Chronic Lymphocytic Leukemia, Non Hodgkin Lymphoma
Conditions
Keywords
APG-2575, B-cell lymphoma 2 (BCL-2), Chronic lymphocytic leukemia, non-hodgkin's lymphoma
Brief summary
The purpose of this study is to assess the safety, tolerability, pharmacokinetic and pharmacodynamic properties of APG-2575 in patients with relapse or refractory chronic lymphocytic leukemia and non-hodgkin's lymphoma.
Detailed description
This is a multi-center, single-agent, open-label, Phase I study of APG-2575. The study consists of the dose escalation stage and the dose expansion stage. APG-2575 will be administered orally, once daily for consecutive 4 weeks as one cycle. Initially, the start dose is 20mg. Single patient cohorts will be evaluated, the dose of APG-2575 will be increased in subsequent cohorts, to 50 mg, 100 mg, 200 mg, 400 mg, 600mg and 800mg accordingly. If there is any one of the following event is observed, a dose-limiting toxicity (DLT), two drug related Grade 2 toxicities or one drug related ≥ Grade 3 toxicity, or laboratory or clinical tumor lysis syndrome (TLS), or suspected hypersensitivity reaction occur in Cycle 1, the dose escalation will convert to the standard 3+3 design, If ≥ 2/6 patients develop DLT at any dose level dose escalation will cease and the dose level immediately below will be expanded to 6 patients. If ≤ 1/6 patients develop a DLT at the highest dose reached this will be declared the MTD. After the MTD/Recommended Phase II Dose (RP2D) is defined, a maximum of 40 patients will be treated at that dose level.
Interventions
DRUGAPG-2575
Multiple dose cohorts, PO, every day (QD) of a 28-day cycle
Sponsors
Suzhou Yasheng Pharmaceutical Co., Ltd.
Ascentage Pharma Group Inc.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Age ≥18 years old. 2. Histologically confirmed diagnosis of chronic lymphocytic leukemia, or non-Hodgkin's lymphoma such as mantle cell lymphoma, diffuse large B cell lymphoma, Waldenstrom macroglobulinemia (WM). 3. Patient must have relapsed or refractory to, intolerant to, or are considered ineligible for therapies known to provide clinical benefit. 4. Life expectancy ≥ 3 months. 5. Eastern Cooperative Oncology Group (ECOG) Performance Status (PS): 0 -1 in dose escalation; 0-2 in dose expansion. 6. Corrected QT interval ≤450ms in males, and ≤470ms in females. 7. Adequate bone marrow function independent of growth factor: 1. Absolute neutrophil count (ANC) ≥1.0 X 10E9/L. 2. Hemoglobin ≥ 8.0 g/dL. 3. Platelets count ≥ 30 X 10E9/L (entry platelet count must be independent of transfusion within 7 days of first dose). 8. Adequate renal and liver function as indicated by: 1. Serum creatinine ≤ 1.5 x upper limit of normal (ULN); if serum creatinine is \>1.5 X ULN, creatinine clearance must be ≥60 mL/min. 2. Total bilirubin ≤1.5 x ULN, except subject with known Gilbert's syndrome. 3. Aspartate aminotransferase (AST) and Alanine aminotransferase (ALT) \<2.5 x ULN. 4. Alkaline phosphatase \< 2.5 x ULN and \< 5 x for bone metastases &/or no hepatic parenchymal metastases on screening radiographic examination. 5. Thromboplastin time (aPTT)≤1.5 X ULN unless the subject is receiving anticoagulant therapy as long as prothrombin time (PT) or aPTT is within therapeutic range of intended use of anticoagulants. 9. Willingness by both males, and female patients of child bearing potential, to use contraception by a method that is deemed effective by the investigator, throughout the treatment period and for at least three months following the last dose of study drug Postmenopausal women must be amenorrheal for at least 12 months to be considered of non-childbearing potential. All partners must have the same willingness for contraception methods throughout the treatment period and for at least three months following the last dose of study drug as well. 10. Ability to understand and willingness to sign a written informed consent form (the consent form must be signed by the patient prior to any study-specific procedures). 11. Willingness and ability to comply with study procedures and follow-up examination.
Exclusion criteria
Patients who meet any of the following
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Maximum Tolerated Dose (MTD) | 28 days | Patients with APG-2575 treatment related adverse events (AE), serious adverse events (SAE) will be assessed according NCI CTCAE Version 5.0 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Maximum plasma concentration (Cmax) | 28 days | Maximum plasma concentration (Cmax) will be assessed in the patients treated with APG-2575 |
| Area under the plasma concentration versus time curve (AUC) | 28 days | Area under the plasma concentration versus time curve (AUC) of APG-2575 will be assessed in the patients treated with APG-2575 |
| Anti-tumor effects of APG-2575 | up to 3 years | Response will be evaluated every 2 cycles (8 weeks), by the investigator based on disease specific criteria. |
Countries
China
Outcome results
None listed