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)

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)

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

Study Overview

• Status: Completed
• Conditions: Non Hodgkin Lymphoma
• Intervention / Treatment: Drug: Tenalisib,

• Study Type: Interventional
• Enrollment (Actual): 20
• Phase: Phase 2

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Blacktown, New South Wales, Australia, 2148
      • Blacktown Hospital, Blacktown Cancer and Haematology Center
  • Queensland
    • Greenslopes,, Queensland, Australia, 4120
      • Brisbane Clinic for Lymphoma, Myeloma and Leukaemia,
    • Tugun, Queensland, Australia, 4224
      • John Flynn Private Hospital,
  • South Australia
    • Adelaide, South Australia, Australia, 5000
      • Royal Adelaide Hospital
• United States
  • Alabama
    • Huntsville, Alabama, United States, 35805
      • Clearview Cancer Institute
  • Colorado
    • Denver, Colorado, United States, 80218
      • Colorado Blood Cancer Institute
  • Florida
    • Florida City, Florida, United States, 33401
      • Florida Cancer Specialists & Research Institute
    • Fort Myers, Florida, United States, 33908
      • Florida Cancer Specialist/ South
    • Saint Petersburg, Florida, United States, 33705
      • Florida Cancer Specialists/North
  • Missouri
    • Kansas City, Missouri, United States, 64132
      • HCA Midwest Health Kansas City
  • Tennessee
    • Chattanooga, Tennessee, United States, 37404
      • Tennessee Oncology
    • Nashville, Tennessee, United States, 37203
      • Tennessee Oncology

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Rhizen Pharmaceuticals SA

Study record dates

Study Major Dates

• Study Start (Actual): November 25, 2018
• Primary Completion (Actual): June 16, 2020
• Study Completion (Actual): October 16, 2020

Study Registration Dates

• First Submitted: October 15, 2018
• First Submitted That Met QC Criteria: October 16, 2018
• First Posted (Actual): October 18, 2018

Study Record Updates

• Last Update Posted (Actual): August 12, 2021
• Last Update Submitted That Met QC Criteria: July 20, 2021
• Last Verified: July 1, 2021

More Information

Terms related to this study

• Keywords: Tenalisib; RP6530; Non-Hodgkin lymphoma,
• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Lymphoma; Lymphoma, Non-Hodgkin; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Phosphoinositide-3 Kinase Inhibitors; Tenalisib
• Other Study ID Numbers: RP6530-1802

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No