A Phase 1 Study Evaluating the Safety and Pharmacokinetics of ABT-199 in Subjects With Relapsed or Refractory Chronic Lymphocytic Leukemia and Non-Hodgkin's Lymphoma
Diagnosis: Leukemia/MDS, Non-Hodgkin's Lymphoma
NCT ID: NCT01328626
(View complete trial on ClinicalTrials.gov)
DFCI Protocol ID: 11-169
This is a Phase 1, open-label, multicenter study evaluating the safety and pharmacokinetics profile of ABT-199 under a once daily dosing schedule in approximately 72 subjects with relapsed or refractory chronic lymphocytic leukemia (CLL) and non-Hodgkin's Lymphoma (NHL). Two arms will be implemented for dose escalation: Arm A, CLL/small lymphocytic lymphoma (SLL) subjects, and Arm B, NHL subjects. The dose escalation phase for each arm will include approximately 24 subjects, with the objective of defining dose limiting toxicities (DLTs) and the maximum tolerated dose (MTD). Once the MTD is declared for an arm, approximately 12 additional subjects will be enrolled into the arm in an expanded safety cohort. In addition, subjects in the Arm B (NHL) dose escalation of the study will be evaluated for the food effect of ABT-199.
Dana-Farber Cancer Institute
Matthew Davids, MD,
Dana Farber Cancer Institute
Dana-Farber Cancer Institute:
Ilene Galinsky, 617-632-3902,
- Subject must be at least 18 years of age.
- Subject must have either:
- (Arm A) relapsed or refractory CLL/SLL and require treatment in the opinion of
the Investigator. Subject must have relapsed following or be refractory to
standard treatments such as fludarabine based regimens (F, FC, FR, FCR) or
alkylator (chlorambucil, bendamustine) based regimens. In addition, the subject
is unable to tolerate other available therapies or no other therapies are
- (Arm B) relapsed or refractory NHL and require treatment in the opinion of the
Investigator. Subject must have histologically documented diagnosis of NHL as
defined in the World Health Organization classification scheme, except as noted in
the exclusion criteria. Subject must have relapsed following or be refractory to
standard treatments such as R-CHOP, R-CVP, or fludarabine based regimens. In
addition, the subject is unable to tolerate other available therapies or no other
therapies are available. Subjects with other lymphoproliferative diseases can be
considered in consultation with the Abbott medical monitor.
- Subject has an Eastern Cooperative Oncology Group (ECOG) performance score less
than or equal to 1.
- Subject must have adequate bone marrow independent of growth factor support per
local laboratory reference range at Screening.
- Subject must have adequate coagulation, renal, and hepatic function, per
laboratory reference range at Screening.
- CLL subject has undergone an allogeneic or autologous stem cell transplant or NHL
subject has undergone an allogeneic stem cell transplant or has been diagnosed with
Post-Transplant Lymphoproliferative Disease, Burkitt's lymphoma, Burkitt-like
lymphoma, or lymphoblastic lymphoma/leukemia.
- Subject has tested positive for HIV (due to potential drug-drug interactions between
anti-retroviral medications and ABT-199, as well as anticipated ABT-199 mechanism
based lymphopenia that may potentially increase the risk of opportunistic infections
and potential drug-drug interactions with certain anti infective agents).
- Subject has a cardiovascular disability status of New York Heart Association Class
greater or equal to 2. Class 2 is defined as cardiac disease in which patients are
comfortable at rest but ordinary physical activity, results in fatigue, palpitations,
dyspnea or anginal pain.
- Subject has a significant history of 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.