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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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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)

Conditions
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Leukemia, Lymphocytic, Chronic, B-Cell

Intervention / Treatment
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* Drug: Tenalisib


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with diagnosis of B-cell CLL Disease status defined as refractory to or relapsed after at least one prior therapy. Presence of measurable lymphadenopathy presence of > 1 nodal lesion ECOG performance status ≤ 2. Adequate bone marrow, liver, and renal function Exclusion Criteria: Richter's (large cell) transformation, or PLL transformation. Cancer therapy/ any cancer investigational drug within 3 weeks (21 days) or 5 half-lives (whichever is shorter). Prior exposure to drug that inhibits PI3K Patient with ASCT/Allo-SCT receiving treatment for active GVHD. Ongoing severe systemic bacterial, fungal or viral infection. Central nervous system (CNS) involvement of leukemia or lymphoma. Ongoing immunosuppressive therapy including systemic corticosteroids. Known history of severe liver injury as judge by investigator. Any severe and/or uncontrolled medical conditions or other conditions that could affect patient participation Women who are pregnant or lactating. 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 -

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
Interventional Model Description: 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.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Tenalisib<br>Patients receive Tenalisib 800 mg BID, Orally in 28-Day cycle for 7 cycles | Drug: Tenalisib<br>* Tenalisib 800 mg BID, Orally<br>* Other names: RP6530;|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Phosphoinositide 3-kinase, Pi3k Delta and gamma inhibitor, Tenalisib, Leukemia, Lymphocytic, Chronic, B-Cell