A Phase 2 Open-Label Study of the Efficacy of ABT-199 (GDC-0199) in Subjects With Relapsed or Refractory Chronic Lymphocytic Leukemia Harboring the 17p Deletion
- Subject must be greater than or equal to 18 years of age.
- Subject must have diagnosis of CLL that meets published 2008 IWCLL NCI-WG
(International Workshop for Chronic Lymphocytic Leukemia National Cancer
Institute-Working Group) criteria.
- Subject has an indication for treatment according to the 2008 IWCLL NCI WG
- Subject has clinically measurable disease;
- Subject must have relapsed or be refractory after receiving at least one prior
line of therapy (a line of therapy is defined as completing at least 2 cycles of
treatment for a given line of therapy);
- Subjects must have 17p deletion, assessed by central laboratory, and determined
by FISH using the Vysis CLL probe kit.
- Subject has an Eastern Cooperative Oncology Group (ECOG) performance score of less
than or equal to 2.
- Subject must have adequate bone marrow function at Screening as follows:
- Absolute Neutrophil Count (ANC) greater than or equal to 1000/μL, or
- For subjects with an ANC less than 1000/μL at Screening and bone marrow heavily
infiltrated with underlying disease (approximately 80% or more),
granulocyte-colony stimulating factor (G-CSF) may be administered after
Screening and prior to the first dose of ABT-199 to achieve the ANC eligibility
criteria (greater than or equal to 1000/μL);
- Platelets greater than 40,000/mm3 (entry platelet count must be independent of
transfusion within 14 days of Screening);
- Hemoglobin greater than or equal to 8.0 g/dL.
- Subject must have adequate coagulation, renal, and hepatic function, per laboratory
reference range at Screening as follows:
- Activated partial thromboplastin time (aPTT) and prothrombin time (PT) not to
exceed 1.5 × the upper limit of normal;
- Calculated creatinine clearance greater than 50 mL/min using the Cockcroft-Gault
equation or a 24-hour urine collection for Creatinine Clearance;
- Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) less than or
equal to 3.0 × the upper normal limit of institution's normal range; Bilirubin
less than or equal to 1.5 × upper limit of normal. Subjects with Gilbert's
Syndrome may have a bilirubin greater 1.5 × upper limit of normal, per
discussion between the investigator and AbbVie medical monitor.
- For subjects at high risk of tumor lysis syndrome a pre-approval by the AbbVie
medical monitor is required prior to enrollment.
- Subject has undergone an allogeneic stem cell transplant.
- Subject has developed Richter's transformation.
- Subject has active and uncontrolled autoimmune cytopenias (for 2 weeks), including
autoimmune hemolytic anemia and idiopathic thrombocytopenic purpura.
- Subject has previously received ABT-199.
- Subject has received a biologic agent for anti-neoplastic intent within 8 weeks prior
to the first dose of study drug.
- Subject has received any of the following within 14 days prior to the first dose of
study drug, or has not recovered to less than Common Toxicity Criteria (CTC) grade 2
clinically significant adverse effect(s)/toxicity(s) of the previous therapy:
- Any anti-cancer therapy including chemotherapy, or radiotherapy;
- Investigational therapy, including targeted small molecule agents.
- Subject has known allergy to both xanthine oxidase inhibitors and rasburicase.