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Acute Myeloid LeukemiaPhase 1NCT02335814

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

A Phase 1 study testing FLX925 in people with Acute Myeloid Leukemia, run by RAPT Therapeutics, Inc., a member of the GSK plc group of companies at 12 sites in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial summary

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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Acute Myeloid Leukemia
What is being tested?
FLX925
Could I receive a placebo?
No, everyone receives an active treatment
How many people
51 participants
Where
12 sitesUnited States
Study dates
8 Apr 2015to 3 May 2017
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Males and females age ≥ 18 yrs;
  • 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).
  • 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 (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
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  • 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;
  • 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;
  • 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.

Who cannot join

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

Trial locations and contacts

12 sites in 1 country.

12 sites in 1 country

United States12 sites

  • University of Michigan

    Ann Arbor, Michigan, 48109

  • University of Colorado Cancer Center

    Aurora, Colorado, 80045

  • Northwestern University, Robert H. Lurie Comprehensive Cancer Center

    Chicago, Illinois, 60611

  • Duke Cancer Center

    Durham, North Carolina, 27710

  • MD Anderson Cancer Center

    Houston, Texas, 77030

  • Mayo Clinic Cancer Center

    Jacksonville, Florida, 32224

  • Memorial Sloan Kettering Cancer Center

    New York, New York, 10065

  • University of Pennsylvania, Abramson Cancer Center

    Philadelphia, Pennsylvania, 19104

  • Mayo Clinic

    Rochester, Minnesota, 55905

  • Huntsman Cancer Institute

    Salt Lake City, Utah, 84112

  • Mayo Clinic

    Scottsdale, Arizona, 85259

  • University of Washington/Seattle Cancer Care Alliance

    Seattle, Washington, 98109

Other trials in United States

About this study

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

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.

Being tested
FLX925
Medical subject headings
Leukemia, Myeloid, Acute

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • FLX925Drug

Study groups in NCT02335814
Study groupRoleWhat they receive
FLX925ExperimentalNot described
Receives: Drug: FLX925

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Safety: Incidence of adverse events

    Measured: 30 Months

  2. Determine the maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D) of FLX925

    Measured: 12 Months

  3. Assess the antitumor activity of FLX925 when administered at the RP2D dose

    Measured: 30 Months

Secondary outcomes (4)

  1. 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)

    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)

    Measured: 30 Months

  2. Assess the effects of FLX925 on pharmacodynamic (PD) markers (changes in FLT3-ITD and FLT3-D835 allelic burden)

    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

    Measured: 30 Months

  3. Characterize tumor control according to clinical disease response assessments per Cheson criteria in subjects receiving FLX925

    Measured: 30 Months

  4. Explore the relationships of PK and PD parameters to clinical drug activity as defined by clinical disease response assessments per Cheson criteria

    Measured: 30 Months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted12 Jan 2015 (estimated)
  2. Study start8 Apr 2015
  3. Primary completion3 May 2017
  4. Study completion3 May 2017

Why it stopped: Dose escalation completed; Sponsor decision

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
51 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02335814
Sponsor's protocol ID
FLX925-01
Status last verified
Feb 2018
First submitted
5 Jan 2015
Last updated
9 Feb 2018
Results posted
No
Data monitoring committee
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing FLX925 in people with Acute Myeloid Leukemia, run by RAPT Therapeutics, Inc., a member of the GSK plc group of companies at 12 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 20 inclusion and 21 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 9 Feb 2018. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 12 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was stopped early (reason given: Dose escalation completed; Sponsor decision). Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Safety: Incidence of adverse events (time frame: 30 Months). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02335814.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Feb 2018.

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