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)
Condition: Non Hodgkin Lymphoma
MeSH terms: Lymphoma; Lymphoma, Non-Hodgkin
Intervention: Tenalisib,
Intervention description: BID, Orally
Intervention MeSH terms: Tenalisib
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 20.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Non-Hodgkin lymphoma,; Tenalisib; RP6530

Summary:

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

Eligibility criteria:

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