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 LeukemiaRefractory AMLRelapsed AMLAMLNewly diagnosed high-risk AMLLeukemiaLeukemia, MyeloidLeukemia, Myeloid, AcuteCytarabineMitoxantroneAlvocidib
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 UCSDaccepting new patients
San DiegoCalifornia92093-2024United States
- University of California Los Angeles (UCLA)accepting new patients
Los AngelesCalifornia90095United States
- accepting new patients
- Start Date
- Completion Date
- Tolero Pharmaceuticals, Inc.
- Phase 2
- Study Type
- Last Updated
Please contact me about this study
We will not share your information with anyone other than the team in charge of this study. Submitting your contact information does not obligate you to participate in research.
The study team should get back to you in a few business days.