Clinical Trials /

FLYSYN in MRD Positive AML

NCT02789254

Description:

This is a first in human, prospective, monocentric, nonrandomized, open-label study to investigate the safety, tolerability, preliminary efficacy, pharmacokinetics, pharmacodynamics and immunogenicity of the Fc-optimized antibody FLYSYN as monotherapy in adult subjects.

Related Conditions:
  • Acute Myeloid Leukemia
Recruiting Status:

Recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: FLYSYN in MRD Positive AML
  • Official Title: First in Man Study to Evaluate the Safety, Tolerability and Preliminary Efficacy of the Fc-optimized FLT3 Antibody FLYSYN for the Treatment of Acute Myeloid Leukemia Patients With Minimal Residual Disease

Clinical Trial IDs

  • ORG STUDY ID: FLYSYN_Version 3.6-10102017
  • NCT ID: NCT02789254

Conditions

  • Acute Myeloid Leukemia

Interventions

DrugSynonymsArms
FLYSYNExperimental: FLYSYN

Purpose

This is a first in human, prospective, monocentric, nonrandomized, open-label study to investigate the safety, tolerability, preliminary efficacy, pharmacokinetics, pharmacodynamics and immunogenicity of the Fc-optimized antibody FLYSYN as monotherapy in adult subjects.

Detailed Description

      Cohort 1:

      Patient 1-3: FLYSYN 0.5 mg/m² body surface area (BSA) day 1

      Cohort 2:

      Patient 4-6: FLYSYN 0.5 mg/m² body surface area (BSA) day 1 FLYSYN 1.0 mg/m² BSA day 2

      Cohort 3:

      Patient 7-9: FLYSYN 0.5 mg/m² body surface area (BSA) day 1, FLYSYN 4.5 mg/m² BSA day 2

      Cohort 4:

      Patient 10-12 and 13-28: FLYSYN 0.5 mg/m² body surface area (BSA) day 1, FLYSYN 14.5 mg/m²
      BSA day 2
    

Trial Arms

NameTypeDescriptionInterventions
Experimental: FLYSYNExperimentalIV infusion over a 3-hr duration

    Eligibility Criteria

            Inclusion Criteria:
    
              -  Age ≥18 years at the time of voluntarily signing an IEC-approved informed consent,
                 there is no upper age limit
    
              -  Diagnosis of AML with NPM1 mutation according to WHO criteria
    
              -  Confirmed FLT3 expression on leukemic cells
    
              -  Known mutational status of FLT3 (FLT3-ITD, FLT3-TKD, FLT3 wild type)
    
              -  Hematological CR (ANC count >1.000/μL, Thrombocytes > 100.000/μL), but MRD positivity
                 after any therapy except allogeneic stem cell transplantation
    
              -  Life expectancy of > 3 months
    
              -  ECOG performance status ≤ 2
    
              -  Subject must be willing to receive transfusion of blood products
    
              -  Be willing and able to comply with the study protocol for the duration of the study
    
              -  Females of childbearing potential (FCBP) must undergo repetitive pregnancy testing
                 (serum or urine) and results must be negative
    
              -  Reliable contraception should be maintained throughout the study and for 6 months
                 after study treatment
    
              -  Unless practicing complete abstinence from heterosexual intercourse, sexually active
                 FCBP must agree to use adequate contraceptive methods
    
              -  Males (including those who have had a vasectomy) must use an effective barrier method
                 of contraception throughout the study and for 6 months after study treatment if
                 sexually active with a female of childbearing potential
    
              -  All subjects must:
    
                   -  understand that the investigational product could have a potential teratogenic
                      risk.
    
                   -  be counseled about pregnancy precautions and risks of fetal exposure.
    
                   -  be able to comply with all study-related procedures, medication use, and
                      evaluations.
    
            Exclusion Criteria:
    
            The presence of ANY of the following criteria will exclude a patient from study enrollment:
    
              -  Patients proceeding to hematopoietic stem cell transplantation (suitable candidate and
                 donor available, informed consent of patient)
    
              -  Pregnant or breast feeding females
    
              -  >5% blasts in bone marrow or extramedullary disease
    
              -  Treatment with monoclonal antibody within 3 months before treatment with FLYSYN or
                 known immunoglobulin intolerance
    
              -  Known positivity for HIV, active HBV, HCV, or Hepatitis A infection
    
              -  No consent for registration, storage and processing of the individual
                 disease-characteristics and course as well as information of the family physician
                 and/or other physicians involved in the treatment about study participation
    
              -  No consent for biobanking
    
              -  Presence of any medical/psychiatric condition or laboratory abnormalities which may
                 limit full compliance with the study, increase the risk associated with study
                 participation or study drug administration, or may interfere with the interpretation
                 of study results and, in the judgment of the investigator, would make the patient
                 inappropriate for entry into this study
    
              -  Prior history of malignancies, other than AML/myelodysplastic syndrome (MDS), unless
                 the subject has (i) been free of the disease for ≥ 2 years. (ii) Exceptions include
                 the following: Basal cell carcinoma of the skin, carcinoma in situ of the cervix,
                 carcinoma in situ of the breast, incidental histological finding of prostate cancer
                 (TNM stage of T1a or T1b)
    
              -  Patients receiving any medication listed in the Appendix IV "Prohibited Medications"
                 (within 14 days prior to the first dose of study drug)
    
              -  Uncontrolled infection, e.g. infection progressing under adequate
                 antimicrobial/antifungal/antiviral treatment
    
              -  Patients under ongoing treatment with another investigational medication or having
                 been treated with an investigational medication within 14 days of screening
    
              -  Current treatment with immunosuppressive agents
    
              -  Systemic diseases (cardiovascular, renal, hepatic, etc.) that would prevent study
                 treatment (e.g., creatinine >1.5x upper normal serum level; bilirubin, AST or AP >2.5x
                 upper normal serum level; heart failure NYHA III/IV; severe obstructive or restrictive
                 ventilation disorder)
          
    Maximum Eligible Age:N/A
    Minimum Eligible Age:18 Years
    Eligible Gender:All
    Healthy Volunteers:No

    Primary Outcome Measures

    Measure:Incidence and severity of adverse events (AE) (CTCAE V 4.03)
    Time Frame:until 28 days (i.e. Visit7, day 29) after last dosing
    Safety Issue:
    Description:

    Secondary Outcome Measures

    Measure:Incidence and severity of adverse events (AE) (CTCAE V 4.03)
    Time Frame:until 180 days (i.e.Visit 11, day 180) after last dosing
    Safety Issue:
    Description:
    Measure:Pharmacokinetics and pharmacodynamics
    Time Frame:Visit 1 to 13
    Safety Issue:
    Description:
    Measure:Immunogenicity of FLYSYN based on both absolute (number and percentage of subjects who develop HAMA/HAHA) and semi-quantitative (HAMA/HAHA titer determination of confirmed positive samples) assessments
    Time Frame:BSL; Visits 5-7;9-13
    Safety Issue:
    Description:
    Measure:Absolute and percent change from baseline in measurements of B, T, and NK cell populations and activation
    Time Frame:Visits 1;3;4;5;9
    Safety Issue:
    Description:For evaluation of the status of the immune system, B, T, and NK cells will be measured frequently throughout the study (immune status). The percentage and absolute numbers as well as the absolute and percent changes from baseline of NK cells will be evaluated (determination of absolute NK cell numbers). If feasible, CD16 and CD69 expression on NK cells will be evaluated at baseline and after antibody exposition (NK cell activation). Pending sample availability, endogenous antibody titers (e.g., tetanus titers) will be measured from remaining PK back-up samples in order to gain information about the influence of FLYSYN treatment on normal plasma cells and immunity.
    Measure:Change in cytokines from baseline
    Time Frame:Visits 1-3;5 +6
    Safety Issue:
    Description:
    Measure:Overall response rate, defined as MRD negativity or reduction of at least one log step,
    Time Frame:BSL; Visits1;4-13
    Safety Issue:
    Description:
    Measure:Duration of response, time to MRD progression (log step), time to relapse
    Time Frame:BSL; Visits1;4-13
    Safety Issue:
    Description:
    Measure:Absolute change from baseline in overall quality of life scores (EORTC QLQ C-30)
    Time Frame:Visit 1, Visit 6,Visit 9,Visit 10, Visit 11, Visit 12, Visit 13
    Safety Issue:
    Description:

    Details

    Phase:Phase 1/Phase 2
    Primary Purpose:Interventional
    Overall Status:Recruiting
    Lead Sponsor:University Hospital Tuebingen

    Trial Keywords

    • acute myeloid leukemia
    • Fms-like receptor tyrosine kinase (FLT3)
    • stem cell transplantation
    • complete remission
    • CD135
    • antibodies
    • Leukemia
    • AML
    • Fc-optimized

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