AzTrials
AzTrials

Acute Myeloid LeukemiaPhase 1/2FLYSYN-101NCT02789254

FLYSYN in MRD Positive AML

A Phase 1/2 study testing FLYSYN in people with Acute Myeloid Leukemia, run by Synimmune GmbH at 5 sites in Germany.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Acute Myeloid Leukemia
What is being tested?
FLYSYN
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
31 participants
Where
5 sitesGermany
Study dates
7 Feb 2017to 27 Sep 2021
Phase
Phase 1/2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
Show all 17Show fewer
  • 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.

Who cannot join

  • 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
Show all 15Show fewer
  • 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)

Trial locations and contacts

5 sites in 1 country.

5 sites in 1 country

Germany5 sites

  • Hannover Medical School

    Hanover, Lower Saxony, 30625

  • University Hospital of Heidelberg

    Heidelberg, 69120

  • University of Leipzig Medical Center

    Leipzig, 04103

  • University Hospital Tuebingen

    Tübingen, Baden-Wurttemberg, 72076

  • University Hospital Ulm

    Ulm, Baden-Wurttemberg, 89081

Other trials in Germany

About this study

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

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.

Read the 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

Being tested
FLYSYN
Keywords
acute myeloid leukemia, Fms-like receptor tyrosine kinase (FLT3), stem cell transplantation, complete remission, CD135, antibodies, Leukemia, AML, Fc-optimized
Medical subject headings
Leukemia, Myeloid, Acute, Pathologic Complete Response, Leukemia

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • FLYSYNBiological

    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.
Study groups in NCT02789254
Study groupRoleWhat they receive
Experimental: FLYSYNExperimentalIV infusion over a 3-hr duration
Receives: Biological: FLYSYN

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Incidence and severity of adverse events (AE) (CTCAE V 4.03)

    Measured: until 28 days (i.e. Visit7, day 29) after last dosing

Secondary outcomes (8)

  1. Incidence and severity of adverse events (AE) (CTCAE V 4.03)

    Measured: until 180 days (i.e.Visit 11, day 180) after last dosing

  2. Pharmacokinetics and pharmacodynamics

    Measured: Visit 1 to 13

  3. 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

    Measured: BSL; Visits 5-7;9-13

  4. Absolute and percent change from baseline in measurements of B, T, and NK cell populations and activation

    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.

    Measured: Visits 1;3;4;5;9

  5. Change in cytokines from baseline

    Measured: Visits 1-3;5 +6

  6. Overall response rate, defined as MRD negativity or reduction of at least one log step,

    Measured: BSL; Visits1;4-13

  7. Duration of response, time to MRD progression (log step), time to relapse

    Measured: BSL; Visits1;4-13

  8. Absolute change from baseline in overall quality of life scores (EORTC QLQ C-30)

    Measured: Visit 1, Visit 6,Visit 9,Visit 10, Visit 11, Visit 12, Visit 13

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted2 Jun 2016 (estimated)
  2. Study start7 Feb 2017
  3. Primary completion27 Sep 2021
  4. Study completion27 Sep 2021

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
31 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02789254
Sponsor's protocol ID
FLYSYN_Version 6.1-17.09.2019
Acronym
FLYSYN-101
Status last verified
Dec 2023
First submitted
13 May 2016
Last updated
28 Dec 2023
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
Undecided: publication

Publications

  • Heitmann JS, Schlenk RF, Dorfel D, Kayser S, Dohner K, Heuser M, Thol F, Kapp-Schwoerer S, Labrenz J, Edelmann D, Marklin M, Vogel W, Bethge W, Walz JS, Grosse-Hovest L, Steiner M, Jung G, Salih HR. Phase I study evaluating the Fc-optimized FLT3 antibody FLYSYN in AML patients with measurable residual disease. J Hematol Oncol. 2023 Aug 17;16(1):96. doi: 10.1186/s13045-023-01490-w.

    PubMed 37587502

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing FLYSYN in people with Acute Myeloid Leukemia, run by Synimmune GmbH at 5 sites in Germany.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 17 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 28 Dec 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 5 sites in Germany. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome 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). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02789254, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Dec 2023.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Keep searching with a free account

You’ve used your 3 free searches for this session. Log in or create a free AzTrials account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in