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Éligibilité

Détails de la conception

Bras et interventions

Mesures des résultats

Sites d'essai

Source : NCT06262438

Recrutement en cours

CHIP-AML22/Quizartinib: Quizartinib + Chemotherapy in Newly Diagnosed Pediatric FLT3-ITD+ and NPM1wt AML Patients

Interventionnel

Phase 2

Princess Máxima Center for pediatric oncology

Sponsor: Princess Maxima Center for Pediatric Oncology

Dernière synchronisation : 5 août 2025
Avis - Les informations proviennent de registres publics et peuvent ne pas refléter les changements en temps réel sur le site local.

The CHIP-AML22 Master protocol has the overall aim of increasing the cure rate in newly diagnosed pediatric de novo AML patients, while avoiding unnecessary toxicity. The linked Quizartinib trial (CHIP-AML22/Quizartinib) is a phase II, single arm, open label, study on the safety, efficacy, pharmacokinetics and pharmacodynamics of quizartinib in combination with chemotherapy and as single-agent after high dose therapy in newly diagnosed pediatric AML patients with a FLT3-ITD mutation and NPM1 wild-type.

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Catégorie de traitement

Thérapie ciblée, Chimiothérapie, Autres médicaments, Autres

Mutations requises

FLT3, FLT3-ITD

Essai commencé

6 février 2024

Dernière mise à jour par le sponsor

5 août 2025

Achèvement estimé

1 juin 2028

Contact de l'étude

Nom:Renske Benedictus

E-mail:CHIP-AML22@prinsesmaximacentrum.nl

Téléphone:+31 88 972 72 72

Éligibilité

Critères d'inclusion

1. Enrollment on CHIP-AML22/Master:

Patients must be enrolled on the CHIP-AML22/Master prior to enrollment on CHIP-AML/Quizartinib linked-trial, and may have received a diagnostic work-up according to the master protocol. Induction treatment can be started as standard of care.

2. FLT3-ITD+ and wild-type NPM1:

Presence of FLT3-ITD+ and NPM1 wild type in bone marrow or peripheral blood provided by the local laboratories, as part of standard of care diagnostics. The results of FLT3-ITD testing must be obtained prior to the first dose of quizartinib (e.g., Induction course 1, Day 10).

3. Age:

Patients must be from 1 month to ≤ 18 years old at initial diagnosis

4. Performance status Karnofsky performance status score of >50% for subjects >16 years of age, and a Lansky performance status score of >50% for subjects ≤16 years of age.

5. Organ function criteria:

These criteria must be met based on the results before start of any chemotherapy (e.g., MEC) a. Adequate Renal Function Defined as:

• Calculated eGFR ≥ 50 mL/min/1.73 m2 using the Schwartz formula. b. Adequate Liver Function Defined as:

* Total or direct (conjugated) bilirubin < 1.5xULN for age (≤ 5xULN if related to leukemic involvement), AND

* Aspartate transaminase (AST) and alanine transaminase (ALT) <5xULN (<10×ULN if related to leukemic involvement)

6. Life expectancy: > 6 weeks

7. Pregnancy test:

Serum/urine pregnancy test (for all girls ≥ age of menarche) negative within 2 weeks prior to enrollment on the quizartinib linked-trial.

8. Taking quizartinib:

Patients must be able to reliably swallow or administer quizartinib by NG tube.

9. Informed consent:

Written informed consent/assent for the quizartinib linked trial from patients and/or from parents or legal guardians for minor patients, according to local law and regulations.

Critères d'exclusion

1. Patients with only extramedullary disease

2. Uncontrolled or significant cardiovascular disease, including -Diagnosed or suspected congenital long QT syndrome

-History of clinically significant ventricular arrhythmias (such as ventricular tachycardia, ventricular fibrillation, or Torsades de Pointes); any history of arrhythmia will be discussed with sponsor, the national coordinator and C.I.the prior to subject's entry into the study.

-QT interval corrected >450 ms: QTc interval corrected with Fridericia's formula (QTcF) for subjects ≥ 6 years of age at the time of enrollment.

-Left ventricular systolic dysfunction (LVSD), defined as ejection fraction (EF) below 55% during the screening for the CHIP-AML22/Master protocol.

-History of uncontrolled angina pectoris or myocardial infarction within 6 months.

-History of second (Mobitz II) or third degree heart block (subjects with pacemakers are eligible if they have nohistory of fainting or clinically relevant arrhythmias while using the pacemaker).

-Heart rate <50 beats/minute on ECG during the screening for the CHIP-AML22/Master protocol (In case,adolescents with a normal sinusoidal rhythm and no evidence of other cardiac dysfunction will be discussed with sponsor, the national coordinator and C.I. the prior to subject's entry into the study.)

-Uncontrolled hypertension (e.g., systolic blood pressure and /or diastolic blood pressure that is, on repeated measurement, at or above the 95th percentile for sex, age, and height).

* History of complete left bundle branch block.

* History of New York Heart Association Class 3 or 4 heart failure.

3. Known history of HIV or active clinically relevant liver disease (e.g., active hepatitis B or active hepatitis C)

4. Underlying GI disease that may affect absorption of study drug

5. Use of strong or moderate CYP3A inducers will be prohibited throughout the duration of the study. Strong CYP3A4 inhibitors will be allowed with a concomitant dose reduction of quizartinib with the exception during the safety run-in.

6. History of hypersensitivity to any of the study medications or their excipients.

7. Other serious illnesses or medical conditions, that will likely make it impossible to complete treatment according to protocol (e.g., patients who should not be given any of the study medications based on the SmPC)

8. Currently participating in other investigational interventional procedures, if it interferes with any endpoints of the quizartinib trial.

1. Patients with CNS3 disease

2. Using strong CYP3A4 inhibitors (If patient can stop using strong CYP3A4 inhibitors, he/she will be allowed to enroll. In such case, no washout is required for the strong CYP3A4 inhibitor)

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Détails de la conception

AllocationN/A

Modèle d'interventionSingle Group Assignment

MasquageNone (Open Label)

Nombre à inscrire60

Bras et interventions

Bras

Interventions

Type : Experimental

Description : Quizartinib will be administered for 14 days following the completion of standard of care chemotherapy for up to 3-5 cycles of induction and consolidation. After high dose chemotherapy or allo-Stem Cell Transplantation (allo-SCT), patients will receive continuation treatment with quizartinib for six 28-day courses

Interventions :

Quizartinib
Etoposide
Dexrazoxane
Mitoxantrone
Cytarabine
Methotrexate
Daunorubicin
Fludarabine
allo-SCT

Mesures des résultats

Mesures des résultats primaires

Primary objective (efficacy)2 induction courses (maximum of 56+/-2 days per course)

The percentage of patients with (Minimal Residual Disease) MRD levels <0.1% (MRD negativity) after up to 2 courses of induction chemotherapy plus quizartinib, as measured in the bone marrow using multiparameter flow cytometry (MFCM) before start of consolidation therapy, in the evaluable population for response. o Patients to be evaluated at baseline, end of cycle 1, and end of cycle 2

Primary objective (safety)2 induction courses (maximum of 56+/-2 days per course)

Incidence of Dose-Limiting Toxicities (DLTs) assessed during Induction course 1 and 2 (until day 56 of each course) for the DLTs evaluable patients.

Mesures des résultats secondaires

Secondary objectives (efficacy_1)2 induction courses (maximum of 56+/-2 days per course)

Morphological overall response rate (ORR)

Secondary objectives (efficacy_2)Multiple time points, last time point after continuation treatment (1.5 years)

MRD by multiparameter flow cytometry (MFCM)

Secondary objectives (efficacy_3)3 years

Event free survival (EFS)

Secondary objectives (efficacy_4)3 years

Overall survival (OS)

Secondary objectives (efficacy_5)3 years

Disease free survival (DFS)

Secondary objectives (efficacy_6)3 years

Duration of response

Secondary objectives (efficacy_7)3 years

Cumulative incidence of relapse (CIR)

Secondary objectives (efficacy_8)1 year

Number and percentage of patients actually being treated with hematopoietic stem cell transplantation (HSCT)

Secondary objectives (efficacy_9)1.5 years

Number of patients starting and completing continuation treatment post-HSCT.

Pharmacokinetics (PK_1)1.5 years

Population PK analysis to estimate AUC (tau) for quizartinib and AC886

Pharmacokinetics (PK_2)1.5 years

Population PK analysis to estimate Cmax for quizartinib and AC886

Pharmacokinetics (PK_3)1.5 years

Population PK analysis to estimate clearance (CL/F) for quizartinib.

Pharmacokinetics (PK_4)1.5 years

Population PK analysis to estimate volume of distribution (Vss/F) for quizartinib.

Palatability of quizartinib formulations1.5 years

Patients and/or parents or legal guardians will answer using a Hedonic scale for the taste and ability to swallow the medicine.

Secondary objectives (safety) - Adverse Events, Laboratory Abnormalities and cumulative incidence of non-relapse mortality1.5 years

Safety and tolerability of combining quizartinib with conventional treatment and quizartinib given as single-agent after HSCT. * Adverse events (AEs), as characterized by type, frequency, severity (as graded using CTCAE, v5.0). * Laboratory abnormalities (including time to recovery of ANC and PLT), electrocardiograms and changes in vital signs as characterized by type, frequency, severity and timing will be tabulated, and reported as AEs when considered clinically significant by the investigator. * The cumulative incidence of non-relapse mortality, defined as the cumulative probability of non-relapse mortality, with time calculated between start of study treatment and death due to other causes than relapsed or refractory leukemia, accounting for competing events.

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Cette étude compte 1 site d'essai

Princess Máxima Center for pediatric oncology

Utrecht, NL

Nom:Bianca Goemans, MD, PhD

Recrutement en cours

Utrecht, 3584 CS NL

Princess Máxima Center for pediatric oncology

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