The purpose of this two-stage Phase 2 study is to assess the clinical response (Complete Remission) of ACM (Alvocidib/Cytarabine/Mitoxantrone) compared to CM (Cytarabine/Mitoxantrone) treatment in refractory or relapsed AML patients with demonstrated MCL-1 dependence of ≥ 40% by mitochondrial profiling in bone marrow.
Phase 2, Randomized, Biomarker-driven Study in Patients With Relapsed or Refractory Acute Myeloid Leukemia (AML) With an Exploratory Arm in Patients With Newly Diagnosed High-Risk AML and Exploratory Arms With Varying Levels of MCL-1 Dependence
In Stage 1 of the study, all eligible AML patients with demonstrated MCL-1 dependence of ≥ 40% by mitochondrial profiling in bone marrow will receive treatment with ACM.
In Stage 2, all eligible AML patients with demonstrated MCL-1 dependence of ≥ 40% by mitochondrial profiling in bone marrow will be randomized 1:1 to receive either treatment with ACM or CM.
In the NDHR exploratory arm, all eligible patients with newly diagnosed high-risk (NDHR) AML with MCL-1 dependence of ≥40% by mitochondrial profiling in bone marrow will receive treatment with ACM.
In the MCL-1 dependency exploratory arms, all eligible AML patients with demonstrated MCL-1 dependence of ≥ 30 - <40% (Arm A), 15% - <30% (Arm B), or 0 - <15% (Arm C) by mitochondrial profiling in bone marrow who are either in first relapse (within 24 months of CR) or have primary refractory AML (ie, no CR or CRi after 2 cycles of intensive anthracycline/cytarabine ± etoposide or cladribine induction) will receive treatment with ACM.
Acute Myeloid Leukemia Refractory AML Relapsed AML AML Newly diagnosed high-risk AML Leukemia Leukemia, Myeloid Leukemia, Myeloid, Acute Cytarabine Alvocidib Mitoxantrone
You can join if…
Open to people ages 18-65
- Be between the ages of ≥18 and ≤65 years
- Have an established, pathologically confirmed diagnoses of AML by World Health Organization (WHO) criteria excluding acute promyelocytic leukemia (APL-M3) with a bone marrow of >5% blasts based on histology or flow cytometry
- Be in first relapse (within 24 months of CR) or have failed induction therapy* (no CR or CRi after treatment with an intensive regimen (eg, anthracycline/cytarabine ±etoposide, gemtuzumab ozogamicin, or cladribine) or have newly diagnosed high-risk AML as defined in this protocol.
*Induction therapy may involve 1 or 2 cycles of the same regimen. Efficacy assessment of induction therapy must be >21 days from the start of the previous induction cycle.
- Demonstrate MCL-1 dependence of ≥40% by mitochondrial profiling in bone marrow, 30 -<40% for MCL-1 Dependency Exploratory Arm A, 15% - <30% (MCL-1 Dependency Exploratory Arm B), or 0 - <15% (MCL-1 Dependency Exploratory Arm C)
- 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)/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.
- . Be able to comply with the requirements of the entire study.
- . Provide written informed consent prior to any study related procedure.
You CAN'T join if...
- Received more than 2 cycles of induction therapy for AML. Investigational agents as part of front-line therapy for AML may by acceptable following discussion with the Medical Monitor. Hydroxyurea is permitted (see #5 below).
- Received any previous treatment with alvocidib or any other CDK inhibitor
- Received a hematopoietic stem cell transplant within the previous 2 months
- Have clinically significant graft versus host disease (GVHD), or GVHD requiring initiation or escalation of treatment within the last 21 days
- Require concomitant chemotherapy, radiation therapy, or immunotherapy. Hydroxyurea is allowed up to the evening before starting (but not within 12 hours) of starting treatment on either arm.
- Received >360 mg/m2 equivalents of daunorubicin
- Have a peripheral blast count of >30,000/mm3 (may use hydroxyurea as in #5 above)
- Received antileukemic therapy within the last 3 weeks (with the exception of hydroxyurea or if the patient has definite refractory disease). Refractory patients who received therapy within the last 3 weeks may be eligible with prior approval of the Medical Monitor.
- Diagnosed with acute promyelocytic leukemia (APL, M3)
- . 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
- . Have received any live vaccine within 14 days prior to first study drug administration.
- University of California San Diego UCSD accepting new patients
San Diego California 92093-2024 United States
- University of California Los Angeles (UCLA) accepting new patients
Los Angeles California 90095 United States
- accepting new patients
- Start Date
- Completion Date
- Tolero Pharmaceuticals, Inc.
- Phase 2
- Study Type
- Last Updated
Please contact me about this study
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