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

Phase 2

Completed

• Conditions: Leukemia, Lymphocytic, Chronic, B-Cell
• Interventions: Drug: Tenalisib

• Registration Number: NCT04204057
• Lead Sponsor: Rhizen Pharmaceuticals SA

Brief Summary

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

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 Timeline

• Study Start: 2019-11-28
• Study First Submitted: 2019-12-04
• Study First Submitted QC: 2019-12-16
• Study First Posted: 2019-12-18
• Primary Completion: 2020-10-02
• Study Completion: 2020-10-02
• Results First Submitted: 2021-07-02
• Results First Submitted QC: 2021-07-02
• Results First Posted: 2021-07-22
• Status Verified: 2024-08
• Last Update Submitted: 2024-08-10
• Last Update Posted: 2024-08-13

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 21

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Tenalisib	Tenalisib	Patients receive Tenalisib 800 mg BID, Orally in 28-Day cycle for 7 cycles

Primary Outcome Measures

Name	Time	Method
Overall Response Rate (ORR)	7 Months	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."
Duration of Response (DoR)	7 Months	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.

Secondary Outcome Measures

Name	Time	Method
Number of Participants With Treatment-emergent Adverse Events as Assessed by CTCAE Criteria v5.0	7 Months	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.
Progression Free Survival (PFS)	7 months	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.

Trial Locations

Locations (6)

Silesian Healthy Blood Clinic Grosicki, Grosicka Sp.J.; 🇵🇱 Chorzow, Poland

University Multiprofile Hospital for Active Treatment "Sv Ivan Rilski" Ltd; 🇧🇬 Sofia, Bulgaria

University Multiprofile Hospital for Active Treatment "Dr Georgi Stranski" Ltd.,; 🇧🇬 Pleven, Bulgaria

Ltd. M.Zodelava Hematology Centre; 🇬🇪 Tbilisi, Georgia

Medivest - Institute of Hematology and Transfusiology; 🇬🇪 Tbilisi, Georgia

Voivodship Multi-Specialist Center for Oncology and Traumatology M. Copernicus; 🇵🇱 Łódź, Poland