FLYSYN in MRD Positive AML

NCT ID: NCT02789254

Last Updated: 2023-12-28

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 31 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-02-07
• Study Completion Date: 2021-09-27

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.

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

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

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Experimental: FLYSYN

IV infusion over a 3-hr duration

Group Type: EXPERIMENTAL

FLYSYN

Intervention Type: 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.

Interventions

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.

Intervention Type: BIOLOGICAL

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)

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Synimmune GmbH

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Helmut Salih, Prof. Dr.

Role: PRINCIPAL_INVESTIGATOR

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

Locations

University Hospital Tuebingen

Tübingen, Baden-Wurttemberg, Germany

University Hospital Ulm

Ulm, Baden-Wurttemberg, Germany

Hannover Medical School

Hanover, Lower Saxony, Germany

University Hospital of Heidelberg

Heidelberg, , Germany

University of Leipzig Medical Center

Leipzig, , Germany

Countries

Germany

References

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.

Reference Type: RESULT

PMID: 37587502 (View on PubMed)

Other Identifiers

FLYSYN_Version 6.1-17.09.2019

Identifier Type: -

Identifier Source: org_study_id