Endothelial Activation Hemostasis Disturbances and Severe Bleeding Events in Hyperleukocytic Acute Myeloid Leukemia (HEAL)

Characterization of Endothelial Activation Hemostasis Disturbances and Severe Bleeding Events in Hyperleukocytic Acute Myeloid Leukemia

Hyper-leukocytosis > 50.109/L is observed in 15% of acute myeloid leukemia (AML).

Level of hyper-leukocytosis is linearly associated with the incidence of life threatening complications that lead to the early death in 25% of these patients.

The HEAL project is a prospective, uni-centric, observational study that plans to include a cohort of 50 patients presenting de novo AML with hyper-leukocytosis (HL) (> 50.109/L) and 10 controls. The aim of the study is to describe the relative proportion of various hemostasis components disturbances, endothelium alterations, platelet dysfunction and to calculate cumulative incidence of hemorrhagic and thrombotic complications as well as overall survival of patients presenting with HL AML.

Study Overview

• Status: Unknown
• Conditions: Leukemia, Myeloid, Acute

• Study Type: Observational
• Enrollment (Anticipated): 60

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Patients with acute myleoid leukemia associated to hyper-leukocytosis

Description

Inclusion Criteria:

• De novo AML
• GB counts > 50 G/L
• Eligible for intensive chemotherapy
• no previous AML treatment

Exclusion Criteria:

• secondary AML
• relapse of AML
• Acute promyelocytic leukemia
• Previous antiplatelet or anticoagulant treatment

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort
Cases; Patients with acute myeloid leukemia, associated to hyper leukocytosis
Control; Patients with acute myeloid leukemia, without hyper leukocytosis

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Hemostasis / platelet and endothelial dysfunction assessed by plasma concentration of ICAM-	plasma concentration of ICAM-	12hours after chemotherapy initiation
Hemostasis / platelet and endothelial dysfunction parameter assessed by plasma concentration of Syndecan-1	plasma concentration of Syndecan-1	12hours after chemotherapy initiation
Hemostasis / platelet and endothelial dysfunction parameter assessed by plasma concentration of vWF Ag	plasma concentration of vWF Ag	12hours after chemotherapy initiation
Hemostasis / platelet and endothelial dysfunction assessed by vWF activity	vWF activity	12hours after chemotherapy initiation
Hemostasis / platelet and endothelial dysfunction assessed by plasma concentration of Fg	plasma concentration of Fg	12hours after chemotherapy initiation
Hemostasis / platelet and endothelial dysfunction assessed by plasma concentration of t-PA	plasma concentration of t-PA	12hours after chemotherapy initiation
Hemostasis / platelet and endothelial dysfunction assessed by plasma concentration of u-PA	plasma concentration of u-PA	12hours after chemotherapy initiation
Hemostasis / platelet and endothelial dysfunction assessed by plasma concentration of e-Selectin	plasma concentration of e-Selectin	12hours after chemotherapy initiation
Hemostasis / platelet and endothelial dysfunction assessed by plasma concentration of sCD40L	plasma concentration of sCD40L	12hours after chemotherapy initiation
Hemostasis / platelet and endothelial dysfunction parameter assessed by plasma concentration of IL6	plasma concentration of IL6	12hours after chemotherapy initiation
Hemostasis / platelet and endothelial dysfunction assessed by plasma concentration of AT	plasma concentration of AT	12hours after chemotherapy initiation
Hemostasis / platelet and endothelial dysfunction assessed by plasma concentration of Fragments thrombin 1+2	plasma concentration of Fragments thrombin 1+2	12hours after chemotherapy initiation
Hemostasis / platelet and endothelial dysfunction assessed by plasma concentration of TAT complex	plasma concentration of TAT complex	12hours after chemotherapy initiation
Hemostasis / platelet and endothelial dysfunction assessed by plasma concentration of plasmin-antiplasmin complex	plasma concentration of plasmin-antiplasmin complex	12hours after chemotherapy initiation
Hemostasis / platelet and endothelial dysfunction assessed by plasma concentration of PAI-1 Ag	plasma concentration of PAI-1 Ag	12hours after chemotherapy initiation
Hemostasis / platelet and endothelial dysfunction assessed by plasma concentration of PAI-1 activity	plasma concentration of PAI-1 activity	12hours after chemotherapy initiation
Hemostasis / platelet and endothelial dysfunction assessed by plasma concentration of t-PA-PAI-1 complex	plasma concentration of t-PA-PAI-1 complex	12hours after chemotherapy initiation
Hemostasis / platelet and endothelial dysfunction assessed by plasma concentration of ADAMTS13 Ag	plasma concentration of ADAMTS13 Ag	12hours after chemotherapy initiation
Hemostasis / platelet and endothelial dysfunction assessed by ADAMTS13 activity	ADAMTS13 activity	12hours after chemotherapy initiation
Hemostasis / platelet and endothelial dysfunction assessed by plasma concentration of vWF:CB	plasma concentration of vWF:CB	12hours after chemotherapy initiation
Hemostasis / platelet and endothelial dysfunction assessed by plasma concentration of Fibrin monomers	plasma concentration of Fibrin monomers	12hours after chemotherapy initiation
Hemostasis / platelet and endothelial dysfunction assessed by Prothrombine Time	Prothrombine Time	12hours after chemotherapy initiation
Hemostasis / platelet and endothelial dysfunction assessed by Activated Partial Thromboplastin Time [APTT]	Activated Partial Thromboplastin Time [APTT]	12hours after chemotherapy initiation
Hemostasis / platelet and endothelial dysfunction assessed by plasma concentration of Factor IX	plasma concentration of Factor IX	12hours after chemotherapy initiation
Hemostasis / platelet and endothelial dysfunction assessed by plasma concentration of Factor II	plasma concentration of Factor II	12hours after chemotherapy initiation
Hemostasis / platelet and endothelial dysfunction assessed by plasma concentration of Factor VIII	plasma concentration of Factor VIII	12hours after chemotherapy initiation
Hemostasis / platelet and endothelial dysfunction assessed by plasma concentration of Factor XII	plasma concentration of Factor XII	12hours after chemotherapy initiation
Hemostasis / platelet and endothelial dysfunction assessed by plasma concentration of Factor X	plasma concentration of Factor X	12hours after chemotherapy initiation

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cumulative incidence of serious bleeding events	Time from inclusion to first serious bleeding event	1 month
Cumulative incidence of thrombotic events	Time from inclusion to first thrombotic event	1 month
Overall survival	Time from inclusion to death of any cause	1 month
ICU length of stay	duration of stay in ICU within the first month	1 month

Collaborators and Investigators

• Sponsor: Assistance Publique - Hôpitaux de Paris

Study record dates

Study Major Dates

• Study Start (Anticipated): October 1, 2019
• Primary Completion (Anticipated): February 1, 2022
• Study Completion (Anticipated): July 1, 2022

Study Registration Dates

• First Submitted: July 1, 2019
• First Submitted That Met QC Criteria: October 18, 2019
• First Posted (Actual): October 21, 2019

Study Record Updates

• Last Update Posted (Actual): October 21, 2019
• Last Update Submitted That Met QC Criteria: October 18, 2019
• Last Verified: June 1, 2019

More Information

Terms related to this study

• Keywords: hemostasis
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute
• Other Study ID Numbers: 190002

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No