GILTERITINIB for Acute myeloid leukemia

Inclusion criteria

• {"criterion_text":"- Signed informed consent\n- Newly diagnosed AML according to WHO 2022 criteria or AML according to ICC 2022 criteria with a minimum bone marrow (BM) blast count of ≥20%, excluding Acute Promyelocytic Leukemia (APL)\n- FLT3 mutation at initial diagnosis (ID): FLT3-internal tandem duplication (ITD) or FLT3-tyrosine kinase domain (TKD) determined by local lab\n- Age ≥18 years\n- Ineligibility for standard induction therapy as defined by: (a) ≥75 years of age OR (b) ≥18 to 74 years of age with at least one of the following comorbidities: •\tEastern Cooperative Oncology Group (ECOG) Performance Sta-tus 2 or 3; •\tCardiac history of congestive heart failure requiring treatment or Ejection Fraction ≤50% or chronic stable angina; •\tDiffusing capacity of the lungs for carbon monoxide ≤65% or Forced Expiratory Volume in 1 Second ≤65%; •\tCreatinine clearance ≥30 mL/min to <45 mL/min; •\tModerate hepatic impairment with total bilirubin >1.5 to ≤3.0 × upper limit of normal; •\tAny other comorbidity that the physician judges to be incompati-ble with intensive chemotherapy must be reviewed and approved by the coordinating investigator before study enrollment\n- Pre-treatment with approved combination of VEN+AZA (one cycle only) and availability of the results of BM assessment of this VEN+AZA precycle\n- Male subjects must agree to refrain from unprotected sex and sperm donation from time point of signing the informed consent until 4 months after the last dose of study drug\n- Women of childbearing potential must have a negative serum or urine pregnancy test performed within 3 days before first dose of study drug"}

Exclusion criteria

• {"criterion_text":"- Relapsed or primary refractory AML\n- Addictions or other illnesses that do not allow the person concerned to assess the nature and extent of the clinical trial and its possible consequences\n- Pregnant or breastfeeding women\n- Previous treatment for AML (except for hydroxyurea and/or one cycle of approved combination treatment with VEN+AZA according to standard of care (SOC))\n- Women of childbearing potential, except women who meet the following criteria: post-menopausal (12 months natural amenorrhea or 6 months amenorrhea with serum follicle-stimulating hormone >40 U/mL); postoperative (6 weeks after bilateral ovariectomy with or without hysterectomy); regular and correct use of a contraceptive method with a Pearl Index <1% per year (i.e., combined estrogen and progesterone containing or progesterone-only hormonal contraception associated with inhibition of ovulation, an intrauterine device, or an intrauterine hormone-releasing system) in combination with a barrier method since GILT as well as VEN may reduce the effectiveness of hormonal contraceptives; sexual abstinence; vasectomy of the partner\n- Indications that the subject is unlikely to adhere to the protocol (e.g., lack of compliance)\n- Previous treatment with GILT\n- Known active involvement of central nervous system with AML\n- Human immunodeficiency virus (HIV) infection and/or positive HIV serology due to potential drug-drug interactions between antiretroviral medications and VEN\n- History of active or chronic infectious hepatitis B or C unless serology demonstrates clearance of infection, i.e., polymerase chain reaction (PCR) undetectable viral load for hepatitis\n- Malabsorption syndrome or other condition that precludes enteral route of administration\n- Mean of triplicate corrected QT interval by Fredericia (QTcF) >450 ms at screening\n- Inability to swallow oral medication\n- History of other malignancies within 2 years prior to study entry, with the exception of adequately treated in situ carcinoma of the cervix uteri or carcinoma in situ of breast; basal cell carcinoma of the skin or localized squamous cell carcinoma of the skin; previous malignancy confined and surgically resected; incidental histologic finding of prostate cancer\n- Persons dependent on the sponsor, investigator or medical staff of the trial team\n- Long QT Syndrome at screening\n- Uncontrolled hypokalemia and hypomagnesemia (defined as values below lower limit of normal)\n- Treatment with concomitant strong cytochrome P450, family 3, subfamily A (CYP3A) inducers or St. John's wort\n- Treatment with concomitant strong P-glycoprotein (P-gp) inhibitors or inducers of P-gp with the exception of drugs that are considered absolutely essential for the care of the subject\n- Hypersensitivity known from medical history to GILT or VEN or AZA or their ingredients or to drugs with a similar chemical structure\n- Live-virus vaccines given within 28 d prior initiation of study treatment\n- Simultaneous participation in another interventional clinical trial (including within the last 4 weeks before planned treatment start within the trial) and the use of any other investigational medicinal product within five times the half-life of the investigational medicinal product or of relevant metabolites prior to screening"}

Primary endpoints

• {"endpoint_text":"- Ratio of dose delivered/dose planned over the 12-cycle treatment period as evaluated at 12 months. This endpoint reflects both treatment efficacy (patients live longer event-free), and safety (less dose reductions, less omitted doses)","definition_or_measurement_approach":"Ratio of dose delivered/dose planned over the 12-cycle treatment period as evaluated at 12 months; described in text as reflecting both treatment efficacy (patients live longer event-free) and safety (less dose reductions, less omitted doses)."}

Secondary endpoints

• {"endpoint_text":"- Ratio of dose delivered/dose planned over 2 cycles evaluated after 75 days","definition_or_measurement_approach":"Evaluated after 75 days (over 2 cycles) as stated."}
• {"endpoint_text":"- Complete hematologic remission/complete remission with partial hematologic recovery (CR/CRh), DOR, RFS, OS, CIR","definition_or_measurement_approach":""}
• {"endpoint_text":"- Depth of response by MRD","definition_or_measurement_approach":""}
• {"endpoint_text":"- Tolerability (Adverse events)","definition_or_measurement_approach":""}
• {"endpoint_text":"- Duration of cytopenias, transfusion dependence","definition_or_measurement_approach":""}

Germany

Earliest CTIS Part Ii Submission Date

09-08-2024

Latest Decision Or Authorization Date

11-05-2026

Processing Time Days

640

Number Of Sites

13

Number Of Participants

60

Primary sponsor

Full Name

Technische Universitat Dresden

Organisation Type

Educational Institution

Country Of Registered Address

Germany

Third parties

• {"country":"","full_name":"Astellas Pharma Europe Ltd.","duties_or_roles":"Monetary support","organisation_type":""}