Clinical Trials /

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

NCT02335814

Description:

This first-in-human (FIH) clinical trial is a Phase 1/1b, open-label, sequential-group, dose-escalation and cohort expansion study evaluating the safety, PK, PD, and antitumor activity of FLX925 in subjects with relapsed or refractory AML.

Related Conditions:
  • Acute Myeloid Leukemia
Recruiting Status:

Terminated

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: First-in-Human Study of FLX925 in Subjects With Relapsed or Refractory Acute Myeloid Leukemia
  • Official Title: Phase 1/1b, First-in-Human, Dose-Escalation and Expansion Study of FLX925 Administered Orally to Subjects With Relapsed or Refractory Acute Myeloid Leukemia

Clinical Trial IDs

  • ORG STUDY ID: FLX925-01
  • NCT ID: NCT02335814

Conditions

  • Acute Myeloid Leukemia

Interventions

DrugSynonymsArms
FLX925FLX925

Purpose

This first-in-human (FIH) clinical trial is a Phase 1/1b, open-label, sequential-group, dose-escalation and cohort expansion study evaluating the safety, PK, PD, and antitumor activity of FLX925 in subjects with relapsed or refractory AML.

Trial Arms

NameTypeDescriptionInterventions
FLX925Experimental
  • FLX925

Eligibility Criteria

        Inclusion Criteria:

          1. Males and females age ≥ 18 yrs;

          2. Subjects with histologically confirmed relapsed or treatment refractory AML with the
             exception of subjects who are in first relapse following a remission >12 months in
             duration and are eligible for standard therapies (e.g., chemotherapy or stem cell
             transplantation).

          3. Assessment of FLT3 mutation status;

          4. Part 2 (Expansion) only: Subject must be able to be stratified into 1 of 3 cohorts:

               -  Cohort A: Subjects with a FLT3 mutation (e.g. ITD or D835) with prior FLT3
                  inhibitor treatment

               -  Cohort B: Subjects with a FLT3 mutation (e.g. ITD or D835) without prior FLT3
                  inhibitor treatment

               -  Cohort C: Subjects without a FLT3 mutation at the time of enrollment

          5. Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2;

          6. Considered by the investigator to be an appropriate candidate for a Phase 1 clinical
             study;

          7. The interval from prior treatment to time of initiation of FLX925 administration will
             be ≥ 2 weeks for cytotoxic agents and ≥ 5 half-lives for investigational/non-cytotoxic
             agents. For patients with rapidly proliferative disease, use of hydroxyurea is allowed
             if started prior to initiation of study therapy;

          8. 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]);

          9. Serum AST and ALT ≤ 3 x ULN;

         10. Serum bilirubin ≤ 2 x ULN unless due to Gilbert's syndrome or hemolysis or considered
             to be related to leukemia;

         11. Serum creatinine ≤ 1.5 mg/dL or calculated creatinine clearance (CrCl) of ≥ 60 mL/hour
             by the Cockroft-Gault equation;

         12. Normal coagulation profile as evidenced by PT and aPTT ≤ 1.5 x ULN;

         13. For women of childbearing potential, negative serum pregnancy test;

         14. 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;

         15. Ability to swallow tablets without difficulty;

         16. Willingness to comply with scheduled visits, drug administration plan,
             protocol-specified bone marrow biopsies;

         17. Written informed consent must be provided.

        Exclusion Criteria:

          1. Subjects with AML in their first relapse following a remission >12 months in duration
             who are eligible for standard therapies (e.g. chemotherapy or stem cell
             transplantation);

          2. Absolute leukemic blast count in peripheral blood >50,000/ microliter;

          3. Active, symptomatic central nervous system (CNS) leukemia;

          4. 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.

          5. Clinically significant cardiovascular disease;

          6. Significant screening electrocardiogram (ECG) abnormalities;

          7. 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;

          8. Significant active gastrointestinal disease that might impair absorption of study
             therapy;

          9. Evidence of an ongoing, uncontrolled systemic infection or an uncontrolled local
             infection requiring therapy at the time of start of study therapy

         10. Known or suspected human immunodeficiency virus (HIV) infection or patients who are
             HIV seropositive;

         11. Patients known to be positive for hepatitis B or to have active hepatitis C infection;

         12. Any evidence of ongoing graft-versus-host disease (GVHD) in subjects with prior
             progenitor cell transplantation;

         13. Pregnancy or breastfeeding;

         14. Major surgery within 4 weeks before the start of study therapy;

         15. Ongoing immunosuppressive therapy within 14 days prior to the start of study therapy;

         16. 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, or

               -  strong CYP3A4 inhibitors, or

               -  CYP3A4 or CYP2C19 or P glycoprotein (P-gp) or breast cancer resistance protein
                  (BCRP) substrates having a narrow therapeutic index;

         17. Concurrent participation in another therapeutic clinical trial;

         18. Any condition deemed by the investigator to be likely to interfere with a subject's
             ability to participate in the clinical trial.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Safety: Incidence of adverse events
Time Frame:30 Months
Safety Issue:
Description:

Secondary Outcome Measures

Measure:Evaluate the PK profile of FLX925 (maximum concentration (Cmax), time of the maximum measured concentration (Tmax), area under the concentration-time curve (AUC), and terminal elimination half-life (t1/2)
Time Frame:30 Months
Safety Issue:
Description:PK parameters include: maximum concentration (Cmax), time of the maximum measured concentration (Tmax), area under the concentration-time curve (AUC), and terminal elimination half-life (t1/2)
Measure:Assess the effects of FLX925 on pharmacodynamic (PD) markers (changes in FLT3-ITD and FLT3-D835 allelic burden)
Time Frame:30 Months
Safety Issue:
Description:PD endpoints include: changes in FLT3-ITD and FLT3-D835 allelic burden, status and changes in the cyclin/CDK/Rb pathway, and changes in immune parameters
Measure:Characterize tumor control according to clinical disease response assessments per Cheson criteria in subjects receiving FLX925
Time Frame:30 Months
Safety Issue:
Description:
Measure:Explore the relationships of PK and PD parameters to clinical drug activity as defined by clinical disease response assessments per Cheson criteria
Time Frame:30 Months
Safety Issue:
Description:

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Terminated
Lead Sponsor:FLX Bio, Inc.

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