FLYSYN in MRD Positive AML

NCT02789254 | Completed Phase 1 DMC

• 1 other identifier: FLYSYN_Version 6.1-17.09.2019
• Study Type: interventional
• Target: 31
• Locations: 1 country
• Sites: 5

Brief 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.

Conditions

Acute Myeloid Leukemia

Keywords

acute myeloid leukemia; Fms-like receptor tyrosine kinase (FLT3); stem cell transplantation; complete remission; CD135; antibodies; Leukemia; AML; Fc-optimized

Outcome Measures

Primary Outcomes (1)

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

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

Secondary Outcomes (8)

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

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

• Pharmacokinetics and pharmacodynamics

  Visit 1 to 13

• 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

  BSL; Visits 5-7;9-13

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

  Visits 1;3;4;5;9

• Change in cytokines from baseline

  Visits 1-3;5 +6

Study Arms (1)

Experimental: FLYSYN

EXPERIMENTAL

IV infusion over a 3-hr duration

Biological: FLYSYN

Interventions

FLYSYN BIOLOGICAL

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

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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)

Sponsors & Collaborators

• Synimmune GmbH: lead

Study Sites (5)

University Hospital Tuebingen

Tübingen, Baden-Wurttemberg, 72076, Germany

Location

University Hospital Ulm

Ulm, Baden-Wurttemberg, 89081, Germany

Location

Hannover Medical School

Hanover, Lower Saxony, 30625, Germany

Location

University Hospital of Heidelberg

Heidelberg, 69120, Germany

Location

University of Leipzig Medical Center

Leipzig, 04103, Germany

Location

Related Publications (1)

• 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.

  PMID: 37587502 RESULT

MeSH Terms

Conditions

Leukemia, Myeloid, Acute; Pathologic Complete Response; Leukemia

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Disease Progression; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Helmut Salih, Prof. Dr.

  Department of Internal Medicine, Internal Medicine II; Oncology, haematology, clinical immunology, rheumatology and pneumology University Hospital Tuebingen

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 13, 2016
• First Posted: June 2, 2016
• Study Start: February 7, 2017
• Primary Completion: September 27, 2021
• Study Completion: September 27, 2021
• Last Updated: December 28, 2023

Record last verified: 2023-12

Locations

DE (5)