal or viral infection Known primary central nervous system lymphoma or any preexisting neurologic manifestations Known history of drug-induced liver injury, alcoholic liver disease, primary biliary cirrhosis, ongoing extrahepatic obstruction caused by stones, cirrhosis of the liver or portal hypertension; Prior exposure to drug that specifically inhibits PI3K Pregnancy or lactation Myeloid growth factors or red blood cells/ platelet transfusion within 14 days prior to C1D1 Drug administration within 1 week prior to C1D1 Strong inhibitors or inducers of CYP3A4, CYP2C9, including grapefruit products, herbal supplements and drugs Substrates of CYP3A4 enzyme with a narrow therapeutic range

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: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Tenalisib<br>Participants receive Tenalisib 800 mg BID in 28-Days Cycle for 8 Cycles | Drug: Tenalisib,<br>* BID, Orally<br>* Other names: RP6530;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective Response Rate (ORR) | ORR is defined as sum of CR and PR rates and will be assessed according to the Lugano Classification for initial evaluation, staging, and response assessment of Non-Hodgkin lymphoma. (Cheson-2014) | 7 months | 
| Complete Response Rate | CR rate will be assessed according to the Lugano Classification for initial evaluation, staging, and response assessment of non-Hodgkin lymphoma. | 7 months | 
| Progression Free Survival (PFS) | PFS is defined as the time of the first dose of Tenalisib to disease progression or death. | From date of first dose of tenalisib until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 7 months | 
| Duration of Response (DoR) | DoR is measured from the initial response to disease progression or death | 7 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Treatment-emergent Adverse Events as Assessed by CTCAE v4.0 | Safety and tolerability of Tenalisib | 8 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Non-Hodgkin lymphoma,, Tenalisib, RP6530