Ph I Study of Alvocidib and Cytarabine/Daunorubicin (7+3) in Patients With Newly Diagnosed Acute Myeloid Leukemia (AML).
Acute Myeloid Leukemia
About this trial
This is an interventional treatment trial for Acute Myeloid Leukemia
Eligibility Criteria
Inclusion Criteria:
To be eligible for participation in the study, patients must meet all of the following inclusion criteria:
- Be between the ages of ≥18 and ≤65 years
- Have an established, pathologically confirmed diagnoses of AML by World Health Organization (WHO) criteria with ≥20% bone marrow blasts based on histology or flow cytometry
- Be newly diagnosed and previously untreated
- Have an Eastern Cooperative Oncology Group (ECOG) performance status (PS) ≤2
- Have a serum creatinine level ≤1.8 mg/dL
- Have an alanine aminotransferase (ALT) and aspartate aminotransferase (AST) level ≤5 times upper limit of normal (ULN)
- Have a total bilirubin level ≤2.0 mg/dL (unless secondary to Gilbert syndrome, hemolysis, or leukemia)
- Have a left ventricular ejection fraction (LVEF) >45% by echocardiogram (ECHO) or multigated acquisition (MUGA) scan
- Be nonfertile or agree to use an adequate method of contraception. Sexually active patients and their partners must use an effective method of contraception associated with a low failure rate prior to study entry, for the duration of study participation, and for at least 6 months after the last dose of study drug.
- Be able to comply with the requirements of the entire study.
- Provide written informed consent prior to any study related procedure. (In the event that the patient is re-screened for study participation or a protocol amendment alters the care of an ongoing patient, a new informed consent form must be signed.)
Exclusion Criteria:
Patients meeting any one of these exclusion criteria will be prohibited from participating in this study.
- Received any previous treatment for AML
- Diagnosed with APL-M3 or CBF-AML
- Require concomitant chemotherapy, radiation therapy, or immunotherapy. Hydroxyurea is allowed up to the evening before starting (but not within 12 hours) of starting Induction therapy.
- Received >200 mg/m2 equivalents of daunorubicin
- Have a peripheral blast count of >30,000/mm3 (may use hydroxyurea as in #3 above)
- Have active central nervous system (CNS) leukemia
- Have evidence of uncontrolled disseminated intravascular coagulation
- Have an active, uncontrolled infection
- Have other life-threatening illness
- Have other active malignancies or diagnosed with other malignancies within the last 6 months, except nonmelanoma skin cancer or cervical intraepithelial neoplasia
- Have mental deficits and/or psychiatric history that may compromise the ability to give written informed consent or to comply with the study protocol.
- Are pregnant and/or nursing
Sites / Locations
- Sidney Kimmel Cancer Center at Johns Hopkins
- Columbia University
- University of North Carolina
Arms of the Study
Arm 1
Experimental
Alvocidib and Cytarabine/Daunorubicin
The starting dose of alvocidib will be 20 mg/m2 as a 30-minute intravenous (IV) bolus followed by 30 mg/m2 over 4 hours as an IV infusion administered daily on Days 1-3 of Induction. Patients will have a one day drug holiday (Day 4) before initiation of the 7+3 regimen. Beginning on Day 5, cytarabine will be administered as a 100 mg/m2/day continuous IV infusion for seven consecutive days (Days 5-11) plus daunorubicin administered at a dosage of 60 mg/m2 IV on Days 5-7.