Title

FLYSYN in MRD Positive AML
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
  • Phase

    Phase 1/Phase 2
  • Study Type

    Interventional
  • Status

    Completed No Results Posted
  • Intervention/Treatment

    flysyn ...
  • Study Participants

    31
This is a first in human, prospective, multicentric, 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.
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, FLYSYN 15 mg/m² BSA day 15, FLYSYN 15 mg/m² BSA day 29
Study Started
Feb 07
2017
Primary Completion
Sep 27
2021
Study Completion
Sep 27
2021
Last Update
Sep 28
2021

Biological FLYSYN

Cohort 1: Patient 1-3: FLYSYN 0.5 mg/m² BSA* day 1 Cohort 2: Patient 4-6: FLYSYN 0.5 mg/m² BSA day 1 FLYSYN 1.0 mg/m² BSA day 2 Cohort 3: Patient 7-9: FLYSYN 0.5 mg/m² BSA day 1, FLYSYN 4.5 mg/m² BSA day 2 Cohort 4: Patient 10-12 and 13-18: FLYSYN 0.5 mg/m² BSA day 1, FLYSYN 14.5 mg/m² BSA day 2 Cohort 5: Patient 19-21: FLYSYN 0.5 mg/m² BSA day 1, FLYSYN 44.5 mg/m² BSA day 2 Cohort 6: Patient 22-24 and 25-31: FLYSYN 0.5 mg/m² BSA day 1, FLYSYN 14.5 mg/m² BSA day 2, FLYSYN 15 mg/m² BSA day 15, FLYSYN 15 mg/m² BSA day 29 * The maximum upper limit for calculation of antibody dose is fixed at a body surface of 2.0 m², even if the calculated body surface exceeds this. In this study DLT are defined as the following treatment-related adverse events or laboratory abnormalities, graded according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 4.03.

Experimental: FLYSYN Experimental

IV infusion over a 3-hr duration

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 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 (determined by NGS and NPM1 RT-PCR, where applicable) 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/MDS, unless the subject has been free of the disease for ≥ 2 years. 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 T1
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)
No Results Posted