CHIP-AML22/Quizartinib: Quizartinib + Chemotherapy in Newly Diagnosed Pediatric FLT3-ITD+ and NPM1wt AML Patients
- Conditions
- Acute Myeloid Leukemia in Children
- Interventions
- Registration Number
- NCT06262438
- Lead Sponsor
- Princess Maxima Center for Pediatric Oncology
- Brief Summary
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.
- Detailed Description
The CHIP-AML22/Quizartinib study is a single-arm, multinational, multicenter, open-label phase II study, with a safety run-in, aiming to assess the safety, efficacy, pharmacokinetics and pharmacodynamics of quizartinib, a FLT3-inhibitor, as IMP added to standard of care chemotherapy in newly diagnosed FLT3-ITD positive and NPM1 wild-type AML pediatric patients.
This study is a linked trial to the CHIP-AML22/Master protocol. Patients will start in the CHIP-AML22/Master study and if they are FLT3-ITD positive and NPM1 wild-type, can be enrolled in the CHIP-AML22/Quizartinib study.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 60
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Quizartinib Daunorubicin 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 Quizartinib allo-SCT 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 Quizartinib Etoposide 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 Quizartinib Mitoxantrone 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 Quizartinib Dexrazoxane 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 Quizartinib Cytarabine 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 Quizartinib Methotrexate 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 Quizartinib Fludarabine 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 Quizartinib Quizartinib 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
- Primary Outcome Measures
Name Time Method 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 2Primary 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.
- Secondary Outcome Measures
Name Time Method Secondary objectives (efficacy_6) 3 years Duration of response
Pharmacokinetics (PK_2) 1.5 years Population PK analysis to estimate Cmax for quizartinib and AC886
Secondary objectives (efficacy_1) 2 induction courses (maximum of 56+/-2 days per course) Morphological overall response rate (ORR)
Pharmacokinetics (PK_1) 1.5 years Population PK analysis to estimate AUC (tau) for quizartinib and AC886
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_8) 1 year Number and percentage of patients actually being treated with hematopoietic stem cell transplantation (HSCT)
Secondary objectives (safety) - Adverse Events, Laboratory Abnormalities and cumulative incidence of non-relapse mortality 1.5 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.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 formulations 1.5 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 (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_7) 3 years Cumulative incidence of relapse (CIR)
Secondary objectives (efficacy_9) 1.5 years Number of patients starting and completing continuation treatment post-HSCT.
Trial Locations
- Locations (1)
Princess Máxima Center for pediatric oncology
🇳🇱Utrecht, Netherlands