Teicoplanin as Infection Prophylaxis in Pediatric Acute Myeloid Leukemia (Pro-Teico study)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Prinses Maxima Centrum voor Kinderoncologie B.V.

Participant type

Pediatric, Patients

Age range

0-17 years, 18-64 years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

20 May 2020 → ongoing

Decision date (initial)

2024-07-22

Transition trial

Yes

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

External identifiers

EU CT number

2023-506546-23-00

EudraCT number

2020-000508-13

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacokinetic, Efficacy, Safety, Prophylaxis

For safety run in phase: To assess the safety of i.v. teicoplanin prophylaxis three times per week with a two to three days interval in children with newly-diagnosed AML.

For randomized control phase: To evaluate whether i.v. teicoplanin prophylaxis in children with newly-diagnosed AML decreases the occurrence of culture-proven BSIs with VGS during treatment.

Secondary objectives 12

1. Saftey run in phase: To (preliminary) characterize the PK parameters of teicoplanin in children with newly-diagnosed AML.
2. To evaluate whether i.v. teicoplanin prophylaxis in children with newly-diagnosed AML decreases the occurrence of any culture-proven bacterial BSI during treatment
3. To assess the impact of teicoplanin prophylaxis on the number of intensive care admissions during initial AML treatment
4. To assess the frequency of infectious-related morbidity and infection-related mortality
5. To evaluate whether i.v. teicoplanin prophylaxis affects neutrophil recovery time
6. To assess the development of teicoplanin-related bacterial resistance in (routine) surveillance cultures and breakthrough infections
7. To assess the safety and adverse events (AEs) of teicoplanin prophylaxis, with special interest regarding nephrotoxicity, ototoxicity, allergic, infusion-related or anaphylactic reactions to teicoplanin administration, sepsis with teicoplanin-resistant organisms, and the occurrence of teicoplanin-resistant organisms in routine surveillance cultures
8. To study if there is a confounding effect of the use of other antibiotics (e.g., fluoroquinolones) on the occurrence of culture-proven (VGS) bacterial BSIs during treatment
9. To assess PK parameters and construct a population PK model of teicoplanin in children with AML
10. To study the potential effect of co-variables on teicoplanin clearance in children treated for AML, including renal function, age, and co-medication
11. To study associations between serum levels of teicoplanin and the occurrence of culture-proven (VGS) bacterial BSIs during treatment
12. To describe the durability of response and long-term follow-up, the cumulative incidence of relapse (CIR) after achieving response, event-free survival (EFS) and overall survival (OS).

Conditions and MedDRA coding

Acute myeloid leukemia

Study design 1 period

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 4

1. Newly diagnosed with AML
2. Being registered and starting treatment according to the NOPHO-DBH AML 2012 study protocol, or a consecutive protocol
3. Age 0-19 years
4. Written informed consent by the patient and/or legal guardians (whatever applicable according to the patients’ age)

Exclusion criteria 10

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

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 3

1. For safety run in phase: The number of DLTs observed
2. For the randomized controlled phase: The (first) occurrence of a culture-proven BSI with VGS during initial AML treatment
3. For the randomized controlled phase: Date(s) of BSI(s) with VGS.

Secondary endpoints 20

1. 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)
2. The number of BSIs with culture-proven bacteria; o Results of all positive blood cultures
3. Infection-related (pediatric) intensive care admissions; o Days at the intensive care
4. The number of episodes/admissions with (neutropenic) fever; o Days with fever (with or without neutropenia) o Days with FN o Days with neutropenia
5. Infection-free survival time, i.e., time from diagnosis to the first culture-proven BSI
6. Infection-related mortality
7. Number of days until neutrophil recovery (ANC of ≥0.5 x109/L following the nadir)
8. Resistance patterns of pathogenic isolates from blood cultures
9. Incidence of resistant bacteria in rectal swabs: o VRE
10. 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)
11. 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
12. Serious adverse events (SAEs)
13. Use of (other) antibiotics, antifungals and antivirals
14. 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)
15. Serum creatinine levels
16. Serum levels of teicoplanin
17. Duration of response (time between achieving complete remission (CR) after starting study treatment and documented relapse or death);
18. CIR (Cumulative incidence of relapse)
19. EFS (Event-free survival)
20. OS (Overall survival)

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 4

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Prinses Maxima Centrum voor Kinderoncologie B.V.

Sponsor organisation

Prinses Maxima Centrum voor Kinderoncologie B.V.

Address

Heidelberglaan 25

City

Utrecht

Postcode

3584 CS

Country

Netherlands

Scientific contact point

Organisation

Prinses Maxima Centrum voor Kinderoncologie B.V.

Contact name

Gertjan Kaspers

Public contact point

Organisation

Prinses Maxima Centrum voor Kinderoncologie B.V.

Contact name

Secretary TDC

Third parties 1

Locations

4 EU/EEA countries · 15 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 28 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

4 submissions — initial application plus substantial / non-substantial modifications