Outcome of Acquired Haemophilia With Steroid Combined With Cyclophosphamide Versus Steroid Combined With Rituximab (CREHA Study)

This study is currently recruiting participants. (see Contacts and Locations)
Verified June 2014 by University Hospital, Rouen
Sponsor:
Information provided by (Responsible Party):
University Hospital, Rouen
ClinicalTrials.gov Identifier:
NCT01808911
First received: October 16, 2012
Last updated: June 18, 2014
Last verified: June 2014
  Purpose

CREHA project is a study comparing steroid combined with cyclophosphamide versus steroid combined with rituximab in patients with acquired haemophilia. The study will test the hypothesis that steroid combined with cyclophosphamide is more effective than steroid plus rituximab for FVIII inhibitor eradication in acquired haemophilia.


Condition Intervention Phase
Acquired Haemophilia
Drug: Steroid + cyclophosphamide
Drug: Steroid + rituximab
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Bio-equivalence Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Outcome of Acquired Haemophilia With Steroid Combined With Cyclophosphamide Versus Steroid Combined With Rituximab (CREHA Study)

Resource links provided by NLM:


Further study details as provided by University Hospital, Rouen:

Primary Outcome Measures:
  • Primary objective [ Time Frame: During 18 months ] [ Designated as safety issue: No ]
    Demonstrate the inferiority of steroid combined with rituximab as compared to the recommended immunosuppressive approach (steroid combined with cysclophosphamide for 21 to 42 days) as the first-line immunosuppressive therapy for FVIII inhibitor eradication in acquired haemophilia

  • Primary efficacy outcome [ Time Frame: During 18 months ] [ Designated as safety issue: No ]
    The primary efficacy outcome is the proportion of patients achieving complete remission defined as titer FVII inhibitor lower than 0.4 Bethesda unit and factor VIII level > 50%

  • Primary safety outcomes [ Time Frame: During 18 months ] [ Designated as safety issue: Yes ]
    The primary safety outcomes will be the occurrence of major bleeding and infection related immunosuppressive treatment adverse events.


Secondary Outcome Measures:
  • Secondary objective [ Time Frame: 6 months, 12 months and 18 months ] [ Designated as safety issue: No ]
    Secondary objective are time to complete remission, number of relapse at M6, M12, M18, adverse events (especially related to bleeding or to immunosuppressive treatment) and mortality

  • Other key safety outcome [ Time Frame: During 18 months ] [ Designated as safety issue: Yes ]
    The other key safety outcome are clinically relevant non major bleeding, diabetes and mortality non-related with acquired haemophilia or immunosuppressive therapy


Estimated Enrollment: 164
Study Start Date: May 2012
Estimated Study Completion Date: November 2018
Estimated Primary Completion Date: November 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Bras A
Steroid 1mg/kg/d and Cyclophosphamide 2mg/kg/d
Drug: Steroid + cyclophosphamide
Experimental: Bras B
Steroid 1mg/kg/d and Rituximab 375 mg/m2 every week during four weeks
Drug: Steroid + rituximab

Detailed Description:

CREHA project is a multicenter, randomized, controlled efficacity and safety study comparing steroid combined with cyclophosphamide versus steroid combined with rituximab in patients with acquired haemophilia. The study will test the hypothesis that steroid combined with cyclophosphamide is more effective than steroid plus rituximab for FVIII inhibitor eradication in acquired haemophilia

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • men or women
  • women post-menpausal or with ongoing contraception
  • 18 years old or more
  • diagnosis of acquired hemophilia
  • patient must be insured
  • patient has provided written informed consent prior to enrolment
  • patient compliant

Exclusion Criteria:

  • constitutional hemophilia
  • chemotherapy
  • ongoing treatment with prednisone > 20mg further more 1 month
  • ongoing treatment with prednisone >0.7 mg/d further more 10 days
  • thrombocytopenia
  • leukopenia
  • chronic disease
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01808911

Contacts
Contact: Hervé LEVESQUE, MD, PhD (0)2 32 88 90 01 ext +33 herve.levesque@chu-rouen.fr

Locations
France
University Hospital Amiens Recruiting
Amiens, France, 80054
Contact: Jean SCHMIDT, MD    (0)3 22 66 82 30 ext +33    schmidt.jean@chu-amiens.fr   
Principal Investigator: Jean SCHMIDT, MD         
Hospital Jean Verdier Recruiting
Bondy, France, 93140
Contact: Olivier FAIN, MD, PhD    (0)1 48 02 63 96 ext +33    olivier.fain@jvr.aphp.fr   
Principal Investigator: Olivier FAIN, MD, PhD         
Sub-Investigator: Yves LAURIAN, MD         
Hospital Ambroise Paré Recruiting
Boulogne-Billancourt, France, 92104
Contact: Thomas HANSLIK, MD, PhD    (0)1 49 09 56 38 ext +33    thomas.hanslik@apr.aphp.fr   
Principal Investigator: Thomas HANSLIK, MD, PhD         
University Hospital of Brest - Hospital La cavale Blanche Recruiting
Brest, France, 29609
Contact: Aurélien DELLUC, MD    (0)2 98 34 73 36 ext +33    aurelien.delluc@chu-brest.fr   
Principal Investigator: Aurélien DELLUC, MD         
Principal Investigator: Brigitte PAN-PETESCH, MD         
Hospital of Béziers Recruiting
Béziers, France, 34525
Contact: Eric OZIOL, MD    (0)4 67 35 70 56 ext +33    eric.oziol@ch-beziers.fr   
Principal Investigator: Eric OZIOL, MD         
University Hospital Côte de Nacre Recruiting
Caen, France, 14033
Contact: Boris BIENVENU, MD, PhD    (0)2 31 06 45 84 ext +33    bienvenu-b@chu-caen.fr   
Principal Investigator: Boris BIENVENU, MD, PhD         
University Hospital G. Montpied Recruiting
Clermont-Ferrand, France, 63003
Contact: Marc ANDRE, MD,PhD    (0)4 73 75 14 35 ext +33    mandre@chu-clermontferrand.fr   
Principal Investigator: Marc ANDRE, MD, PhD         
Hospital Henri Mondor Recruiting
Créteil, France, 94010
Contact: Marc MICHEL, MD, PhD    (0)1 49 81 20 76 ext +33    marc.michel@hmn.aphp.fr   
Principal Investigator: Marc MICHEL, MD, PhD         
University Hospital of Dijon - Hospital Général Recruiting
Dijon, France, 21033
Contact: Jean-François BESANCENOT, MD, PhD    (0)3 80 29 37 73 ext +33    jean-francois.besancenot@chu-dijon.fr   
Principal Investigator: Jean-François BESANCENOT, MD, PhD         
University Hospital Bocage Recruiting
Dijon, France, 21079
Contact: Bernard BONNOTTE, MD, PhD    (0)3 80 29 34 32 ext +33    bernard.bonnotte@chu-dijon.fr   
Principal Investigator: Bernard BONNOTTE, MD, PhD         
University Hospital Michallon Recruiting
Grenoble, France, 38043
Contact: Laurence BOUILLET, MD    (0)4 76 7655 20 ext +33    Lbouillet@chu-grenoble.fr   
Principal Investigator: Laurence BOUILLET, MD         
Hospital Kremlin-Bicêtre Recruiting
Le Kremlin-bicetre, France, 94270
Contact: Olivier LAMBOTTE, MD, PhD    (0)1 45 21 27 83 ext +33    olivier.lambotte@bct.aphp.fr   
Principal Investigator: Olivier LAMBOTTE, MD, PhD         
University Regional Hospital of Lille Recruiting
Lille, France, 59037
Contact: Marc LAMBERT, MD    (0)3 20 44 42 96 ext +33    marc.lambert@chru-lille.fr   
Principal Investigator: Marc LAMBERT, MD         
Sub-Investigator: Jenny GOUDEMAND, MD, PhD         
university Hospital of Limoges Recruiting
Limoges, France, 87042
Contact: Elizabeth VIDAL-CATHALA, MD,PhD    (0)5 55 05 66 41 ext +33    elisabeth.vidal@unilim.fr   
Principal Investigator: Elizabeth VIDAL-CATHALA, MD, PhD         
AP-HM, University Hospital La Conception Recruiting
Marseille, France, 13385
Contact: Nicolas SCHLEINITZ, MD, PhD    (0)4 91 38 35 01 ext +33    nicolas.schleinitz@ap-hm.fr   
Principal Investigator: Nicolas SCHLEINITZ, MD, PhD         
University Hospital Saint-Eloi Recruiting
Montpellier, France, 34295
Contact: Alain LE QUELLEC, MD, PhD    (0)4 67 33 70 17 ext +33    a-lequellec@chu-montpellier.fr   
Principal Investigator: Alain LE QUELLEC, MD, PhD         
Regional Center of Haemophilia Treatment (CRTH) de Lorraine Not yet recruiting
Nancy, France
Contact: Brigit FROTSCHER, MD    (0) 03 83 15 37 84 ext +33    b.frotscher@chu-nancy.fr   
Principal Investigator: Brigit FROTSCHER, MD         
University Hospital of Nantes, Hospital Hôtel-Dieu Recruiting
Nantes, France, 44093
Contact: Mohamed HAMIDOU, MD, PhD    (0)2 40 08 31 46 ext +33    mohamed.hamidou@chu-nantes.fr   
Principal Investigator: Mohamed HAMIDOU, MD, PhD         
Principal Investigator: Marc TROSSAËRT, MD         
Hospital Archet 1 Not yet recruiting
Nice, France, 06202
Contact: Pierre-Yves JEANDEL, MD    (0)4 92 03 58 23 ext +33    jeandel.p@chu-nice.fr   
Principal Investigator: Pierre-Yves JEANDEL, MD         
Europen Hospital of Georges Pompidou (HEGP) Recruiting
Paris, France, 75908
Contact: Jacques POUCHOT, MD, PhD    (0)1 56 09 33 32 ext +33    jacques.pouchot@egp.aphp.fr   
Principal Investigator: Jacques POUCHOT, MD, PhD         
Hospital Saint-Louis Not yet recruiting
Paris 10e, France, 75475
Contact: Dominique FARGE-BANCEL, MD, PhD    (0)1 42 49 97 67 ext +33    dominique.farge-bancel@sls.aphp.fr   
Principal Investigator: Dominique FARGE-BANCEL, MD, PhD         
Hospital Pitié-Salpêtrière Recruiting
Paris 13e, France, 75651
Contact: Zahir AMOURA, MD, PhD    (0)1 42 17 80 01 ext +33    zahir.amoura@psl.aphp.fr   
Principal Investigator: Zahir AMOURA, MD, PhD         
Hospital Cochin Not yet recruiting
Paris 14e, France, 75679
Contact: Philippe BLANCHE, MD    (0)1 58 41 21 26 ext +33    philippe.blanche@cch.aphp.fr   
Principal Investigator: Philippe BLANCHE, MD         
Hospital Bichat Recruiting
Paris 18e, France, 75018
Contact: Thomas PAPO, MD, PhD    (0)1 40 25 87 05 ext +33    thomas.papo@bch.aphp.fr   
Principal Investigator: Thomas PAPO, MD, PhD         
University Hospital of Bordeaux - Hospital Haut-Lévêque Recruiting
Pessac, France, 33604
Contact: Jean-François VIALLARD, MD, PhD    (0)5 57 65 64 83 ext +33    jean-francois.viallard@chu-bordeaux.fr   
Principal Investigator: Jean-François VIALLARD, MD, PhD         
Hospital Lyon Sud Recruiting
Pierre-Benite, France, 69495
Contact: Isabelle DURIEU, MD, PhD    (0)4 78 86 14 65 ext +33    Isabelle.durieu@chu-lyon.fr   
Principal Investigator: Isabelle DURIEU, MD, PhD         
University Hospital of Poitiers Recruiting
Poitiers, France, 86021
Contact: Pascal ROBLOT, MD, PhD    (0) 5 49 44 44 22 ext +33    p.roblot@chu-poitiers.fr   
Principal Investigator: Pascal ROBLOT, MD, PhD         
Hospital Sud / Hospital Pontchaillou Recruiting
Rennes, France, 35000
Contact: Patrick JEGO, MD, PhD    (0)2 99 26 71 28 ext +33    patrick.jego@chu-rennes.fr   
Principal Investigator: Patrick JEGO, MD, PhD         
Sub-Investigator: Benoît GUILLET, MD         
University Hospital of Rouen Recruiting
Rouen, France, 76031
Contact: Hervé LEVESQUE, MD, PhD    (0) 2 32 88 90 01 ext +33    herve.levesque@chu-rouen.fr   
Contact: Ygal BENHAMOU, MD    (0)2 32 88 90 14 ext +33    ygal.benhamou@chu-rouen.fr   
Principal Investigator: Hervé LEVESQUE, MD, PhD         
Sub-Investigator: Ygal BENHAMOU, MD         
Sub-Investigator: Loïc BEGARIN, MD         
Sub-Investigator: Cyrielle ASSIE-CHAUVIER, MD         
Sub-Investigator: Nicolas GIRSZYN, MD         
Sub-Investigator: Alice PROUX, MD         
Sub-Investigator: Severine JOSSE, MD         
Sub-Investigator: Isabelle MARIE, MD, PhD         
Sub-Investigator: Jeanne-Yvonne BORG, MD, PhD         
Sub-Investigator: Véronique LE CAM-DUCHEZ, Md         
Hospital Nord Recruiting
Saint-Etienne, France, 42055
Contact: Pascal CATHEBRAS, MD, PhD    (0)4 77 82 83 42 ext +33    pascal.cathebras@chu-st-etienne.fr   
Principal Investigator: Pascal CATHEBRAS, MD, PhD         
University Regional Hospital Hautepierre Recruiting
Strasbourg, France, 67098
Contact: Anne BOUGARIT, MD, PhD    (0)3 88 12 75 94 ext +33    anne.bourgarit-durand@chur-strasbourg.fr   
Principal Investigator: Anne BOURGARIT, MD, PhD         
Sub-Investigator: Bernard GOICHOT, MD, PhD         
Sub-Investigator: Lélia GRUNEBAUM-HIMY, MD         
Sub-Investigator: Dominique DESPREZ, MD         
Hospital Purpan Recruiting
Toulouse, France, 31059
Contact: Laurent SAILLER, MD, PhD    (0)5 61 77 96 78 ext +33    sailler.l@chu-toulouse.fr   
Principal Investigator: Laurent SAILLER, MD, PhD         
Sub-Investigator: Marie-France THIERCELIN-LEGRAND, MD         
Sub-Investigator: Daniel ADOUE, MD, PhD         
Hospital Rangueil Recruiting
Toulouse, France, 31059
Contact: Dominique CHAUVEAU, MD, PhD    (0)5 61 32 32 79 ext +33    chauveau.d@chu-toulouse.fr   
Principal Investigator: Dominique CHAUVEAU, MD, PhD         
Sub-Investigator: Pierre SIE, MD, PhD         
Sub-Investigator: Sophie VOISIN, MD         
Hopsital Bretonneau Recruiting
Tours, France, 37044
Contact: François MAILLOT, MD, PhD    (0)2 47 47 47 27 ext +33    maillot@med.univ-tours.fr   
Principal Investigator: Francois MAILLOT, MD, PhD         
Sub-Investigator: Yves GRUEL, MD         
Sponsors and Collaborators
University Hospital, Rouen
  More Information

No publications provided

Responsible Party: University Hospital, Rouen
ClinicalTrials.gov Identifier: NCT01808911     History of Changes
Other Study ID Numbers: 2011/090/HP
Study First Received: October 16, 2012
Last Updated: June 18, 2014
Health Authority: France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)

Keywords provided by University Hospital, Rouen:
Acquired haemophilia
Comparative and randomized study
Cyclophosphamide
Rituximab

Additional relevant MeSH terms:
Hemophilia A
Blood Coagulation Disorders, Inherited
Blood Coagulation Disorders
Hematologic Diseases
Coagulation Protein Disorders
Hemorrhagic Disorders
Genetic Diseases, Inborn
Cyclophosphamide
Rituximab
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antirheumatic Agents
Therapeutic Uses
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists

ClinicalTrials.gov processed this record on August 21, 2014