Description:
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.
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 6.1-17.09.2019
- NCT ID:
NCT02789254
Conditions
Interventions
Drug | Synonyms | Arms |
---|
FLYSYN | | Experimental: FLYSYN |
Purpose
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.
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 13-18: 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
Trial Arms
Name | Type | Description | Interventions |
---|
Experimental: FLYSYN | Experimental | IV 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 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)
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: | Active, not recruiting |
Lead Sponsor: | Synimmune GmbH |
Trial Keywords
- acute myeloid leukemia
- Fms-like receptor tyrosine kinase (FLT3)
- stem cell transplantation
- complete remission
- CD135
- antibodies
- Leukemia
- AML
- Fc-optimized
Last Updated
April 6, 2020