Trial document



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  DRKS00011887

Trial Description

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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

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Trial Acronym

FLYSYN-101

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URL of the Trial

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Brief Summary in Lay Language

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Brief Summary in Scientific Language

The purpose of this study is to characterize the safety profile and preliminary efficacy of FLYSYN as monotherapy in adult subjects with minimal residual disease (MRD) positive acute myeloid leukemia (AML), ineligible for allogeneic hematopoietic stem cell transplantation in complete remission (CR) with molecular detection of MRD.

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Do you plan to share individual participant data with other researchers?

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Description IPD sharing plan:

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Organizational Data

  •   DRKS00011887
  •   2017/03/17
  •   2016/05/13
  •   no
  •   Approved
  •   184/2016AMG1, Ethik-Kommission an der Medizinischen Fakultät der Eberhard-Karls-Universität und am Universitätsklinikum Tübingen
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Secondary IDs

  •   2016-000236-17 
  •   NCT02789254  (clinicaltrials.gov)
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Health Condition or Problem studied

  •   C92.0 -  Acute myeloblastic leukaemia [AML]
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Interventions/Observational Groups

  •   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 13-18: FLYSYN 0.5 mg/m² body surface area (BSA) day 1,
    FLYSYN 14.5 mg/m² BSA day 2

    Cohort 5:
    Patient 19-21: FLYSYN 0.5 mg/m² body surface area (BSA) day 1,
    FLYSYN 44.5 mg/m² BSA day 2

    Cohort 6:
    Patient 22-24 and 25-31: FLYSYN 0.5 mg/m² body surface area (BSA) day 1,
    FLYSYN 14.5 mg/m² BSA day 2, and
    FLYSYN 15 mg/m² BSA on day 15, and
    FLYSYN 15 mg/m² BSA on day 29
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Characteristics

  •   Interventional
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  •   Single arm study
  •   Open (masking not used)
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  •   Uncontrolled/Single arm
  •   Treatment
  •   Single (group)
  •   I-II
  •   No
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Primary Outcome

Incidence and severity of adverse events (AE) (CTCAE V4.03) until 28 days (i.e. Visit 7, day 29) after dosing for Cohorts 1 to 5 and until 35 days (i.e. Visit 9a, day 64) after last dosing for Cohort 6.

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Secondary Outcome

Incidence and severity of adverse events (AE) (CTCAE V
4.03) until 180 days (i.e. Visit 11, day 180) after dosing
• Pharmacokinetics and pharmacodynamics
• 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
• Absolute and percent change from baseline in measurements
of B, T, and NK cell populations and activation
• Absolute changes from baseline in laboratory parameters
• Change in cytokines from baseline
• Overall response rate, defined as MRD negativity or at least
one log step reduction
• Duration of response, time to MRD progression (log step), time
to relapse
• Absolute change from baseline in overall quality of life scores
(EORTC QLQ C-30)

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Countries of Recruitment

  •   Germany
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Locations of Recruitment

  • Medical Center 
  • Medical Center 
  • Medical Center 
  • Medical Center 
  • Medical Center 
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Recruitment

  •   Actual
  •   2017/02/15
  •   31
  •   Multicenter trial
  •   National
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Inclusion Criteria

  •   Both, male and female
  •   18   Years
  •   no maximum age
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Additional 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 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:
ounderstand that the investigational product could have a potential teratogenic risk.
obe counseled about pregnancy precautions and risks of fetal exposure.
obe able to comply with all study-related procedures, medication use, and evaluations.

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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, histological finding of prostate cancer of TNM stage 1.
•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)

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Addresses

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    • Synimmune GmbH
    • Mr.  Dr.  Ludger  Grosse-Hovest 
    • Alte Landstrasse 42
    • 72072  Tübingen
    • Germany
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    • Klinische Kooperationseinheit Translationale Immunologie Deutsches Konsortium für Translationale Krebsforschung (DKTK) Deutsches Krebsforschungszentrum (DKFZ) Partnerstandort TuebingenMedizinische Klinik II
    • Mr.  Professor  Helmut R.  Salih 
    • Otfried-Müller-Str. 10
    • 72076  Tübingen
    • Germany
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    • Klinische Kooperationseinheit Translationale Immunologie Deutsches Konsortium für Translationale Krebsforschung (DKTK) Deutsches Krebsforschungszentrum (DKFZ) Partnerstandort TuebingenMedizinische Klinik II
    • Mr.  Professor  Helmut R.  Salih 
    • Otfried-Müller-Str. 10
    • 72076  Tübingen
    • Germany
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Sources of Monetary or Material Support

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    • Synimmune GmbH
    • Mr.  Dr.  Ludger  Grosse-Hovest 
    • Alte Landstrasse 42
    • 72072  Tübingen
    • Germany
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Status

  •   Recruiting complete, follow-up continuing
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Trial Publications, Results and other Documents

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* This entry means the parameter is not applicable or has not been set.