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 >/= 60 Years of Age and Who Are Not Eligible for Standard Induction Therapy
This is a 2 part study: dose escalation and dose expansion. The goal of Part 1 (dose escalation) of this clinical research study is to find the highest tolerable dose of venetoclax (ABT-199) when given in combination with either decitabine or azacitidine in patients who have AML and are 65 years of age or older. The safety of this drug combination will also be studied. The goal of Part 2 (dose expansion) of this clinical research study is to learn if the highest tolerable dose of venetoclax and either decitabine or azacitidine found in Part 1 can help to control AML.The study doctor will discuss this in more detail with you. This consent form is for Part 1 only. MD Anderson will only be enrolling participants to receive Venetoclax and decitabine. The safety of venetoclax will be studied in both parts of this study.
Disease Group: Leukemia
Treatment Agent: Azacitidine,Decitabine
Treatment Location: Both at MDACC & and Other Sites
The primary objective is to evaluate the safety and pharmacokinetics of venetoclax administered orally in combination with decitabine or azacitidine in treatment naïve subjects with Acute Myelogenous Leukemia (AML) who are greater than or equal to 65 years of age and who are not eligible for standard induction therapy due to co-morbidity or other factors. Secondary objectives include assessing the preliminary efficacy of venetoclax administered orally in combination with either decitabine or azacitidine in this patient population. Exploration of biomarkers that may serve as surrogates for clinical endpoints for future venetoclaxcombinations or single agent studies may be performed.
IRB Review and Approval Date: 10/07/2014
Recruitment Status: Open
Projected Accrual: 214
1) Subject must be greater than or equal to 65 years of age.
2) Subject must have a projected life expectancy of at least 12 weeks.
3) Subject must have histological confirmation of AML and be ineligible for treatment with a standard cytarabine and anthracycline induction regimen due to co-morbidity or other factors.
4) Subject must have received no prior treatment for AML with the exception of hydroxyurea, allowed through the first cycle of study treatment. NOTE: Subject may have been treated for prior Myelodysplastic Syndrome (excluding hypomethylating agents).
5) Subject must have an Eastern Cooperative Oncology Group (ECOG) Performance status of 0 to 2.
6) Subject must have adequate renal function as demonstrated by a calculated creatinine clearance >/= 30 mL/min; determined via urine collection for 24-hour creatinine clearance or by the Cockcroft Gault formula.
7) Subject must have adequate liver function as demonstrated by: </= aspartate aminotransferase (AST) </= 2.5 × upper limit of normal (ULN)* </= alanine aminotransferase ULN per discussion between the investigator and AbbVie medical monitor (ALT) </= 2.5 × upper limit of normal (ULN)* bilirubin </= 1.5 × upper limit of normal(ULN)* * unless considered due to leukemic organ involvement. Note: Subjects with Gilbert's Syndrome may have a bilirubin >/= 1.5 × upper limit of normal (ULN) per discussion between the investigator and AbbVie medical monitor
8) Male subjects must agree to refrain from unprotected sex and sperm donation from initial study drug administration until 90 days after the last dose of study drug.
9) 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.
1) Subject has received treatment with hypomethylating agent and/or
cytarabine for a pre-existing myeloid disorder.
2) Subject must not have good risk cytogenetics as categorized by the National Comprehensive Cancer Network (NCCN) Guidelines Version 2, 2014 for Acute Myeloid Leukemia
3) Subject has t(8;21), inv(16) or t(15;17) karyotype abnormalities.
4) Subject has acute promyelocytic leukemia (French-American-British Class M3 AML).
5) Subject has known active central nervous system (CNS) involvement from AML.
6) Subject has tested positive for Human Immunodeficiency Virus HIV (due to potential drug-drug interactions between antiretroviral medications and venetoclax , as well as anticipated venetoclax mechanism-based lymphopenia that may potentially increase the risk of opportunistic infections). Note: Human Immunodeficiency Virus (HIV) testing is not required.
7) Subject 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; ? Warfarin or requires the use of warfarin (due to potential drug-drug interactions that may potentially increase the exposure of warfarin and complications of this effect).
8) Subject has received the following within 5 days prior to the initiation of study treatment: ? CYP3A inhibitors such as fluconazole, ketoconazole, and clarithromycin.
9) Subject has consumed grapefruit, grapefruit products, Seville oranges (including marmalade containing Seville oranges) or Star fruit within 3 days prior to the initiation of study treatment.
10) Subject has a cardiovascular disability status of New York Heart Association Class >/= 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.
11) Subject 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.
12) Subject has chronic respiratory disease that requires continuous oxygen use.
13) Subject has a malabsorption syndrome or other condition that precludes enteral route of administration.
14) Subject exhibits evidence of other clinically significant uncontrolled condition(s) including, but not limited to: ? Uncontrolled systemic infection requiring IV therapy (viral, bacterial or fungal).
15) Subject 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; ? Previous malignancy confined and surgically resected (or treated with other modalities) with curative intent.
16) Subject has a white blood cell count >/= 25 × 109/L. Note: Hydroxyurea is permitted to meet this criterion.
17) Subject is a candidate for a bone marrow or stem cell transplant within 12 weeks after study enrollment.
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