Leukemia, Lymphocytic, Chronic, B-Cell
Conditions
Keywords
Phosphoinositide 3-kinase, Pi3k Delta and gamma inhibitor, Tenalisib, Leukemia, Lymphocytic, Chronic, B-Cell
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.
Interventions
DRUGTenalisib
Tenalisib 800 mg BID, Orally
Sponsors
Rhizen Pharmaceuticals SA
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Masking description
None (open label)
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.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
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 \-
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
Countries
Bulgaria, Georgia, Poland
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Tenalisib Patients receive Tenalisib 800 mg BID, Orally in 28-Day cycle for 7 cycles
Tenalisib: Tenalisib 800 mg BID, Orally | 21 |
| Total | 21 |
Baseline characteristics
| Characteristic | Tenalisib |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 11 Participants |
| Age, Categorical Between 18 and 65 years | 10 Participants |
| Age, Continuous | 66.08 years |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 21 Participants |
| Region of Enrollment Bulgaria | 3 participants |
| Region of Enrollment Georgia | 9 participants |
| Region of Enrollment Poland | 9 participants |
| Sex: Female, Male Female | 3 Participants |
| Sex: Female, Male Male | 18 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 2 / 21 |
| other Total, other adverse events | 15 / 21 |
| serious Total, serious adverse events | 3 / 21 |
Outcome results
Primary
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.
Time frame: 7 Months
Population: Patients who received at least 1 dose of study medication and provide at least post-baseline efficacy assessment
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Tenalisib | Duration of Response (DoR) | 143 days |
Primary
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.
Time frame: 7 Months
Population: Patients who received at least 1 dose of study medication and provided at least 1 post-baseline efficacy assessment
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Tenalisib | Overall Response Rate (ORR) | 33.3 percentage of participants |
Secondary
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.
Time frame: 7 Months
Population: Patients who received at least 1 dose of study medication
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Tenalisib | Number of Participants With Treatment-emergent Adverse Events as Assessed by CTCAE Criteria v5.0 | 15 participants |
Secondary
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.
Time frame: 7 months
Population: Patients who received at least 1 dose of study medication and provide at least 1 post-baseline efficacy assessment
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Tenalisib | Progression Free Survival (PFS) | 205 days |