NCT04158739

Flotetuzumab for the Treatment of Pediatric Recurrent or Refractory Acute Myeloid Leukemia

A Phase 1 Trial of the CD123 X CD3 DART Molecule Flotetuzumab (NSC#808294) in Children, Adolescents, and Young Adults With Relapsed or Refractory Acute Myeloid Leukemia

• Status: Active Not Recruiting
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 16 (actual)
• Sponsor: Children's Oncology Group · Network
• Sex: All
• Age: 20 Years
• Healthy volunteers: Not accepted

Summary

This phase I trial studies the side effects, best dose of flotetuzumab and how well it works in treating patients with acute myeloid leukemia (AML) that has come back (recurrent) or has not responded to treatment (refractory). This study also determines the safest dose of flotetuzumab to use in children with AML. As an immunotherapy, flotetuzumab may also cause changes in the body's normal immune system, which are also under study in this trial.

Detailed description

PRIMARY OBJECTIVES: I. To assess the safety and tolerability of flotetuzumab administered by continuous intravenous (IV) infusion to pediatric patients \< 21 years of age with relapsed or refractory acute myeloid leukemia (AML). II. To estimate the maximum tolerated dose (MTD) and/or recommended phase 2 dose (RP2D) of flotetuzumab administered by continuous IV infusion to pediatric patients \< 21 years of age with relapsed or refractory AML. SECONDARY OBJECTIVES: I. To characterize the pharmacokinetics of flotetuzumab in pediatric patients with relapsed or refractory AML. II. To preliminarily define the anti-tumor activity of flotetuzumab within the confines of a phase 1 study and correlate potential activity with baseline disease burden at study entry. III. To monitor anti-drug antibody (ADA) production and characterize the immunogenicity of flotetuzumab. EXPLORATORY OBJECTIVES: I. To evaluate changes in T-lymphocyte population numbers before and after flotetuzumab treatment. II. To evaluate the tumor microenvironment and cytokine production by immune effector cells before and after flotetuzumab treatment. III. To quantify CD123 surface expression on AML cells at baseline and evaluate expression as a potential biomarker of flotetuzumab response. OUTLINE: This is a dose-escalation/dose de-escalation study of flotetuzumab. Patients receive cytarabine intrathecally (IT) on days -6 to 0 prior to cycle 1. Patients may receive additional doses of cytarabine on day 1 of subsequent cycles per physician discretion. Patients also receive flotetuzumab IV continuously for 28 days. Treatment repeats every 29 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed for 30 days.

Conditions

• Recurrent Acute Myeloid Leukemia
• Refractory Acute Myeloid Leukemia

Interventions

Type	Name	Description
DRUG	Cytarabine	Given IT
BIOLOGICAL	Flotetuzumab	Given IV

Timeline

• Start date: 2020-01-22
• Primary completion: 2022-09-30
• Completion: 2026-03-31
• First posted: 2019-11-12
• Last updated: 2026-01-23
• Results posted: 2023-12-11

Locations

19 sites across 1 country: United States

Regulatory

• FDA-regulated drug study