Teicoplanin for Acute myeloid leukemia

Inclusion criteria

• {"criterion_text":"- Newly diagnosed with AML\n- Being registered and starting treatment according to the NOPHO-DBH AML 2012 study protocol, or a consecutive protocol\n- Age 0-19 years\n- Written informed consent by the patient and/or legal guardians (whatever applicable according to the patients’ age)"}

Exclusion criteria

• {"criterion_text":"- Acute promyelocytic leukemia\n- Patients that are participating in another clinical study with an IMP, that interferes with the study objectives\n- Secondary AML\n- Down Syndrome\n- Preexisting primary immunodeficiency\n- Patients who receive regular antibiotic prophylaxis against Gram-positive bacteria for other conditions than leukemia-related\n- Patients with a history of an anaphylactic reaction (CTCAE1 grade ≥3) to teicoplanin and/or vancomycin\n- Patients with an eGFR49 of <30 ml/min/1.73m2 at the start of the study\n- Patients with a history of severe impaired hearing (CTCAE1 grade ≥3)\n- Pregnant or breast-feeding patients"}

Primary endpoints

• {"endpoint_text":"- For safety run in phase: The number of DLTs observed","definition_or_measurement_approach":"Count of dose-limiting toxicities (DLTs) observed during the safety run-in phase."}
• {"endpoint_text":"- For the randomized controlled phase: The (first) occurrence of a culture-proven BSI with VGS during initial AML treatment","definition_or_measurement_approach":"Documented first occurrence of bloodstream infection (BSI) confirmed by microbiological culture yielding viridans group streptococci (VGS) during initial AML treatment."}
• {"endpoint_text":"- For the randomized controlled phase: Date(s) of BSI(s) with VGS.","definition_or_measurement_approach":"Recording of calendar date(s) when culture-proven VGS BSI(s) were diagnosed (based on positive blood culture dates)."}

Secondary endpoints

• {"endpoint_text":"- Safety run in phase: PK parameters of teicoplanin, e.g., o Css,max o Css,min o Tss,max o Area under the curve o Clearance (inter-compartmental, total, renal fraction) o Volume of distribution (central and peripheral)","definition_or_measurement_approach":"Pharmacokinetic sampling and analysis to estimate parameters such as Css,max, Css,min, Tss,max, AUC, clearance, and volumes of distribution."}
• {"endpoint_text":"- The number of BSIs with culture-proven bacteria; o Results of all positive blood cultures","definition_or_measurement_approach":"Count of bloodstream infections with culture-proven bacterial pathogens and recording of results from all positive blood cultures."}
• {"endpoint_text":"- Infection-related (pediatric) intensive care admissions; o Days at the intensive care","definition_or_measurement_approach":"Number of ICU admissions related to infection and total ICU days recorded from hospital records."}
• {"endpoint_text":"- The number of episodes/admissions with (neutropenic) fever; o Days with fever (with or without neutropenia) o Days with FN o\tDays with neutropenia","definition_or_measurement_approach":"Counting episodes/admissions with fever and neutropenic fever (FN); recording days with fever, days with FN and days with neutropenia per patient."}
• {"endpoint_text":"- Infection-free survival time, i.e., time from diagnosis to the first culture-proven BSI","definition_or_measurement_approach":"Time-to-event analysis measuring days from AML diagnosis to first culture-proven BSI."}
• {"endpoint_text":"- Infection-related mortality","definition_or_measurement_approach":"Deaths attributable to infection recorded and adjudicated as infection-related mortality."}
• {"endpoint_text":"- Number of days until neutrophil recovery (ANC of ≥0.5 x109/L following the nadir)","definition_or_measurement_approach":"Days from nadir to recovery defined as ANC ≥0.5 x10^9/L."}
• {"endpoint_text":"- Resistance patterns of pathogenic isolates from blood cultures","definition_or_measurement_approach":"Microbiological susceptibility testing of pathogenic blood isolates to determine resistance patterns."}
• {"endpoint_text":"- Incidence of resistant bacteria in rectal swabs: o VRE","definition_or_measurement_approach":"Routine rectal swab surveillance and culture to detect VRE carriage; incidence calculated."}
• {"endpoint_text":"- Incidence of resistant bacteria in (routine) surveillance cultures; throat and rectal swabs, e.g.,; o Gram-negative staphylococci o Hemolytic streptococci o Staphylococcus aureus o Fungi o Yeasts o Haemophilus influenza (only throat swab) o Pneumococci (only throat swab)","definition_or_measurement_approach":"Surveillance cultures (throat and rectal swabs) processed to detect and record incidence of listed organisms and resistant strains."}
• {"endpoint_text":"- AEs of special interest, i.e.; o Grade 3 or 4 increases in serum creatinine o Grade 3 or 4 hearing impairment o Grade 3 or 4 allergic or infusion-related reaction to teicoplanin administration o Grade 3 or 4 anaphylactic reaction to teicoplanin administration o Grade 3 or 4 sepsis with teicoplanin-resistant organisms o The occurrence of teicoplanin-resistant organisms in routine surveillance cultures","definition_or_measurement_approach":"Adverse events graded per CTCAE; specific monitoring of serum creatinine, audiology, allergic/infusion and anaphylactic reactions, and surveillance cultures for teicoplanin-resistant organisms."}
• {"endpoint_text":"- Serious adverse events (SAEs)","definition_or_measurement_approach":"Recording and reporting of SAEs per regulatory requirements."}
• {"endpoint_text":"- Use of (other) antibiotics, antifungals and antivirals","definition_or_measurement_approach":"Recording concomitant and rescue antimicrobial treatments during study period."}
• {"endpoint_text":"- PK parameters of teicoplanin, e.g.,; o Css,max o Css,min o Tss,max o Area under the curve o Clearance (inter-compartmental, total, renal fraction) o Volume of distribution (central and peripheral)","definition_or_measurement_approach":"PK sampling and population PK modelling to estimate listed PK parameters."}
• {"endpoint_text":"- Serum creatinine levels","definition_or_measurement_approach":"Serial measurement of serum creatinine to assess renal function and AEs."}
• {"endpoint_text":"- Serum levels of teicoplanin","definition_or_measurement_approach":"Measurement of teicoplanin trough/peak serum concentrations."}
• {"endpoint_text":"- Duration of response (time between achieving complete remission (CR) after starting study treatment and documented relapse or death);","definition_or_measurement_approach":"Time from achieving CR to documented relapse or death; time-to-event analysis."}
• {"endpoint_text":"- CIR (Cumulative incidence of relapse)","definition_or_measurement_approach":"Cumulative incidence function estimating relapse over time."}
• {"endpoint_text":"- EFS (Event-free survival)","definition_or_measurement_approach":"Event-free survival measured from diagnosis/start to predefined events (relapse, death, etc.)."}
• {"endpoint_text":"- OS (Overall survival)","definition_or_measurement_approach":"Overall survival measured from diagnosis/start to death from any cause."}

Netherlands

Earliest CTIS Part Ii Submission Date

08-07-2024

Latest Decision Or Authorization Date

21-08-2025

Processing Time Days

409

Number Of Sites

1

Number Of Participants

50

Denmark

Earliest CTIS Part Ii Submission Date

08-07-2024

Latest Decision Or Authorization Date

22-08-2025

Processing Time Days

410

Number Of Sites

2

Number Of Participants

20

Spain

Earliest CTIS Part Ii Submission Date

08-07-2024

Latest Decision Or Authorization Date

31-10-2025

Processing Time Days

480

Number Of Sites

10

Number Of Participants

40

Belgium

Earliest CTIS Part Ii Submission Date

08-07-2024

Latest Decision Or Authorization Date

20-11-2025

Processing Time Days

500

Number Of Sites

2

Number Of Participants

18

Primary sponsor

Full Name

Prinses Maxima Centrum voor Kinderoncologie B.V.

Organisation Type

Hospital/Clinic/Other health care facility

Country Of Registered Address

Netherlands

Third parties

• {"country":"Denmark","full_name":"GCP-enheden ved Aalborg og Aarhus Universitetshospitaler","duties_or_roles":"sponsorDuties code: 1","organisation_type":"Health care"}