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

• Sponsor: Rhizen Pharmaceuticals SA (Industry)
• Overall Status: Completed
• CT.gov ID: NCT04204057
• Collaborator: (none)
• Enrollment: 21
• Locations: 6
• Arm: 1
• Actual Duration (Months): 10.2
• Patients Per Site: 3.5
• Patients Per Site Per Month: 0.3

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Leukemia, Lymphocytic, Chronic, B-Cell	Drug: Tenalisib	Phase 2

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 Design

• Study Type: Interventional
• Actual Enrollment: 21 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Intervention 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.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)
• Masking Description: None (open label)
• Primary Purpose: Treatment
• Official Title: 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)
• Actual Study Start Date: Nov 28, 2019
• Actual Primary Completion Date: Oct 2, 2020
• Actual Study Completion Date: Oct 2, 2020

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

1. 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."

2. 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

1. 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.

2. 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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

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

Sponsors and Collaborators

• Rhizen Pharmaceuticals SA

Investigators

None specified.

Study Documents (Full-Text)

• Study Protocol - Sep 12, 2019
• Statistical Analysis Plan - Dec 14, 2020

More Information

Publications

None provided.

• Responsible Party: Rhizen Pharmaceuticals SA
• ClinicalTrials.gov Identifier: NCT04204057
• Other Study ID Numbers: RP6530-1901
• First Posted: Dec 18, 2019
• Last Update Posted: Jul 23, 2021
• Last Verified: Jul 1, 2021

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Rhizen Pharmaceuticals SA: Phosphoinositide 3-kinase; Pi3k Delta and gamma inhibitor; Tenalisib; Leukemia, Lymphocytic, Chronic, B-Cell
• Additional relevant MeSH terms: Leukemia; Leukemia, Lymphoid; Leukemia, Lymphocytic, Chronic, B-Cell; Tenalisib

Study Results

Participant Flow

Arm/Group Title	Tenalisib
Arm/Group Description	Patients receive Tenalisib 800 mg BID, Orally in 28-Day cycle for 7 cycles Tenalisib: Tenalisib 800 mg BID, Orally
Period Title: Overall Study
STARTED	21
COMPLETED	21
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	Tenalisib
Arm/Group Description	Patients receive Tenalisib 800 mg BID, Orally in 28-Day cycle for 7 cycles Tenalisib: Tenalisib 800 mg BID, Orally
Overall Participants	21
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	10 47.6%
>=65 years	11 52.4%
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	66.08
Sex: Female, Male (Count of Participants)
Female	3 14.3%
Male	18 85.7%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	0 0%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	0 0%
White	21 100%
More than one race	0 0%
Unknown or Not Reported	0 0%
Region of Enrollment (participants) [Number]
Poland	9 42.9%
Georgia	9 42.9%
Bulgaria	3 14.3%

Outcome Measures

1. Primary Outcome

Title	Overall Response Rate (ORR)
Description	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."
Time Frame	7 Months

Outcome Measure Data

Analysis Population Description

Patients who received at least 1 dose of study medication and provided at least 1 post-baseline efficacy assessment

Arm/Group Title	Tenalisib
Arm/Group Description	Patients receive Tenalisib 800 mg BID, Orally in 28-Day cycle for 7 cycles Tenalisib: Tenalisib 800 mg BID, Orally
Measure Participants	21
Number (95% Confidence Interval) [percentage of participants]	33.3 158.6%

2. Primary Outcome

Title	Duration of Response (DoR)
Description	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.
Time Frame	7 Months

Outcome Measure Data

Analysis Population Description

Patients who received at least 1 dose of study medication and provide at least post-baseline efficacy assessment

Arm/Group Title	Tenalisib
Arm/Group Description	Patients receive Tenalisib 800 mg BID, Orally in 28-Day cycle for 7 cycles Tenalisib: Tenalisib 800 mg BID, Orally
Measure Participants	21
Median (95% Confidence Interval) [days]	143

3. Secondary Outcome

Title	Number of Participants With Treatment-emergent Adverse Events as Assessed by CTCAE Criteria v5.0
Description	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.
Time Frame	7 Months

Outcome Measure Data

Analysis Population Description

Patients who received at least 1 dose of study medication

Arm/Group Title	Tenalisib
Arm/Group Description	Patients receive Tenalisib 800 mg BID, Orally in 28-Day cycle for 7 cycles Tenalisib: Tenalisib 800 mg BID, Orally
Measure Participants	21
Number [participants]	15 71.4%

4. Secondary Outcome

Title	Progression Free Survival (PFS)
Description	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.
Time Frame	7 months

Outcome Measure Data

Analysis Population Description

Patients who received at least 1 dose of study medication and provide at least 1 post-baseline efficacy assessment

Arm/Group Title	Tenalisib
Arm/Group Description	Patients receive Tenalisib 800 mg BID, Orally in 28-Day cycle for 7 cycles Tenalisib: Tenalisib 800 mg BID, Orally
Measure Participants	21
Median (Inter-Quartile Range) [days]	205

Adverse Events

Time Frame	7 months
Arm/Group Title	Tenalisib
Arm/Group Description	Patients receive Tenalisib 800 mg BID, Orally in 28-Day cycle for 7 cycles Tenalisib: Tenalisib 800 mg BID, Orally
All Cause Mortality
	Tenalisib
	Affected / at Risk (%)	# Events
Total	2/21 (9.5%)
Serious Adverse Events
	Tenalisib
	Affected / at Risk (%)	# Events
Total	3/21 (14.3%)
Blood and lymphatic system disorders
Anemia	1/21 (4.8%)	1
Infections and infestations
Pneumonia	2/21 (9.5%)	3
Other (Not Including Serious) Adverse Events
	Tenalisib
	Affected / at Risk (%)	# Events
Total	15/21 (71.4%)
Blood and lymphatic system disorders
Anemia	6/21 (28.6%)	10
Neutropenia	5/21 (23.8%)	18
Thrombocytopenia	2/21 (9.5%)	3
Gastrointestinal disorders
Diarrhea	2/21 (9.5%)	2
Investigations
Alanine aminotransferase increased	4/21 (19%)	7
Aspartate aminotransferase increased	4/21 (19%)	6
Blood alkaline phosphatase increased	2/21 (9.5%)	3

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.