Pharmacokinetics, Safety, and Efficacy of ASTX727 in Combination With Venetoclax in Acute Myeloid Leukemia (AML) (NCT04657081)
🩺 Plain-English Summary (8th-Grade Level)
The Phase 1 portion of this study is a single-arm, open-label, multicenter, non-randomized interventional study to evaluate the pharmacokinetic (PK) interaction, safety, and efficacy of ASTX727 when given in combination with venetoclax for the treatment of newly diagnosed acute myeloid leukemia (AML) in adults who are age 75 years or older, or who have comorbidities that preclude use of intensive induction chemotherapy. The primary purpose of the study is to rule out drug-drug interactions between ASTX727 and venetoclax combination therapy by evaluating area under the curve (AUC) and maximum plasma concentration (Cmax) exposure. The Phase 2 portion of the study is to assess the efficacy of ASTX727 and venetoclax when given in combination and to evaluate potential PK interactions. Phase 2 will follow the same overall study design as Phase 1 and has two parts, Part A and Part B.
Who can join: To join this study, participants generally need to meet the listed inclusion criteria (8 items) and avoid the listed exclusions (21 items).
Location: USC Norris Comprehensive Cancer Center — Los Angeles, California
📋 "Do I Qualify?" — 1-Minute Self Screener
Instant ChecklistCheck every box below. If you can check all of them, you may meet the study's basic screening requirements (final eligibility is confirmed by the site team).
Usually NOT eligible if any of the following apply:
- History of myeloproliferative neoplasm including myelofibrosis, essential thrombocythemia, polycythemia vera, chronic myeloid leukemia with or without BCR-ABL1 translocation and AML with BCR-ABL1 translocation.
- The following karyotype abnormalities: t(8;21), inv(16) or t(15;17), or other acute promyelocytic leukemia variants that remain sensitive to all-trans retinoic acid (ATRA) therapy.
- Known active central nervous system involvement from AML.
- Known human immunodeficiency virus (HIV) infection (due to potential drug-drug interactions between antiretroviral medications and venetoclax). Human immunodeficiency virus testing will be performed at Screening, only if indicated per local guidelines or institutional standards.
- Known active hepatitis B or C infection (detectable viral load). Hepatitis B or C testing will be performed at Screening, only if indicated per local guidelines or institutional standards.
- Severe hepatic impairment defined as: bilirubin \>1.5×upper limit of normal (ULN) for participants ≥75 years or \>3×ULN for participants \<75 years; or aspartate aminotransferase (AST)/serum glutamic oxaloacetic transaminase (SGOT) or alanine aminotransferase (ALT)/serum glutamic pyruvic transaminase (SGPT) \>3×ULN (unless considered to be due to leukemic organ involvement).
- Severe renal impairment defined as: calculated creatinine clearance or glomerular filtration rate \<30 mL/min.
- A malabsorption syndrome or other condition that precludes enteral route of administration.
- 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.
- Chronic respiratory disease that requires continuous oxygen, or significant history of renal, neurologic, psychiatric, endocrinologic, metabolic, immunologic, hepatic, cardiovascular disease, any other medical condition or known hypersensitivity to any of the study medications that in the opinion of the investigator would adversely affect his/her participating in this study.
- Clinically significant uncontrolled systemic infection requiring therapy (viral, bacterial, or fungal).
- History of other malignancies prior to study entry, with the exception of adequately treated in situ carcinoma of the breast or cervix uteri; localized basal cell carcinoma or squamous cell carcinoma of the skin; previous malignancy confined and surgically resected (or adequately treated and controlled with other modalities); and any early stage malignancy for which no definitive therapy is required.
🔍 Extracted verbatim from the official NIH eligibility criteria. Always confirm with the study coordinator.
📍 All Participating Trial Locations (34 Sites)
- USC Norris Comprehensive Cancer Center — Los Angeles, California
- Stanford University — Palo Alto, California
- Yale University — New Haven, Connecticut
- Baptist MD Anderson Cancer Center — Jacksonville, Florida
- Boca Raton Clinical Research — Plantation, Florida
- The University of Chicago Medical Center — Chicago, Illinois
- Indiana University Simon Cancer Center — Indianapolis, Indiana
- Tufts Medical Center — Boston, Massachusetts
- Massachusetts General Hospital — Boston, Massachusetts
- University of Massachusetts, Memorial Medical Center — Worcester, Massachusetts
- Health Midwest Ventures Group, Inc. — Kansas City, Missouri
- Hackensack University of Medical Center — Hackensack, New Jersey
- Roswell Park Comprehensive Cancer Center — Buffalo, New York
- Weill Cornell Medical College — New York, New York
- University of Rochester — Rochester, New York
- The Research Foundation of the State University of New York (SUNY) — Syracuse, New York
- East Carolina University — Greenville, North Carolina
- The Ohio State University — Columbus, Ohio
- Penn State Milton S. Hershey Medical Center — Hershey, Pennsylvania
- UPMC Hillman Cancer Center — Pittsburgh, Pennsylvania
- Vanderbilt University Medical Center — Nashville, Tennessee
- MD Anderson Cancer Center — Houston, Texas
- Baylor Scott & White Research Institute — Temple, Texas
- Seattle Cancer Care Alliance — Seattle, Washington
- University of Calgary - Health Sciences Centre — Calgary, Alberta
💰 Cost, Insurance & Patient Rights
- 100% Free Items: The investigational treatment and protocol-required procedures are supplied at zero cost by the sponsor.
- Routine Patient Care: Under federal law (ACA § 2709) and many state statutes, routine care costs are covered during participation.
- Voluntary Participation: You may withdraw at any time without affecting your standard medical care.