FLYSYN in MRD Positive AML (FLYSYN-101)

Synimmune

Status and phase

Completed

Phase 2

Phase 1

Conditions

Acute Myeloid Leukemia

Treatments

Biological: FLYSYN

Study type

Interventional

Funder types

Industry

Identifiers

NCT02789254

FLYSYN_Version 6.1-17.09.2019

Details and patient eligibility

About

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.

Full 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 13-18: 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

Enrollment

31 patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

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)