TL-895 in B cell malignancies and Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma
- Conditions
- B Cell Malignancies and Chronic Lymphocytic Leukemia or Small Lymphocytic LymphomaMedDRA version: 20.0Level: HLTClassification code 10003900Term: B-cell lymphomas NECSystem Organ Class: 100000004851MedDRA version: 21.0Level: LLTClassification code 10008976Term: Chronic lymphocytic leukemiaSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)MedDRA version: 21.1Level: PTClassification code 10003908Term: B-cell small lymphocytic lymphomaSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2016-000286-23-HU
- Lead Sponsor
- Telios Pharma, Inc.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- All
- Target Recruitment
- 30
1. Adults =18 years of age
2. Subject population (relapsed/refractory CLL or relapsed/refractory SLL)
3. ECOG performance status of = 2
4. Adequate hematological function independent of growth factor support for at least 7 days with the exception of pegylated G-CSF and darbepoetin which require at least 14 days, defined as
a. Absolute neutrophil count (ANC) = 1.0 × 109/L
b. Platelet count = 50 × 109/L or = 25 × 109/L if thrombocytopenia is related to CLL/SLL
5. Adequate hepatic function defined by:
a. Total bilirubin = 2x upper limit of normal (ULN). Subjects with known Gilbert's Syndrome or disease-related
hemolysis must have a total bilirubin = 3x ULN.
b. AST = 2.5 × ULN, and ALT = 2.5 × ULN.
6. Adequate renal function defined by an estimated creatinine clearance = 30 mL/min according Cockcroft Gault
7. Female subjects of childbearing potential and their male partners, or male subjects who have female partners of childbearing potential, must both use a highly effective contraception method during the study.
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 28
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 12
Dose Expansion (Part 2)
To be eligible for inclusion in the dose expansion part of this trial, subjects must not meet any of the following criteria:
1. Prior anticancer treatment with any BTK or PI3K inhibitor
2. Known history of central nervous system lymphoma or leukemia
3. History of Richter’s transformation or prolymphocytic leukemia
4. Prior therapy with:
• Anticancer treatment with chemotherapy, immunomodulating therapy, biologic therapy,
radiation therapy, or with any other anticancer therapy within 28 days prior to first dose of study treatment.
• Any investigational agent within 28 days prior to first dose of study treatment. Participation in observational study is permitted.
• Allogeneic stem cell transplant or active graft versus host disease following allogeneic transplant within 6 months prior to first dose of study treatment.
• Autologous stem cell transplant within the last 3 months prior to first dose of study treatment.
5. Subjects with a history of bleeding diathesis or major hemorrhage (unrelated to trauma) within 6 months prior to first dose of study treatment
6. History of stroke or intracranial hemorrhage within 6 months prior to first dose of study treatment.
7. Received major surgical intervention within 28 days prior to first dose of study treatment, or history of major organ transplant.
8. Having history of difficulty of swallowing, gastric or small bowel surgery with history of malabsorption or other chronic gastrointestinal disease or conditions that may hamper compliance and/or absorption of the study treatment.
9. Uncontrolled intercurrent illness including, but not limited to clinically significant cardiac disease (New York Heart Association Class III or IV); symptomatic congestive heart failure; unstable angina pectoris; unstable ventricular arrhythmia; or psychiatric illness/social situations that would limit compliance with study requirements.
10. Grade 2 or higher QTc prolongation (> 480 milliseconds per National Cancer Institute Common Terminology of Adverse Events [v 5.0]).
11. Subjects with uncontrolled bacterial, fungal, parasitic, or viral infection. Subjects with acute bacterial infections requiring antibiotic use should not enroll until the infection is stable in the judgement of the treating physician; these subjects may be on antibiotics at time of screening
12. Subjects with active hepatitis B virus (HBV) or hepatitis C virus (HCV)
13. Subjects with known history of human immunodeficiency virus (HIV)
14. Other malignancy within the last 3 years, other than curatively treated basal cell or squamous cell skin cancer, carcinoma in situ of the cervix, organ-confined or treated nonmetastatic prostate cancer with normal prostate-specific antigen, in situ breast carcinoma after complete surgical resection, or superficial transitional cell bladder carcinoma.
15. Requires or receiving anticoagulation with warfarin or equivalent vitamin K antagonists (eg, phenprocoumon) within 7 days of first dose of study drug.
16. Requires treatment with proton-pump inhibitors (e.g., omeprazole, esomeprazole, lansoprazole, dexlansoprazole, rabeprazole, or pantoprazole). Subjects receiving proton-pump inhibitors who switch to H2-receptor antagonists or antacids are eligible for enrollment in this study. Proton-pump inhibitors must be stopped at least 5 days prior to the first dose of TL-895.
17. Women who are pregnant or breastfeeding.
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: For dose expansion, Part 2:<br>To determine the overall response rate (ORR) based on International Workshop on Chronic Lymphocytic Leukemia (iwCLL) response criteria per Investigator assessment;Secondary Objective: For dose expansion, Part 2:<br>- To determine the complete response (CR)/complete response with incomplete bone marrow recovery (CRi) rate <br>- To assess the efficacy of TL-895 by DOR<br>- To evaluate the safety and tolerability of TL-895 <br>- To characterize the PK profile of TL-895 <br>- To evaluate the effect of TL-895 on BTK occupancy in PBMCs ;Primary end point(s): Dose Expansion, Part 2<br>- ORR, defined as the proportion of subjects achieving CR, CRi, nodular partial response (nPR), partial response (PR), or PR with lymphocytosis (PR-L) at any time while on the study based on iwCLL response criteria (2), as assessed by investigators ;Timepoint(s) of evaluation of this end point: Part 2: Baseline up to end of study
- Secondary Outcome Measures
Name Time Method