A Study of Patients with Relapsed or Refractory Acute Myeloid Leukemia (AML) with MCL-1 Dependence ≥ 40%

Overview

About this study

The purpose of this two-stage Phase 2 study is to assess the clinical response (Complete Remission) to FLAM compared to AM treatment in refractory or relapsed AML patients with demonstrated NOXA BH3 priming of ≥ 40% by mitochondrial profiling in bone marrow.

Participation eligibility

Participant eligibility includes age, gender, type and stage of disease, and previous treatments or health concerns. Guidelines differ from study to study, and identify who can or cannot participate. There is no guarantee that every individual who qualifies and wants to participate in a trial will be enrolled. Contact the study team to discuss study eligibility and potential participation.

Inclusion Criteria:

  • Be between the ages of ≥ 18 and ≤ 65 years old.
  • 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 (e.g., 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 ≥ 30% by mitochondrial profiling in bone marrow.

During Screening:

  • 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 at least 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. (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:

  • 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 * 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/m^2 equivalents of daunorubicin.
  • Have a peripheral blast count of > 30,000/mm^3 (may use hydroxyurea as 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.

 

Participating Mayo Clinic locations

Study statuses change often. Please contact the study team for the most up-to-date information regarding possible participation.

Mayo Clinic Location Status Contact

Jacksonville, Fla.

Mayo Clinic principal investigator

James Foran, M.D.

Closed for enrollment

Contact information:

Cancer Center Clinical Trials Referral Office

(855) 776-0015

Rochester, Minn.

Mayo Clinic principal investigator

Mark Litzow, M.D.

Closed for enrollment

Contact information:

Cancer Center Clinical Trials Referral Office

(855) 776-0015

More information

Publications

Publications are currently not available
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CLS-20438953

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