Hydroxyurea Versus Aspirin and Hydroxyurea in Essential Thrombocythemia

NCT02611973 | Unknown Phase 3 DMC

• 1 other identifier: P140933
• Study Type: interventional
• Target: 2,250
• Locations: 1 country
• Sites: 1

Brief Summary

The hypothesis is that efficient prevention of thrombosis with aspirin at diagnosis becomes less useful once patients have achieved a hematologic response (HR) (modified by amendment 1/03/2017) and/or that this benefit is hampered by an increased hemorrhagic risk especially in elderly patients. Hence, investigator propose a prospective randomized study to assess the benefit / risk ratio of aspirin maintenance in high risk Essential thrombocythemia (ET) patients, in hematological response (modified by amendment 1/03/2017) on Hydroxyurea.

Conditions

MPN; Essential Thrombocythemia

Keywords

Essential Thrombocythemia; Aspirin

Outcome Measures

Primary Outcomes (1)

• Cumulative incidence of death from vascular origin and other thrombotic and hemorrhagic events (combined endpoint)

  Definition of vascular events: Thrombotic events: Myocardial infarction, unstable angina, stroke, transient ischemic attack, peripheral arterial thrombosis, splanchnic or limb deep vein thrombosis, pulmonary embolism, and erythromelalgia Hemorrhagic events: Intracranial or retroperitoneal bleed, overt hemorrhage associated with a decrease in hemoglobin ≥20 g/l or overt hemorrhage requiring a blood transfusion of two red blood cell (RBC) units or more, and hemorrhage of grade \>=2 according to the NCI Common Toxicity criteria (CTC) V.4.0 scale. Deaths will be included as a death from thrombosis or hemorrhage if they satisfied criteria for one of the above diagnoses immediately ANTE-MORTEM or if they had a POST-MORTEM examination confirming the diagnosis. Sudden death of presumed vascular origin without a POST-MORTEM examination will be included as a thrombotic death.

  at 2-years follow-up

Secondary Outcomes (19)

• Cumulative incidence and characteristics of vascular complications: thrombosis and hemorrhage, (grade, site, recurrence), assessed yearly over a 5-year follow-up period.

  at 5 years

• Rate of hematological response every 6 months

  at 5 years

• Adverse event (AE) frequency and incidence, comparison in the two arms

  at 5 years

• Number of HU-related nonhematologic toxicities

  at 5 years

• Cumulative incidence of thrombosis

  at 5 years

Study Arms (3)

HU without aspirin

EXPERIMENTAL

Other: Aspirin therapy interruption; Drug: Hydroxyurea treatment (HU)

HU + aspirin maintenance

ACTIVE COMPARATOR

Other: Usual treatment by aspirin 100 mg/d in the active comparator arm; Drug: Hydroxyurea treatment (HU)

HU + AAG

OTHER

Observational arm

Other: No interruption of aspirin in the Observational arm; Drug: Hydroxyurea treatment (HU)

Interventions

Aspirin therapy interruption OTHER

Stop the treatment by aspirin 100mg/d in the experimental arm.

HU without aspirin

Usual treatment by aspirin 100 mg/d in the active comparator arm OTHER

HU+ aspirin maintenance

HU + aspirin maintenance

No interruption of aspirin in the Observational arm OTHER

patient with Contre indication to aspirin or required antithrombotic therapy

HU + AAG

Hydroxyurea treatment (HU) DRUG

HU maintenance

HU + AAG; HU + aspirin maintenance; HU without aspirin

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• \> 18 years and older (modified by amendment 01/03/2017)
• Contraception considered effective by the investigator: for women of childbearing and for men whose partner is likely to procreate (added by amendment 01/03/2017)
• Diagnosis of ET performed within the last 10 years (modified by amendment 01/03/2017) : with or without Janus kinase 2V617F (JAK2V617F) mutation according to the WHO 2008 criteria (TEFFERI,2007)
• Signed Written Informed Consent
• Health insurance coverage.

You may not qualify if:

• Other myeloproliferative disorder than ET.
• Contra-indication to hydroxyurea.
• History of haemostasis perturbation not related to ET, associated with a significant risk of hemorrhage or thrombosis (modified by amendment 01/03/2017)
• Pregnancy or breastfeeding (added by amendment 01/03/2017)
• Inability to freely provide consent through judiciary or administrative condition.

Sponsors & Collaborators

• Assistance Publique - Hôpitaux de Paris: lead

Study Sites (1)

Henri Mondor Hospital

Créteil, 94010, France

RECRUITING

Related Publications (5)

• Alvarez-Larran A, Pereira A, Arellano-Rodrigo E, Hernandez-Boluda JC, Cervantes F, Besses C. Cytoreduction plus low-dose aspirin versus cytoreduction alone as primary prophylaxis of thrombosis in patients with high-risk essential thrombocythaemia: an observational study. Br J Haematol. 2013 Jun;161(6):865-71. doi: 10.1111/bjh.12321. Epub 2013 Apr 12.

  PMID: 23577924 BACKGROUND

• Barbui T, Barosi G, Birgegard G, Cervantes F, Finazzi G, Griesshammer M, Harrison C, Hasselbalch HC, Hehlmann R, Hoffman R, Kiladjian JJ, Kroger N, Mesa R, McMullin MF, Pardanani A, Passamonti F, Vannucchi AM, Reiter A, Silver RT, Verstovsek S, Tefferi A; European LeukemiaNet. Philadelphia-negative classical myeloproliferative neoplasms: critical concepts and management recommendations from European LeukemiaNet. J Clin Oncol. 2011 Feb 20;29(6):761-70. doi: 10.1200/JCO.2010.31.8436. Epub 2011 Jan 4.

  PMID: 21205761 BACKGROUND

• Barosi G, Birgegard G, Finazzi G, Griesshammer M, Harrison C, Hasselbalch HC, Kiladjian JJ, Lengfelder E, McMullin MF, Passamonti F, Reilly JT, Vannucchi AM, Barbui T. Response criteria for essential thrombocythemia and polycythemia vera: result of a European LeukemiaNet consensus conference. Blood. 2009 May 14;113(20):4829-33. doi: 10.1182/blood-2008-09-176818. Epub 2009 Mar 10.

  PMID: 19278953 BACKGROUND

• Barosi G, Mesa R, Finazzi G, Harrison C, Kiladjian JJ, Lengfelder E, McMullin MF, Passamonti F, Vannucchi AM, Besses C, Gisslinger H, Samuelsson J, Verstovsek S, Hoffman R, Pardanani A, Cervantes F, Tefferi A, Barbui T. Revised response criteria for polycythemia vera and essential thrombocythemia: an ELN and IWG-MRT consensus project. Blood. 2013 Jun 6;121(23):4778-81. doi: 10.1182/blood-2013-01-478891. Epub 2013 Apr 16.

  PMID: 23591792 BACKGROUND

• Barosi G, Birgegard G, Finazzi G, Griesshammer M, Harrison C, Hasselbalch H, Kiladijan JJ, Lengfelder E, Mesa R, Mc Mullin MF, Passamonti F, Reilly JT, Vannucchi AM, Barbui T. A unified definition of clinical resistance and intolerance to hydroxycarbamide in polycythaemia vera and primary myelofibrosis: results of a European LeukemiaNet (ELN) consensus process. Br J Haematol. 2010 Mar;148(6):961-3. doi: 10.1111/j.1365-2141.2009.08019.x. Epub 2009 Nov 23. No abstract available.

  PMID: 19930182 BACKGROUND

MeSH Terms

Conditions

Thrombocythemia, Essential

Condition Hierarchy (Ancestors)

Blood Coagulation Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Thrombocytosis; Blood Platelet Disorders; Myeloproliferative Disorders; Bone Marrow Diseases; Hemorrhagic Disorders

Study Officials

• Stéphane Giraudier, MD, PhD

  Assistance Publique - Hôpitaux de Paris

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Stéphane Giraudier, MD, PhD

CONTACT

(0)149812880; stephane.giraudier@aphp.fr

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 13, 2015
• First Posted: November 23, 2015
• Study Start: March 10, 2016
• Primary Completion: November 1, 2019
• Study Completion: November 1, 2022
• Last Updated: July 26, 2017

Record last verified: 2017-07

Locations

FR (1)