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

Overview

  • Study type

    Interventional
  • Study phase

    I
  • Study IDs

  • Describes the nature of a clinical study. Types include:

    • Observational study — observes people and measures outcomes without affecting results.
    • Interventional study (clinical trial) — studies new tests, treatments, drugs, surgical procedures or devices.
    • Medical records research — uses historical information collected from medical records of large groups of people to study how diseases progress and which treatments and surgeries work best.
  • During the early phases (phases 1 and 2), researchers assess safety, side effects, optimal dosages and risks/benefits. In the later phase (phase 3), researchers study whether the treatment works better than the current standard therapy. They also compare the safety of the new treatment with that of current treatments. Phase 3 trials include large numbers of people to make sure that the result is valid. There are also less common very early (phase 0) and later (phase 4) phases. Phase 0 trials are small trials that help researchers decide if a new agent should be tested in a phase 1 trial. Phase 4 trials look at long-term safety and effectiveness, after a new treatment has been approved and is on the market.

  • Site IRB
    • Scottsdale/Phoenix, Arizona: 15-004369
    • Jacksonville, Florida: 15-004369
    • Rochester, Minnesota: 15-004369
    NCT ID: NCT02335814
    Sponsor Protocol Number: FLX925-01

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. If you need assistance understanding the eligibility criteria, please contact the study team.

See eligibility criteria

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 us for help.

Mayo Clinic Location Status Contact

Scottsdale/Phoenix, Ariz.

Mayo Clinic principal investigator

Jeanne Palmer, M.D.

Closed for enrollment

Contact information:

Research Information Center

800-664-4542

Jacksonville, Fla.

Mayo Clinic principal investigator

Jeanne Palmer, M.D.

Closed for enrollment

Contact information:

Research Information Center

800-664-4542

Rochester, Minn.

Mayo Clinic principal investigator

Jeanne Palmer, M.D.

Closed for enrollment

Contact information:

Research Information Center

800-664-4542

Additional contact information

Cancer-related trials contact form

Phone: 855-776-0015 (toll-free)

International patient clinical studies questions