First-in-Human Study of FLX925 in Subjects with Relapsed or Refractory Acute Myeloid Leukemia

Overview

About this study

This first-in-human clinical trial is a Phase 1/1b, open-label, sequential-group, dose-escalation and cohort expansion study evaluating the safety,  and antitumor activity of FLX925 in people with relapsed or refractory Acute Myeloid Leukemia.

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

  • Males and females age ≥ 18 yrs
  • Histologically confirmed Acute Myeloid Leukemia who have failed prior induction therapy or have relapsed after prior therapy
  • Assessment of FLT3 mutation status
  • Part 2 (Expansion) only: Subject must be able to be stratified into 1 of 3 cohorts
    • Cohort A: Subjects with a FLT3 mutation (ITD or D835) with prior FLT3 inhibitor treatment
    • Cohort B: Subjects with a FLT3 mutation (ITD or D835) without prior FLT3 inhibitor treatment
    • Cohort C: Subjects without a FLT3 mutation at the time of enrollment
  • Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2
  • Considered by the investigator to be an appropriate candidate for a Phase 1 clinical study
  • In the absence of rapidly progressing disease, the interval from prior treatment to time of initiation of FLX925 administration will be ≥ 2 weeks for cytotoxic agents and ≥ 5 half-lives for cytotoxic/non-cytotoxic agents.
    • For  rapidly proliferative disease, use of hydroxyurea is allowed before and up to 7 days on therapy
  • Clinically significant toxic effects of any prior antitumor therapy (except hydroxyurea) resolved to Grade ≤ 1 before the start of study therapy (bone marrow parameters Grade 1 to 4 permitted)
  • Serum AST and ALT ≤ 3 x ULN
  • Serum bilirubin ≤ 2 x ULN unless due to Gilbert's syndrome or hemolysis or considered to be related to leukemia
  • Serum creatinine ≤ 1.5 mg/dL or calculated creatinine clearance (CrCl) of ≥ 60 mL/hour by the Cockroft-Gault equation
  • Normal coagulation profile as evidenced by PT and aPTT ≤ 1.5 x ULN
  • For women of childbearing potential, negative serum pregnancy test
  • Women of childbearing potential and sexually mature males must agree to use a medically accepted method of contraception throughout the study and for 30 days following the last dose
  • Ability to swallow tablets without difficulty
  • Willingness to comply with scheduled visits, drug administration plan, protocol-specified bone marrow biopsies
  • Written informed consent must be provided

 

Exclusion Criteria

  • Subjects with AML in their first relapse following a remission >12 months in duration
  • Leukemic blast count >50,000
  • Active, symptomatic central nervous system (CNS) leukemia
  • History of another malignancy except for the following
    • Adequately treated local non-melanoma skin cancer
    • In situ cervical carcinoma
    • Adequately treated, papillary, non-invasive bladder cancer
    • Asymptomatic prostate cancer without known metastatic disease and with no requirement for therapy or requiring only hormonal therapy and with normal prostate specific antigen for ≥ 1 year prior to start of study therapy
    • Other adequately treated Stage 1 or 2 cancers currently in complete remission, or any other cancer that has been in complete remission for ≥ 2 years
  • Clinically significant cardiovascular disease
  • Significant screening electrocardiogram (ECG) abnormalities
  • Significant risk for bleeding due to active peptic ulcer disease or bleeding diathesis or requirement for systemic anticoagulation or history of significant gastrointestinal, urological, intracranial or other significant bleeding within 1 year from the start of treatment
  • Significant active gastrointestinal disease that might impair absorption of study therapy
  • Evidence of an ongoing, uncontrolled systemic infection or an uncontrolled local infection requiring therapy at the time of start of study therapy
  • Known or suspected human immunodeficiency virus (HIV) infection or patients who are HIV seropositive
  • Patients known to be positive for hepatitis B or to have active hepatitis C infection
  • Any evidence of ongoing graft-versus-host disease (GVHD) in subjects with prior progenitor cell transplantation
  • Pregnancy or breastfeeding
  • Major surgery within 4 weeks before the start of study therapy
  • Ongoing immunosuppressive therapy within 14 days prior to the start of study therapy
  • Subjects currently receiving treatment with any medications that have the following potential properties and who cannot be either discontinued or switched to a different medication
    • The potential to prolong the QT interval
    • Strong CYP3A4 inhibitors
    • CYP3A4 
    • CYP2C19 
    • P glycoprotein (P-gp) 
    • Breast cancer resistance protein (BCRP) substrates having a narrow therapeutic index
  • Concurrent participation in another therapeutic clinical trial
  • Any condition deemed by the investigator to be likely to interfere with a subject's ability to participate in the clinical trial

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

Rochester, Minn.

Mayo Clinic principal investigator

Kebede Begna, M.D.

Closed for enrollment

Contact information:

Cancer Center Clinical Trials Referral Office

855-776-0015

Scottsdale/Phoenix, Ariz.

Mayo Clinic principal investigator

Jeanne Palmer, M.D.

Closed for enrollment

Contact information:

Cancer Center Clinical Trials Referral Office

855-776-0015

Jacksonville, Fla.

Mayo Clinic principal investigator

James Foran, M.D.

Closed for enrollment

Contact information:

Cancer Center Clinical Trials Referral Office

855-776-0015

More information

Publications

Publications are currently not available

Study Results Summary

Not yet available

Supplemental Study Information

Not yet available

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CLS-20156879

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