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

NCT02335814 | Terminated Phase 1

• 1 other identifier: FLX925-01
• Study Type: interventional
• Target: 51
• Locations: 1 country
• Sites: 12

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.

Conditions

Acute Myeloid Leukemia

Outcome Measures

Primary Outcomes (3)

• Safety: Incidence of adverse events

  30 Months

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

  12 Months

• Assess the antitumor activity of FLX925 when administered at the RP2D dose

  30 Months

Secondary Outcomes (4)

• 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)

  30 Months

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

  30 Months

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

  30 Months

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

  30 Months

Study Arms (1)

FLX925

EXPERIMENTAL

Drug: FLX925

Interventions

FLX925 DRUG

FLX925

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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;

You may not qualify if:

• 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;
• 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;

Sponsors & Collaborators

• RAPT Therapeutics, Inc.: lead

Study Sites (12)

Mayo Clinic

Scottsdale, Arizona, 85259, United States

Location

University of Colorado Cancer Center

Aurora, Colorado, 80045, United States

Location

Mayo Clinic Cancer Center

Jacksonville, Florida, 32224, United States

Location

Northwestern University, Robert H. Lurie Comprehensive Cancer Center

Chicago, Illinois, 60611, United States

Location

University of Michigan

Ann Arbor, Michigan, 48109, United States

Location

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

Duke Cancer Center

Durham, North Carolina, 27710, United States

Location

University of Pennsylvania, Abramson Cancer Center

Philadelphia, Pennsylvania, 19104, United States

Location

MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Huntsman Cancer Institute

Salt Lake City, Utah, 84112, United States

Location

University of Washington/Seattle Cancer Care Alliance

Seattle, Washington, 98109, United States

Location

MeSH Terms

Conditions

Leukemia, Myeloid, Acute

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Study Officials

• Jorge E Cortes, MD

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 5, 2015
• First Posted: January 12, 2015
• Study Start: April 8, 2015
• Primary Completion: May 3, 2017
• Study Completion: May 3, 2017
• Last Updated: February 9, 2018

Record last verified: 2018-02

Locations

US (12)