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)
21
Enrollment
6
Locations
1
Arm
10.2
Actual Duration (Months)
3.5
Patients Per Site
0.3
Patients Per Site Per Month

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 DiseaseIntervention/TreatmentPhase
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

ArmIntervention/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

    SiteCityStateCountryPostal Code
    1University Multiprofile Hospital for Active Treatment "Dr Georgi Stranski" Ltd.,PlevenBulgaria5800
    2University Multiprofile Hospital for Active Treatment "Sv Ivan Rilski" LtdSofiaBulgaria1431
    3Ltd. M.Zodelava Hematology CentreTbilisiGeorgia
    4Medivest - Institute of Hematology and TransfusiologyTbilisiGeorgia
    5Silesian Healthy Blood Clinic Grosicki, Grosicka Sp.J.ChorzowPoland41-503
    6Voivodship Multi-Specialist Center for Oncology and Traumatology M. CopernicusŁódźPoland

    Sponsors and Collaborators

    • Rhizen Pharmaceuticals SA

    Investigators

    None specified.

    Study Documents (Full-Text)

    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
    Additional relevant MeSH terms:

    Study Results

    Participant Flow

    Recruitment Details
    Pre-assignment Detail
    Arm/Group TitleTenalisib
    Arm/Group DescriptionPatients receive Tenalisib 800 mg BID, Orally in 28-Day cycle for 7 cycles Tenalisib: Tenalisib 800 mg BID, Orally
    Period Title: Overall Study
    STARTED21
    COMPLETED21
    NOT COMPLETED0

    Baseline Characteristics

    Arm/Group TitleTenalisib
    Arm/Group DescriptionPatients receive Tenalisib 800 mg BID, Orally in 28-Day cycle for 7 cycles Tenalisib: Tenalisib 800 mg BID, Orally
    Overall Participants21
    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
    TitleOverall Response Rate (ORR)
    DescriptionPer 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 Frame7 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 TitleTenalisib
    Arm/Group DescriptionPatients receive Tenalisib 800 mg BID, Orally in 28-Day cycle for 7 cycles Tenalisib: Tenalisib 800 mg BID, Orally
    Measure Participants21
    Number (95% Confidence Interval) [percentage of participants]
    33.3
    158.6%
    2. Primary Outcome
    TitleDuration of Response (DoR)
    DescriptionDuration 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 Frame7 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 TitleTenalisib
    Arm/Group DescriptionPatients receive Tenalisib 800 mg BID, Orally in 28-Day cycle for 7 cycles Tenalisib: Tenalisib 800 mg BID, Orally
    Measure Participants21
    Median (95% Confidence Interval) [days]
    143
    3. Secondary Outcome
    TitleNumber of Participants With Treatment-emergent Adverse Events as Assessed by CTCAE Criteria v5.0
    DescriptionSummary 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 Frame7 Months

    Outcome Measure Data

    Analysis Population Description
    Patients who received at least 1 dose of study medication
    Arm/Group TitleTenalisib
    Arm/Group DescriptionPatients receive Tenalisib 800 mg BID, Orally in 28-Day cycle for 7 cycles Tenalisib: Tenalisib 800 mg BID, Orally
    Measure Participants21
    Number [participants]
    15
    71.4%
    4. Secondary Outcome
    TitleProgression Free Survival (PFS)
    DescriptionProgression-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 Frame7 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 TitleTenalisib
    Arm/Group DescriptionPatients receive Tenalisib 800 mg BID, Orally in 28-Day cycle for 7 cycles Tenalisib: Tenalisib 800 mg BID, Orally
    Measure Participants21
    Median (Inter-Quartile Range) [days]
    205

    Adverse Events

    Time Frame7 months
    Adverse Event Reporting Description
    Arm/Group TitleTenalisib
    Arm/Group DescriptionPatients 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
    Total2/21 (9.5%)
    Serious Adverse Events
    Tenalisib
    Affected / at Risk (%)# Events
    Total3/21 (14.3%)
    Blood and lymphatic system disorders
    Anemia1/21 (4.8%) 1
    Infections and infestations
    Pneumonia2/21 (9.5%) 3
    Other (Not Including Serious) Adverse Events
    Tenalisib
    Affected / at Risk (%)# Events
    Total15/21 (71.4%)
    Blood and lymphatic system disorders
    Anemia6/21 (28.6%) 10
    Neutropenia5/21 (23.8%) 18
    Thrombocytopenia2/21 (9.5%) 3
    Gastrointestinal disorders
    Diarrhea2/21 (9.5%) 2
    Investigations
    Alanine aminotransferase increased4/21 (19%) 7
    Aspartate aminotransferase increased4/21 (19%) 6
    Blood alkaline phosphatase increased2/21 (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.

    Results Point of Contact

    Name/TitlePrajak Barde MD
    OrganizationRhizen Pharmaceuticals
    Phone+41325800175
    Emailpjb@rhizen.com
    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