Effects of Anticoagulant Preventive Injection in Patients With Blood Cancer (METRO B)

Effects of Injection Tinzaparin Prophylactic Dose (4,500 IU Anti-Xa) on Thrombin Generation in Patients With Multiple Myeloma, Lymphoma Patients and Patients Hospitalized for an Acute Medical Condition.

In cancer, the incidence of venous thromboembolism (VTE) is particularly high in patients with myeloma, especially when it is de novo and treated with thalidomide, lenalidomide or erythropoietin. Curiously, the prevention of VTE with LMWH (low-molecular-weight heparin) in myeloma seems no more effective than that achieved with aspirin, while the effectiveness of the latter in the primary prevention of VTE has never been demonstrated regardless of the type of population considered. Meanwhile, a biological study showed that prophylactic doses of LMWH in patients with different types of cancer did not always optimal reduction of thrombin peak during the 24 hours following the injection of LMWH. These clinical and biological studies lead to the conclusion that patients with myeloma may be resistant to the usual doses of preventive LMWH, which may explain the failure of prevention.

Initially we intend to investigate whether this resistance to prophylactic doses of LMWH is present in patient's biology and if this resistance is specific to myeloma in hematological cancers. For this, we propose to study the evolution of thrombin generation by Thrombinography during 24 hours after subcutaneous injection of 4500 anti-Xa IU Tinzaparin in 6 patients with de novo myeloma whit high thrombo embolic risk ie treated with thalidomide, lenalidomide or erythropoietin. LMWH is Tinzaparin chosen because it does not accumulate in patients with impaired renal function, and has a greater anti-biological activity thrombotic than other LMWH.

To assess whether the observed pattern of thrombin generation is particularly multiple myeloma, we will take the same study in 6 patients with aggressive lymphoma and 6 medical patients hospitalized for acute heart and respiratory failure.

Study Overview

• Status: Completed
• Conditions: Lymphoma; Multiple Myeloma
• Intervention / Treatment: Drug: Tinzaparin; Other: Blood sample

• Study Type: Interventional
• Enrollment (Actual): 19
• Phase: Phase 2

Contacts and Locations

Study Locations

• France
  • Saint-Etienne, France, 42055
    • CHU de Saint-Etienne

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Body weight between 40 and 100 kg
2. Patient:

2a- With multiple myeloma indication with de novo standard treatment thalidomide or lenalidomide or erythropoietin (group 1) 2b- Or hospitalized for aggressive lymphoma treated with chemotherapy (group 2) 2c- Or older than 40 years and hospitalized at least three days for an acute medical pathology type of acute respiratory or cardiac (group 3) decompensation

Exclusion Criteria:

• Patient requiring anticoagulant therapy at curative doses
• Patients with a lower platelet count 80 G / L
• Subject with a history of heparin-induced thrombocytopenia
• Subject with a history of hemorrhagic disease
• History of severe trauma within 6 weeks prior to enrollment
• Organic lesion at risk of bleeding
• Poor renal with creatinine clearance <30 ml / min
• Hypersensitivity to Tinzaparin
• Events or bleeding tendencies associated with coagulation disorders
• Subject on oral anticoagulant
• For group 3: Presence of hematological malignancy or active cancer

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Patients with multiple myeloma; Patient with multiple myeloma indication with de novo standard treatment thalidomide or lenalidomide or erythropoietin treated with one injection of 4500 IU tinzaparin and blood samples taken at hours : 0, 3, 8, 18 and 24 after subcutaneous injection of tinzaparin	Drug: Tinzaparin; single subcutaneous injection of 4500 IU tinzaparin; Other: Blood sample; blood sample taken at hours 0, 3, 8, 18 and 24 after subcutaneous injection of 4500 IU tinzaparin
Active Comparator: Patients with agressive lymphoma; Patient hospitalized for aggressive lymphoma treated with chemotherapy treated with one injection of 4500 IU tinzaparin and blood samples taken at hours : 0, 3, 8, 18 and 24 after subcutaneous injection of tinzaparin	Drug: Tinzaparin; single subcutaneous injection of 4500 IU tinzaparin; Other: Blood sample; blood sample taken at hours 0, 3, 8, 18 and 24 after subcutaneous injection of 4500 IU tinzaparin
Active Comparator: Patients with acute medical condition; Patient older than 40 years and hospitalized at least three days for an acute medical pathology type of acute respiratory or cardiac treated with one injection of 4500 IU tinzaparin and blood samples taken at hours : 0, 3, 8, 18 and 24 after subcutaneous injection of tinzaparin	Drug: Tinzaparin; single subcutaneous injection of 4500 IU tinzaparin; Other: Blood sample; blood sample taken at hours 0, 3, 8, 18 and 24 after subcutaneous injection of 4500 IU tinzaparin

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Endogenous Thrombin Potential (ETP, nM.min) for all patients with de novo myeloma with high thrombotic risk	Endogenous Thrombin Potential (i.e. the aera under the thrombin generation curve, nM.min) is measured by Thromboplastin Generation Tests (TGTs) following a single injection of 4500 IU tinzaparin	hours : 0, 3, 8, 18, 24

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Endogenous Thrombin Potential (ETP, nM.min) for all patients with aggressive lymphoma treated with chemotherapy	Endogenous Thrombin Potential (i.e. the aera under the thrombin generation curve, nM.min) is measured by Thromboplastin Generation Tests (TGTs) following a single injection of 4500 IU tinzaparin	hours : 0, 3, 8, 18, 24
Endogenous Thrombin Potential (ETP, nM.min) for all patients with over 40 years hospitalized for heart or respiratory failure	Endogenous Thrombin Potential (i.e. the aera under the thrombin generation curve, nM.min) is measured by Thromboplastin Generation Tests (TGTs) following a single injection of 4500 IU tinzaparin	hours : 0, 3, 8, 18, 24
Differences of Endogenous Thrombin Potential (ETP, nM.min) between group 1 and group 2 et 3	Endogenous Thrombin Potential (i.e. the aera under the thrombin generation curve, nM.min) is measured by Thromboplastin Generation Tests (TGTs) following a single injection of 4500 IU tinzaparin	hours : 0, 3, 8, 18, 24

Collaborators and Investigators

• Sponsor: Centre Hospitalier Universitaire de Saint Etienne
• Collaborators: LEO Pharma
• Investigators: Principal Investigator: Bernard TARDY, PhD, CHU Saint-Etienne

Study record dates

Study Major Dates

• Study Start (Actual): April 14, 2015
• Primary Completion (Actual): May 9, 2017
• Study Completion (Actual): May 9, 2017

Study Registration Dates

• First Submitted: October 2, 2014
• First Submitted That Met QC Criteria: October 6, 2014
• First Posted (Estimate): October 9, 2014

Study Record Updates

• Last Update Posted (Actual): May 11, 2017
• Last Update Submitted That Met QC Criteria: May 10, 2017
• Last Verified: May 1, 2017

More Information

Terms related to this study

• Keywords: Multiple Myeloma; Lymphoma; thrombin generation; tinzaparin; Endogenous Thrombin Potential; Thromboplastin generation tests
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Hematologic Diseases; Hemorrhagic Disorders; Hemostatic Disorders; Paraproteinemias; Blood Protein Disorders; Lymphoma; Multiple Myeloma; Neoplasms, Plasma Cell; Molecular Mechanisms of Pharmacological Action; Fibrinolytic Agents; Fibrin Modulating Agents; Anticoagulants; Heparin, Low-Molecular-Weight; Tinzaparin; Dalteparin
• Other Study ID Numbers: 1408049; 2014-000946-31 (EudraCT Number)