| Eligibility |
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 exclusion criteria are not to be enrolled in this
study:
1. Prior history of allogeneic cell transplant.
2. Subjects have been diagnosed with Burkitt's lymphoma, Burkitt-like lymphoma, or
lymphoblastic lymphoma/leukemia.
3. Received chemotherapy within 14 days prior to entering the study.
4. Received biologic (< 28 days), small molecule targeted therapies (< 5 half-life) or
other anti-cancer therapy within 21 days of study entry.
5. Concurrent treatment with an investigational agent, 14 days for small molecular agents
and/or 28 days for biologics treatment prior to the first dose of therapy.
6. Radiation within 14 days of study entry, thoracic radiation within 28 days of study
entry.
7. Has gastrointestinal conditions that could affect the absorption of APG-2575 in the
opinion of the Investigator.
8. Has known active central nervous system (CNS) involvement.
9. Continuance of toxicities due to prior radiotherapy or chemotherapy agents that do not
recover to = Grade 1 except alopecia or neuropathy.
10. Failure to recover adequately, as judged by the investigator, from prior surgical
procedures. Patients with active wound healing, patients who have had major surgery
within 28 days from study entry, and patients who have had minor surgery within 14
days of study entry.
11. Unstable angina, myocardial infarction, or a coronary revascularization procedure
within 180 days of study entry.
12. Active rheumatoid arthritis (RA), active inflammatory bowel disease, or any other
disease or condition associated with chronic inflammation.
13. Active infection requiring systemic antibiotic/ antifungal medication, known
clinically active hepatitis B or C infection, or known HIV disease.
14. Known or suspected Wilson's Disease, or other conditions that affect copper
accumulation or regulation.
15. Uncontrolled concurrent illness including, but not limited to: symptomatic congestive
heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric
illness/social situations that would limit compliance with the study requirements.
16. The last treatment for the subject before signing the informed consent was bcl-2
targeted drug treatment (if the subject had received bcl-2 inhibitor treatment but did
not develop drug resistance, it could be included in this study).
17. History of secondary active malignancies within the past 2 years. However, adequately
treated superficial skin cancer other than melanoma, in-situ cervix cancer more than 4
weeks, or prostate cancer not requiring any treatment and under surveillance prior to
enrollment will not be considered exclusionary.
18. Known to be allergic to study drug ingredients or their analogues.
19. Pregnancy or lactation, or pregnancy is expected during the study period or within 3
months after the last administration of APG-2575.
20. Any other condition or circumstance that would, in the opinion of the investigator,
make the patient unsuitable for participation in the study.
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