Efficacy and Safety of Tenalisib (RP6530) in Patients With Relapsed/Refractory Chronic Lymphocytic Leukemia (CLL)

A Phase 2, Open Label Study to Assess the Efficacy and Safety of Tenalisib (RP6530), a Novel PI3K Dual δ/γ Inhibitor, in Patients With Relapsed/Refractory Chronic Lymphocytic Leukemia (CLL)

The trial is a Phase II, open label, Simon's two stage study design to evaluate the efficacy and safety of Tenalisib in patients with CLL who have relapsed or are refractory after at least one prior therapy.

Study Overview

• Status: Completed
• Conditions: Leukemia, Lymphocytic, Chronic, B-Cell
• Intervention / Treatment: Drug: Tenalisib

Detailed Description

Tenalisib is a highly specific and orally available dual PI3K δ/γ inhibitor. Pre-clinical experiments demonstrated that Tenalisib is highly effective in killing primary CLL cells in vitro. A Phase II study is planned to evaluate the efficacy and safety of Tenalisib in patients with relapsed/refractory CLL.

• Study Type: Interventional
• Enrollment (Actual): 21
• Phase: Phase 2

Contacts and Locations

Study Locations

• Bulgaria
  • Pleven, Bulgaria, 5800
    • University Multiprofile Hospital for Active Treatment "Dr Georgi Stranski" Ltd.,
  • Sofia, Bulgaria, 1431
    • University Multiprofile Hospital for Active Treatment "Sv Ivan Rilski" Ltd
• Georgia
  • Tbilisi, Georgia
    • Ltd. M.Zodelava Hematology Centre
  • Tbilisi, Georgia
    • Medivest - Institute of Hematology and Transfusiology
• Poland
  • Chorzow, Poland, 41-503
    • Silesian Healthy Blood Clinic Grosicki, Grosicka Sp.J.
  • Łódź, Poland
    • Voivodship Multi-Specialist Center for Oncology and Traumatology M. Copernicus

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 diagnosis of B-cell CLL
2. Disease status defined as refractory to or relapsed after at least one prior therapy.
3. Presence of measurable lymphadenopathy presence of > 1 nodal lesion
4. ECOG performance status ≤ 2.
5. Adequate bone marrow, liver, and renal function

Exclusion Criteria:

1. Richter's (large cell) transformation, or PLL transformation.
2. Cancer therapy/ any cancer investigational drug within 3 weeks (21 days) or 5 half-lives (whichever is shorter).
3. Prior exposure to drug that inhibits PI3K
4. Patient with ASCT/Allo-SCT receiving treatment for active GVHD.
5. Ongoing severe systemic bacterial, fungal or viral infection.
6. Central nervous system (CNS) involvement of leukemia or lymphoma.
7. Ongoing immunosuppressive therapy including systemic corticosteroids.
8. Known history of severe liver injury as judge by investigator.
9. Any severe and/or uncontrolled medical conditions or other conditions that could affect patient participation
10. Women who are pregnant or lactating.

11. Known seropositive requiring anti-viral therapy for i. human immunodeficiency virus (HIV) infection. ii. hepatitis B virus (HBV) infection iii. hepatitis c virus (HCV) infection iv. active CMV infection

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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; Patients receive Tenalisib 800 mg BID, Orally in 28-Day cycle for 7 cycles	Drug: Tenalisib; Tenalisib 800 mg BID, Orally; Other Names: RP6530

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Response Rate (ORR)	Per Response Evaluation Criteria as defined by iwCLL guideline for CLL: Complete Response (CR), all parameters should be regressed to normal (lymph nodes ≥ 1.5 cm; spleen size <13 cm; liver size normal; no constitutional symptoms; circulating lymphocyte count normal; platelet count ≥ 100 x 109 /L; Hemoglobin ≥ 11.0 g/dL). For partial response, at least two of the parameters (lymph nodes, liver and/or spleen size, constitutional symptoms, circulating lymphocyte count) and one parameter (platelet count, hemoglobin) need to improve if previously abnormal; Overall Response (OR) = CR + PR."	7 Months
Duration of Response (DoR)	Duration of response (DOR): DOR is defined as the interval from the first documentation of CR/PR to the first documentation of definitive disease progression or death from any cause. Progression disease is defined using iwCLL criteria as at least one of the criteria of parameters (i.e., lymph nodes increase ≥ 50% from baseline or from response; liver and/or spleen size increase ≥ 50% from baseline or from response; any constitutional symptoms; circulating lymphocyte count increase ≥ 50% over baseline) or criteria of parameters (i.e., platelet count decrease of ≥ 50% over baseline secondary to CLL; hemoglobin decrease of ≥ 50% over baseline secondary to CLL) should be met.	7 Months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Treatment-emergent Adverse Events as Assessed by CTCAE Criteria v5.0	Summary of Treatment-Emergent Adverse Events-(Causality All). Patients will be monitored for adverse events and both related and as well as non-related adverse events will be captured during the study. All adverse events (irrespective of causality) will be reported.	7 Months
Progression Free Survival (PFS)	Progression-free survival (PFS): PFS is defined as the interval from first dose to first documentation of definitive disease progression or death from any cause.	7 months

Collaborators and Investigators

• Sponsor: Rhizen Pharmaceuticals SA

Study record dates

Study Major Dates

• Study Start (Actual): November 28, 2019
• Primary Completion (Actual): October 2, 2020
• Study Completion (Actual): October 2, 2020

Study Registration Dates

• First Submitted: December 4, 2019
• First Submitted That Met QC Criteria: December 16, 2019
• First Posted (Actual): December 18, 2019

Study Record Updates

• Last Update Posted (Actual): July 23, 2021
• Last Update Submitted That Met QC Criteria: July 22, 2021
• Last Verified: July 1, 2021

More Information

Terms related to this study

• Keywords: Leukemia, Lymphocytic, Chronic, B-Cell; Tenalisib; Phosphoinositide 3-kinase; Pi3k Delta and gamma inhibitor
• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Leukemia, B-Cell; Leukemia; Leukemia, Lymphocytic, Chronic, B-Cell; Leukemia, Lymphoid; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Phosphoinositide-3 Kinase Inhibitors; Tenalisib
• Other Study ID Numbers: RP6530-1901

Drug and device information, study documents

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