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

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ClinicalTrials.gov Identifier: NCT02335814
Recruitment Status : Terminated (Dose escalation completed; Sponsor decision)
First Posted : January 12, 2015
Last Update Posted : February 9, 2018
Sponsor:
Information provided by (Responsible Party):
RAPT Therapeutics, Inc.

Brief 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.

Condition or disease Intervention/treatment Phase
Acute Myeloid Leukemia Drug: FLX925 Phase 1

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 51 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : April 8, 2015
Actual Primary Completion Date : May 3, 2017
Actual Study Completion Date : May 3, 2017


Arm Intervention/treatment
Experimental: FLX925 Drug: FLX925



Primary Outcome Measures :
  1. Safety: Incidence of adverse events [ Time Frame: 30 Months ]
  2. Determine the maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D) of FLX925 [ Time Frame: 12 Months ]
  3. Assess the antitumor activity of FLX925 when administered at the RP2D dose [ Time Frame: 30 Months ]

Secondary Outcome Measures :
  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) [ Time Frame: 30 Months ]
    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)

  2. Assess the effects of FLX925 on pharmacodynamic (PD) markers (changes in FLT3-ITD and FLT3-D835 allelic burden) [ Time Frame: 30 Months ]
    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

  3. Characterize tumor control according to clinical disease response assessments per Cheson criteria in subjects receiving FLX925 [ Time Frame: 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 [ Time Frame: 30 Months ]


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02335814


Locations
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United States, Arizona
Mayo Clinic
Scottsdale, Arizona, United States, 85259
United States, Colorado
University of Colorado Cancer Center
Aurora, Colorado, United States, 80045
United States, Florida
Mayo Clinic Cancer Center
Jacksonville, Florida, United States, 32224
United States, Illinois
Northwestern University, Robert H. Lurie Comprehensive Cancer Center
Chicago, Illinois, United States, 60611
United States, Michigan
University of Michigan
Ann Arbor, Michigan, United States, 48109
United States, Minnesota
Mayo Clinic
Rochester, Minnesota, United States, 55905
United States, New York
Memorial Sloan Kettering Cancer Center
New York, New York, United States, 10065
United States, North Carolina
Duke Cancer Center
Durham, North Carolina, United States, 27710
United States, Pennsylvania
University of Pennsylvania, Abramson Cancer Center
Philadelphia, Pennsylvania, United States, 19104
United States, Texas
MD Anderson Cancer Center
Houston, Texas, United States, 77030
United States, Utah
Huntsman Cancer Institute
Salt Lake City, Utah, United States, 84112
United States, Washington
University of Washington/Seattle Cancer Care Alliance
Seattle, Washington, United States, 98109
Sponsors and Collaborators
RAPT Therapeutics, Inc.
Investigators
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Principal Investigator: Jorge E Cortes, MD M.D. Anderson Cancer Center

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Responsible Party: RAPT Therapeutics, Inc.
ClinicalTrials.gov Identifier: NCT02335814     History of Changes
Other Study ID Numbers: FLX925-01
First Posted: January 12, 2015    Key Record Dates
Last Update Posted: February 9, 2018
Last Verified: February 2018

Additional relevant MeSH terms:
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Leukemia
Leukemia, Myeloid
Leukemia, Myeloid, Acute
Neoplasms by Histologic Type
Neoplasms