NCT06262438

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

A Phase II, Single Arm, Open Label, Study on the Safety, Efficacy, Pharmacokinetics & Pharmacodynamics of Quizartinib + Chemotherapy and as Single-agent After High Dose Therapy in Newly Diagnosed Pediatric FLT3-ITD+ and NPM1wt AML Patients

• Status: Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 60 (estimated)
• Sponsor: Princess Maxima Center for Pediatric Oncology · Academic / Other
• Sex: All
• Age: 1 Month – 18 Years
• Healthy volunteers: Not accepted

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.

Conditions

• Acute Myeloid Leukemia in Children

Interventions

Type	Name	Description
DRUG	Quizartinib	Quizartinib is a novel oral Class III receptor tyrosine kinase (RTK) inhibitor exhibiting highly potent and selective but reversible inhibition of FMS-like tyrosine kinase FLT3. The dose will be adjusted for the patient's body weight (BW) as measured at the start of each course. Quizartinib will be administered orally once daily and is taken for 14 consecutive days during induction and consolidation courses. Induction course 1: Start on day 13; Induction course 2: Start on day 9; Consolidation course 1: Start on day 6; Consolidation courses 2 and 3 (only if no allo-SCT is done): Start on day 6. Continuation courses 1-6: patients will receive quizartinib for six 28-day courses. For the first 15 days of course 1 a starting dose will be applicable. On course 1 Day 16, the dose will be increased if the average QTc of the triplicate Electrocardiograms is ≤450 msec on course 1 Day 15. Once the dose is increased, the patient may continue on this dose as long as dose reduction is not needed.
DRUG	Etoposide	Induction course 1: 150 mg/m2 once daily by Intravenous (IV) infusion over 2 hours (+/- 30 mins) on days 1-5 inclusive (total 5 doses). Induction course 2: 150 mg/m2 once daily by IV infusion over 2 hours (+/- 30 mins) on days 6-8 inclusive (total 3 doses). Consolidation course 2 (only if no allo-SCT is done): 100 mg/m2 once daily by IV infusion over 1 hour (+/- 15 mins) on days 1-5 inclusive (total 5 doses).
DRUG	Dexrazoxane	Induction course 1: 250 mg/m2 once daily by 15 mins IV infusion shortly before Mitoxantrone on day 6-10 inclusive (total 5 days), per investigator discretion and per institutional guidelines and availability. Induction course 2: 600 mg/m2 once daily by 15 mins IV infusion shortly before daunorubicin on day 2,4,6 inclusive (total 3 does), per investigator discretion and per institutional guidelines and availability. Consolidation course 1: 500 mg/m2 once daily by 15 mins IV infusion shortly before Mitoxantrone on 3-5 inclusive (total 3 does), per investigator discretion and per institutional guidelines and availability.
DRUG	Mitoxantrone	Induction course 1: 5 mg/m2 once daily by IV infusion over 1 hour (+/- 15 mins) on days 6-10 inclusive (total 5 doses). Please note that mitoxantrone and cytarabine should not be given concomitantly. Mitoxantrone should be completed before cytarabine is given. Consolidation course 1: 10 mg/m2 once daily by IV infusion over 1 hour (+/- 15 mins) on days 3-5 inclusive (total 3 doses).
DRUG	Cytarabine	Induction course 1: 200 mg/m2 once daily by IV infusion over 12 hours (+/- 1 hour) on days 6-12 inclusive (total 7 doses), following mitoxantrone. Induction course 2: 100 mg/m2 once daily by continuous IV infusion on days 1-2 inclusive. And 100 mg/m2 twice daily as a 30min (+/- 10 mins) IV infusion every 12 hours on days 3-8 inclusive (total 12 doses). Consolidation course 1: 1000 mg/m2 twice daily by IV infusion over 2 hours (+/- 30 min) every 12 hours on days 1-3 inclusive (total 6 doses). Consolidation course 2 (only if no allo-SCT is done): 3000 mg/m2 twice daily by IV infusion over 2 hours (+/- 30 mins) every 12 hours on days 1-3 inclusive (total 6 doses). Consolidation course 3 (only if no allo-SCT is done): 2000 mg/m2 once daily by IV infusion over 3 hours (+/- 1 hour) starting 4 hours after fludarabine on days 1-5 inclusive (total 5 doses), following fludarabine.
DRUG	Methotrexate	Induction course 1: Methotrexate (MTX) Intrathecal therapy (IT) prophylaxis is age-adjusted. If MTX is given at diagnosis omit IT therapy on day 6 unless in case of CNS involvement (CNS3). For children with initial CNS involvement (CNS3) MTX IT is replaced with triple IT and given more frequently. For children with CNS2, CSF must be investigated on day 22; if leukemic cells persist, treat as CNS3. Induction course 2, Day 1: MTX (IT) prophylaxis is age-adjusted. For children with initial CNS involvement (CNS3) MTX IT is replaced with triple IT and given more frequently. Consolidation course 1, Day 1: MTX (IT) prophylaxis is age-adjusted. For children with initial CNS involvement (CNS3) MTX IT is replaced with triple IT and given more frequently. Consolidation course 2 and 3, Day 1 (only if no allo-SCT is done): MTX (IT) prophylaxis is age-adjusted. For children with initial CNS involvement (CNS3) MTX IT is replaced with triple IT and given more frequently.
DRUG	Daunorubicin	Induction course 2: 60 mg/m2 once daily by IV infusion over 1 hour (+/- 15 mins) on days 2,4,6 inclusive (total 3 doses).
DRUG	Fludarabine	Consolidation course 3 (only if no allo-SCT is done): 30 mg/m2 once daily by IV infusion over 30 mins (+/- 10 mins) on days 1-5 inclusive (total 5 doses).
OTHER	allo-SCT	The SCT procedure is left to the discretion of the investigator and not part of this protocol.

Timeline

• Start date: 2024-02-06
• Primary completion: 2028-06-01
• Completion: 2032-06-01
• First posted: 2024-02-16
• Last updated: 2025-08-05

Locations

1 site across 1 country: Netherlands

Regulatory

• FDA-regulated drug study