A Phase 1b Study of ABT-199 (GDC-0199) in Combination With Azacitidine or Decitabine in Treatment-Naive Subjects With Acute Myelogenous Leukemia Who Are Greater Than or Equal to 60 Years of Age and Who Are Not Eligible for Standard Induction Therapy
This is a Phase 1b, open-label, non-randomized, multicenter study to evaluate the safety and pharmacokinetics of orally administered ABT-199 combined with decitabine or azacitidine and the preliminary efficacy of these combinations. In addition, there is a drug-drug interaction (DDI) sub-study only at a single site, to assess the pharmacokinetics and safety of ABT-199 in combination with posaconazole.
60 Years and up
Accepting Healthy Volunteers?
- Subjects must have confirmation of Acute Myeloid Leukemia (AML) by WHO criteria and be ineligible for treatment with a standard cytarabine and anthracycline induction regimen due to co-morbidity or other factors.
- Subject must have received no prior treatment for AML with the exception of hydroxyurea
- Subjects must have Eastern Cooperative Oncology Group (ECOG) Performance Status of ) to 2 for subjects greater than or equal to 75 years of age, or 0 to 3 for subjects greater than or equal to 60 to 74 years of age
- Subject must have adequate kidney and liver function as described in the protocol
- Subject has received treatment with the following hypomethylating agent and/or chemo therapeutic agent for for an antecedent hematologic disorder (AHD) (Subjects may have been treated with other agents for AHD i.e., Myelodysplastic syndrome [MDS])
- Subject has history of Myeloproliferative Neoplasm (MPN).
- Subject has favorable risk cytogenetics as categorized by the National Comprehensive Cancer Network Guidelines Version 2, 2014 for AML.
- Subject has t(8;21), inv(16), t(16;16) or t(15;17) karyotype abnormalities.
- Subject has acute promyelocytic leukemia.
- Subject has known active central nervous system involvement with AML.
- Subject has received a strong and/or moderate CYP3A inducer within 7 days prior to the initiation of study treatment.
- Subject has a history of other malignancies .prior to study entry, with the exception of:
- Adequately treated in situ carcinoma of the cervix uteri or carcinoma in situ of breast;
- Basal cell carcinoma of the skin or localized squamous cell carcinoma of the skin;
- Previous malignancy confined and surgically resected (or treated with other modalities) with curative intent.
- Subject has a white blood cell count > 25 × 10^9/L. Note: Hydroxyurea is permitted to meet this criterion.