Ph I Study of Alvocidib and Cytarabine / Daunorubicin (7+3) in Patients With Newly Diagnosed Acute Myeloid Leukemia (AML).
The purpose of this Phase I study is to determine the safety and tolerability including the maximum dose (MTD) and dose-limiting toxicities (DLTs) of alvocidib when administered over a range of doses on Days 1-3 followed by cytarabine / daunorubicin (7+3) on Days 5-11 in adults with newly diagnosed and previously untreated AML
- 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 during and for 6 months after completion of study therapy (see Section 4.5.3).
- 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.)
- 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 >100 mg/m2 equivalents of daunorubicin (see Appendix G for conversion table)
- 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
Locations & Contacts
Name Not Available
Contact: Sarah Jeanne Leach
Contact: Jian Zhang
Trial Objectives and Outline
Primary Objective: • To determine the safety and tolerability including the maximum tolerated dose (MTD) and dose-limiting toxicities (DLTs) of alvocidib when administered over a range of doses on Days 1-3 followed by cytarabine/daunorubicin (7+3) on Days 5-11 in adults with newly diagnosed and previously untreated AML Secondary Objectives: - To observe patients for any evidence of antileukemic activity of alvocidib plus 7+3 using the 2017 ELN response criteria - To study the correlation between the benefit from alvocidib and sequential 7+3 therapy and BH3 profiling for MCL-1 dependency and other potential biomarkers including, but not limited to, NOXA, MS1, or TMS1 using bone marrow aspirates and peripheral blood samples - To establish the Recommended Phase 2 Dose (RP2D) for future studies with alvocidib in combination with 7+3 Exploratory Objective: • To assess levels of minimal residual disease (MRD) using standardized techniques
Trial Phase & Type
Tolero Pharmaceuticals, Inc.
Secondary IDs NCI-2018-00036
Clinicaltrials.gov ID NCT03298984