Flotetuzumab for the Treatment of Pediatric Recurrent or Refractory Acute Myeloid Leukemia
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|ClinicalTrials.gov Identifier: NCT04158739|
Recruitment Status : Active, not recruiting
First Posted : November 12, 2019
Last Update Posted : October 12, 2022
|Condition or disease||Intervention/treatment||Phase|
|Recurrent Acute Myeloid Leukemia Refractory Acute Myeloid Leukemia||Drug: Cytarabine Biological: Flotetuzumab||Phase 1|
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.
I. To characterize the pharmacokinetics of flotetuzumab in pediatric patients with relapsed or refractory AML.
II. To define preliminarily 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.
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 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.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||47 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||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|
|Actual Study Start Date :||January 6, 2020|
|Actual Primary Completion Date :||September 30, 2022|
|Estimated Study Completion Date :||October 3, 2023|
Experimental: Treatment (cytarabine, flotetuzumab)
Patients receive cytarabine 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.
- Dose limiting toxicities due to flotetuzumab [ Time Frame: Up to 29 days ]Frequency and proportion of patients experiencing dose limiting toxicities during cycle 1 that are possibly, probably, or definitely due to flotetuzumab by dose level and study part.
- Maximum tolerated dose and/or recommended phase 2 dose [ Time Frame: Up to 29 days ]Estimated maximum tolerated dose and/or recommended phase 2 dose.
- Area under the plasma concentration curve versus time of flotetuzumab [ Time Frame: Up to 29 days ]A descriptive analysis of the area under the plasma concentration curve versus time at steady state of flotetuzumab including median, minimum and maximum by dose level.
- Anti-drug antibody (ADA) production of flotetuzumab [ Time Frame: Up to 2 years ]ADA production will be summarized by medians with minimum and maximum values stratified by patient response (responder vs. non-responder).
- Change in T-lymphocyte population numbers [ Time Frame: Up to 180 days ]Changes in T cell number will be described and exploratory analysis will be conducted to assess their correlation with clinical features including occurrence of infections and response. Disease response will be assessed according to the revised acute myeloid leukemia (AML) International Working Group (IWG) criteria and will be reported descriptively. Analyses will be descriptive and exploratory and hypothesis-generating in nature.
- CD123 surface expression [ Time Frame: Baseline ]CD123 expression will be analyzed in an exploratory fashion, both using a binary scale and using a continuous scale to evaluate whether there are correlations between CD123 expression and anti-leukemia effects. Analyses will be descriptive and exploratory and hypothesis-generating in nature.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04158739
|Principal Investigator:||Adam J Lamble||Pediatric Early Phase Clinical Trial Network|