A Study Evaluating ABT-199 in Combination With Low-Dose Cytarabine in Treatment-Naïve Subjects With Acute Myelogenous Leukemia (AML)
Acute Myelogenous Leukemia - AML
Conditions: official terms
Leukemia - Leukemia, Myeloid - Leukemia, Myeloid, Acute
Conditions: Keywords
Myelogenous Leukemia, Untreated AML, Treatment Naive AML
Study Type
Study Phase
Phase 1
Study Design
Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Name: ABT-199 Type: Drug
Name: Cytarabine Type: Drug
Overall Status
This study consists of two phases: a Phase 1, or dose-escalation portion, that will evaluate the safety and pharmacokinetic profile of ABT-199 in combination with low-dose cytarabine (LDC), define the maximum tolerated dose (MTD), and generate data to support a recommended Phase 2 dose (RPTD) in treatment-naïve subjects with Acute Myelogenous Leukemia (AML); and a subsequent Phase 2 that will evaluate if the RPTD has sufficient efficacy and acceptable toxicity to warrant further development of the combination therapy.
Criteria for eligibility
Healthy Volunteers: No
Maximum Age: N/A
Minimum Age: 65 Years
Gender: Both
Criteria: Inclusion Criteria:

- Participant must have a projected life expectancy of at least 12 weeks.

- Participant must have histological confirmation of Acute Myelogenous Leukemia (AML) and be ineligible for treatment with a standard cytarabine and anthracycline induction regimen due to co-morbidity or other factors.

- Participant must not have received prior treatment for AML with the exception of hydroxyurea, allowed through the first cycle of study treatment. Participant may have been treated for prior Myelodysplastic Syndrome.

- Participant must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2.

- Participant must have adequate renal and liver function.

- Male participants must agree to refrain from unprotected sex and sperm donation from initial study drug administration until 180 days after the last dose of study drug.

Exclusion Criteria:

- Participant has received treatment with cytarabine for a pre-existing myeloid disorder.

- Participant has acute promyelocytic leukemia (French-American-British Class M3 AML).

- Participant has known active central nervous system (CNS) involvement with AML.

- Participant has tested positive for human immunodeficiency virus (HIV).

- Participant has received the following within 7 days prior to the initiation of study treatment: potent CYP3A inducers such as rifampin, carbamazepine, phenytoin, and St. John's wort; or warfarin or requires the use of warfarin

- Participant has received the following within 5 days prior to the initiation of study treatment: CYP3A inhibitors such as fluconazole, ketoconazole, and clarithromycin.

- Participant has consumed grapefruit, grapefruit products, Seville oranges (including marmalade containing Seville oranges) or Starfruit within 3 days prior to the initiation of study treatment.

- Participant has a cardiovascular disability status of New York Heart Association Class ≥ 2.

- Participant has a significant history of renal, neurologic, psychiatric, endocrinologic, metabolic, immunologic, hepatic, cardiovascular disease, or any other medical condition that in the opinion of the investigator would adversely affect his/her participating in this study.

- Participant has chronic respiratory disease that requires continuous oxygen use.

- Participant has a malabsorption syndrome or other condition that precludes enteral route of administration.

- Participant exhibits evidence of other clinically significant uncontrolled condition(s) including, but not limited to: uncontrolled systemic infection requiring IV therapy (viral, bacterial or fungal).

- Participant has a history of other malignancies prior to study entry, with the exception of: adequately treated in situ carcinoma of the breast or cervix uteri; basal cell carcinoma of the skin or localized squamous cell carcinoma of the skin; or previous malignancy confined and surgically resected (or treated with other modalities) with curative intent.

- Participant has a white blood cell count > 25 × 10^9/L. Hydroxyurea is permitted to meet this criterion.

- Participant is a candidate for a bone marrow or stem cell transplant within 12 weeks after study enrollment.
Site Reference ID/Investigator# 131175
Westwood, Kansas, United States
Status: Recruiting
Site Reference ID/Investigator# 131171
Ann Arbor, Michigan, United States
Status: Recruiting
Site Reference ID/Investigator# 131170
New York, New York, United States
Status: Not yet recruiting
Site Reference ID/Investigator# 131168
Pittsburgh, Pennsylvania, United States
Status: Recruiting
Site Reference ID/Investigator# 131178
Seattle, Washington, United States
Status: Recruiting
Site Reference ID/Investigator# 131180
Melbourne, Australia
Status: Recruiting
Site Reference ID/Investigator# 133979
Hamburg, Germany
Status: Not yet recruiting
Site Reference ID/Investigator# 131183
Bologna, Italy
Status: Recruiting
Start Date
January 2015
Completion Date
October 2017
Record processing date
ClinicalTrials.gov processed this data on July 28, 2015
ClinicalTrials.gov page