A Phase 2, Open label Study to Assess the Efficacy and Safety of Tenalisib(RP6530) in Patients with Relapsed/Refractory Chronic LymphocyticLeukemia (CLL)
- Conditions
- Relapsed/Refractory Chronic Lymphocytic Leukemia (CLL)MedDRA version: 21.0Level: LLTClassification code 10008976Term: Chronic lymphocytic leukemiaSystem Organ Class: 100000004864Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2019-003622-25-PL
- Lead Sponsor
- Rhizen Pharmaceuticals SA
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 61
Patients must meet all the following inclusion criteria to be eligible for participation in this study:
1. Patients with diagnosis of B-cell CLL as confirmed by histopathology or flow cytometry.
2. Disease status defined as refractory to or relapsed after at least one prior therapy.
3. Presence of measurable lymphadenopathy, defined as the presence of > 1 nodal lesion that measures = 1.5 cm in the longest diameter (LD) as assessed by computed tomography (CT).
4. ECOG performance status = 2.
5. Male or female = 18 years of age.
6. Life expectancy of at least 3 months.
7. Adequate bone marrow (BM), liver, and renal function as assessed by the following laboratory requirements conducted within 14 calendar days before starting study treatment.
a. Adequate bone marrow function.
I. Haemoglobin = 9 g/dl
II. Absolute neutrophil count (ANC) = 1 x 10^9/L
III. Platelets =50 x 10^9/L
Patients with hemoglobin, neutrophil and platelet counts below the above specified values will be eligible if it is due to tumor dissemination or infiltration to bone marrow and as per physician’s discretion. Hemoglobin and platelet requirements should not be met by use of recent transfusion or growth factor support (G-CSF or erythropoietin) within 3 weeks prior to assessment.
b. Adequate liver function.
I. Total bilirubin =1.5 times the upper limit of normal (ULN)
II. ALT and AST should be = 3 x ULN. ALT and AST = 5 x ULN if known liver involvement.
c. Adequate renal function: Calculated creatinine clearance = 50 mL/min (as calculated by the Cockcroft-Gault method) or Creatinine = 1.5 mg/dl.
8. Ability to swallow and retain oral medication.
9. Female patients who are not of child-bearing potential, and female patients of child-bearing potential should have a negative serum pregnancy test within 3 days prior to Cycle 1 Day 1 (C1D1). Female patients of child-bearing potential must consent to use a medically acceptable method of contraception as defined in Appendix A , throughout the study period and for 30 days after the last dose of study drug.
10. Male patients willing to use adequate contraceptive measures throughout the study period and for 12 weeks after the last dose of Tenalisib.
11. Willingness and ability to comply with trial and follow-up procedures and give written informed consent.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 20
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 41
1. Patient with Richter’s (large cell) transformation, or prolymphocytic leukemia (PLL) transformation.
2. Patients receiving any cancer therapy (i.e., chemotherapy, radiation therapy, immunotherapy and biologic therapy) or any cancer investigational drug within 3 weeks (21 days) or 5 half-lives (whichever is shorter) prior to C1D1.
3. Prior exposure to drug that specifically inhibits PI3K (e.g. idelalisib, copanlisib, duvelisib, umbralisib)
4. Patient with autologous / allogeneic stem cell transplant (ASCT/Allo-SCT) receiving treatment for active graft versus-host disease (GVHD).
5. Evidence of ongoing severe systemic bacterial, fungal or viral infection as assessed by the investigator.
6. Central nervous system (CNS) involvement of leukemia or lymphoma
7. Ongoing immunosuppressive therapy including systemic corticosteroids except as allowed per concomitant medication (Section 5.2).
8. Known history of severe liver injury including drug-induced liver injury (e.g. alcoholic liver disease, primary biliary cirrhosis, ongoing extrahepatic obstruction caused by stones, cirrhosis of the liver or portal hypertension) as judged by investigator;
9. Any severe and/or uncontrolled medical conditions or other conditions that could affect patient participation in the study, as judged by investigator, such as:
a. Symptomatic or history of documented congestive heart failure (New York heart association (NYHA) functional classification III-IV)
b. Myocardial infarction within 6 months of C1D1
c. QTcF >470 msec.
d. Angina not well-controlled by medication.
e. Poorly controlled atherosclerotic vascular disease (e.g. cerebrovascular accident, transient ischemic attack, angioplasty, cardiac/vascular stenting).
10. Patient treated for other malignancy in last 3 years of study enrollment except for adequately treated basal, squamous cell carcinoma or non-melanomatous skin cancer, carcinoma in situ of the cervix, superficial bladder cancer not treated with intravesical chemotherapy or BCG within 6 months; and localized prostate cancer with PSA <1.0 mg/dL within 4 weeks of C1D1.
11. Women who are pregnant or lactating.
12. Known seropositive requiring anti-viral therapy for human immunodeficiency virus (HIV) infection.
13. Known seropositive requiring anti-viral therapy for hepatitis B virus (HBV) infection OR evidence of active hepatitis B infection as defined by detectable viral load if the antibody tests are positive. [Note: Subject with a positive HBcAb with an undetectable/negative hepatitis B DNA test (e.g., polymerase chain reaction [PCR] test) can be enrolled].
14. Known seropositive requiring anti-viral therapy for hepatitis c virus (HCV) infection OR patients with positive hepatitis C virus Ab with detectable viral load. [Note: Subject with a positive HCV with an undetectable/negative hepatitis C RNA test (e.g., PCR) can be enrolled].
15. Known seropositive requiring anti-viral therapy for active CMV infection (Note: A serology positive CMV subject with negative CMV PCR test will be enrolled).
16. Unresolved NCI-CTCAE grade 2 and above toxicity (except as mentioned in adequate organ function (Refer inclusion criteria #7) attributed to any prior therapy/procedure excluding alopecia.
17. Inability or unwillingness to comply with study and/or follow-up procedures outlined in the protocol;
18. Concurrent condition that in the investigator’s opinion would jeopardize compliance with the protocol.
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: To assess the anti-tumor activity of Tenalisib as determined by the<br>objective response rate (ORR) and duration of response (DoR);Secondary Objective: • To characterize safety and tolerability of Tenalisib.<br>• To assess progression free survival (PFS);Primary end point(s): Efficacy:<br>• Overall response rate (ORR): ORR is defined as sum of complete<br>response (CR) and partial response (PR) rates as defined by iwCLL<br>guideline for CLL (Hallek et al. 2018).<br>• Duration of response (DoR): DoR is defined as the interval from the<br>first documentation of CR/PR to first documentation of definitive disease<br>progression or death from any cause.<br>• Progression-free survival (PFS): PFS is defined as the interval from<br>first dose to first documentation of definitive disease progression or<br>death from any cause.<br>Safety:<br>• Adverse Event (AE), Grade 3/ 4 AEs, Serious Adverse Event (SAE).;Timepoint(s) of evaluation of this end point: End of Treatment
- Secondary Outcome Measures
Name Time Method Secondary end point(s): To characterize safety and tolerability of Tenalisib.<br>To assess progression free survival (PFS).;Timepoint(s) of evaluation of this end point: End of Treatment