INCLUSION CRITERIA:
A subject will be eligible for study participation if he/she meets the following criteria:
1. Subject must be greater than or equal to 18 years of age.
2. Subject has a non-hematologic malignancy (radiographic, histologic, or cytologic confirmation), or hematologic malignancy (histologic or cytologic confirmation) that is relapsed or refractory to standard therapy, or for which no known effective therapy exists.
3. In the investigator's opinion, the subject's life expectancy is at least 90 days.
4. Subject has received at least 1 but no more than 3 prior chemotherapy treatment regimens.
5. If clinically indicated, (e.g., subjects over the age of 70) subjects must have documented brain imaging (MRI or CT) negative for subdural or epidural hematoma within 28 days prior to the first dose of study drug.
6. Subject has an Eastern Cooperative Oncology Group (ECOG) performance score of less than or equal to 1.
7. Subject must have adequate bone marrow, renal and hepatic function per local laboratory reference range as follows:
- Bone marrow: Absolute Neutrophil count (ANC) greater than or equal to 1,000/microl; Platelets greater than or equal to 100,000/mm(3); Hemoglobin greater than or equal to 9.0 g/dL;
- Renal function: serum creatinine less than or equal to 2.0 mg/dL or calculated creatinine clearance greater than or equal to 50;
- Hepatic function and enzymes: AST and ALT less than or equal to 3.0 times the upper normal limit (ULN) of institution's normal range; Bilirubin less than or equal to 1.5 times ULN.
Subjects with Gilbert's Syndrome may have a Bilirubin greater than 1.5 times ULN;
- Coagulation: aPTT, PT not to exceed 1.2 times ULN.
8. Female subjects must be surgically sterile, postmenopausal (for at least one year), or have negative results for a pregnancy test performed as follows:
- At Screening on a serum sample obtained within 14 days prior to initial study drug administration, and
- Prior to start of dosing on a urine sample if it has been greater than 7 days since obtaining the serum pregnancy test results.
9. Female subjects not surgically sterile or postmenopausal (for at least one year) and non-vasectomized male subjects must practice at least one of the following methods of birth control:
- total abstinence from sexual intercourse (minimum one complete menstrual cycle prior to starting study drug);
- a vasectomized partner;
- hormonal contraceptives (oral, parenteral or transdermal) for at least three months prior to study drug administration;
- double-barrier method (including condoms, contraceptive sponge, diaphragm or vaginal ring with spermicidal jellies or cream).
10. Subject must voluntarily sign and date an informed consent, approved by an Independent Ethics Committee (IEC)/Institutional Review Board (IRB), prior to the initiation of any screening or study-specific procedures.
EXCLUSION CRITERIA:
A subject will not be eligible for study participation if he/she meets any of the following criteria:
1. Subject has a history of or is clinically suspicious for cancer-related central nervous system (CNS) disease.
2. Subject has undergone an allogeneic stem cell transplant.
3. Subject has an underlying, predisposing condition of bleeding or currently exhibits signs of bleeding. The subject has a recent history of non-chemotherapy induced thrombocytopenic associated bleeding within one year prior to the first dose of study drug.
4. Subject has active peptic ulcer disease or other hemorrhagic esophagitis/gastritis.
5. Subject has active immune thrombocytopenic purpura or a history of being refractory to platelet transfusions (within 1 year prior to the first dose of study drug).
6. Subject has a significant history of cardiovascular disease (e.g., MI, thrombotic or thromboembolic event in the last 6 months), renal, neurologic, psychiatric, endocrinologic, metabolic, immunologic, or hepatic disease that in the opinion of the investigator would adversely affect his/her participating in this study.
Questions regarding inclusion of individual subjects should be directed to the Abbott Medical Monitor or designee.
7. Female subject is pregnant or breast-feeding.
8. Subject has a history of or an active medical condition(s) that affects absorption or motility (e.g., Crohn's disease, celiac disease, gastroporesis, short bowel syndrome, etc).
9. Subject has tested positive for HIV (due to potential drug-drug interactions between anti-retroviral inhibitors and ABT-263, as well as anticipated ABT-263 mechanism based lymphopenia that may potentially increase the risk of opportunistic infections and potential drug-drug interactions with certain antiinfective agents).
10. Subject exhibits evidence of other clinically significant uncontrolled condition(s) including, but not limited to:
- active systemic fungal infection;
- diagnosis of fever and neutropenia within one week prior to study drug administration.
11. Subject has received steroid therapy within seven days prior to the first dose of study drug for anti-neoplastic intent.
12. Subject has received any anti-cancer therapy including chemotherapy, immunotherapy, radiotherapy, hormonal (with the exception of hormones for hypothyroidism or estrogen replacement therapy [ERT]), or any investigational therapy within 14 days prior to the first dose of study drug, or has not recovered to less than grade 2 clinically significant adverse effect(s)/toxicity(s) of the previous therapy.
13. Subject has received a biologic agent within 30 days prior to the first dose of study drug.
14. Subject is currently receiving or requires anticoagulation therapy or any drugs or herbal supplements that affect platelet function, with the exception of low-dose anticoagulation medications that are used to maintain the patency of a central venous catheter.
15. Subject has received aspirin within seven days prior to the first dose of study drug and during ABT-263 administration.
16. Subject has consumed grapefruit or grapefruit products within 3 days prior to the first dose of study drug.
17. In the opinion of the investigator, the subject is an unsuitable candidate to receive ABT-263. Subjects considered to be at high risk for developing tumor lysis syndrome should have provisions made to closely monitor the subject following the first dose of study drug and during ABT-263 administration.
National Institutes of Health Clinical Center
Bethesda, Maryland 20892. Last update: 01/30/2009