NCT02791919

Wee1 Kinase Inhibitor AZD1775 and Combination Chemotherapy in Treating Children, Adolescents and Young Adults With Relapsed or Refractory Acute Myeloid Leukemia

A Phase 1 Trial of the Wee1 Kinase Inhibitor AZD1775 in Combination With Flag Chemotherapy in Children, Adolescents, and Young Adults With Relapsed or Refractory Acute Myeloid Leukemia

• Status: Withdrawn
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 0 (actual)
• Sponsor: National Cancer Institute (NCI) · NIH
• Sex: All
• Age: 1 Year – 21 Years
• Healthy volunteers: Not accepted

Summary

This phase I trial studies the side effects and best dose of wee1 kinase inhibitor AZD1775 when given together with fludarabine, cytarabine, and filgrastim (FLAG) combination chemotherapy in treating children, adolescents and young adults with relapsed or refractory acute myeloid leukemia. Wee1 kinase inhibitor AZD1775 may help combination chemotherapy work better by making tumor cells more sensitive to the drugs. Drugs used in chemotherapy, such as fludarabine and cytarabine, may prevent tumor cells from multiplying by damaging their deoxyribonucleic acid (DNA), which in turn stops the tumor from growing. Giving wee1 kinase inhibitor AZD1775 and FLAG chemotherapy may work better in treating patients with acute myeloid leukemia.

Detailed description

PRIMARY OBJECTIVES: I. To estimate the maximum tolerated dose (MTD) and/or recommended phase 2 dose of wee1 kinase inhibitor AZD1775 (AZD1775) administered orally daily for 5 days in combination with FLAG (fludarabine, cytarabine, filgrastim) chemotherapy in children and adolescents with recurrent or refractory acute myeloid leukemia (AML). II. To define and describe the toxicities of AZD1775 in combination with FLAG chemotherapy administered on this schedule. III. To characterize the pharmacokinetics AZD1775 in combination with FLAG chemotherapy in pediatric patients with relapsed or refractory AML. SECONDARY OBJECTIVES: I. To preliminarily define the antitumor activity of AZD1775 plus FLAG within the confines of a phase 1 study. II. To evaluate pharmacodynamic biomarkers of wee1 inhibition with administration of AZD1775 including cyclin-dependent kinase 1 (CDC2) phosphorylation at tyrosine 15 (Tyr15) and induction of gamma H2AX in pre- and post-treatment leukemic blasts. III. To explore mechanisms of apoptosis induction and cell death in leukemic blasts treated with AZD1775 plus chemotherapy. IV. To identify genomic alterations in leukemic blasts that may correlate with response to therapy with AZD1775 plus FLAG chemotherapy. OULTINE: This is a phase I dose escalation study of wee1 kinase inhibitor AZD1775. Patients receive filgrastim intravenously (IV) or subcutaneously (SC) daily, fludarabine intravenously IV over 30 minutes, cytarabine IV over 1-3 hours and wee1 kinase inhibitor AZD1775 orally (PO) on days 1-5. Patients who meet criteria for complete remission (CR), complete remission with partial recovery of platelet count (CRp) or partial response (PR) may receive a second course of therapy. Courses repeat every 28 days for up to 2 courses in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up periodically.

Conditions

• CNS 2a
• CNS 2b
• CNS 2c
• CNS1
• Recurrent Adult Acute Myeloid Leukemia
• Recurrent Childhood Acute Myeloid Leukemia

Interventions

Type	Name	Description
DRUG	Cytarabine	Given IV or IT
BIOLOGICAL	Filgrastim	Given IV or SC
DRUG	Fludarabine Phosphate	Given IV
OTHER	Laboratory Biomarker Analysis	Correlative studies
OTHER	Pharmacological Study	Correlative studies
DRUG	WEE1 Inhibitor AZD1775	Given PO

Timeline

• Start date: 2017-05-25
• Primary completion: 2019-05-31
• Completion: 2019-05-31
• First posted: 2016-06-07
• Last updated: 2017-05-03

Regulatory

• FDA-regulated drug study