Allogeneic Hematopoietic Stem Cell Transplantation After Reduced-intensity Conditioning for Relapsed Follicular Lymphoma (RITALLO)

This study is currently recruiting participants. (see Contacts and Locations)
Verified August 2014 by University Hospital, Bordeaux
Sponsor:
Collaborator:
Roche Pharma AG
Information provided by (Responsible Party):
University Hospital, Bordeaux
ClinicalTrials.gov Identifier:
NCT01208896
First received: September 23, 2010
Last updated: August 19, 2014
Last verified: August 2014
  Purpose

This trial will evaluate the efficacy and the safety of a strategy of allogeneic stem cell transplantation including Rituximab in the conditioning regimen for the treatment of relapsed follicular lymphoma. The rationale for using Rituximab relies on a better control of the disease and a better prophylaxis of the graft versus host disease.


Condition Intervention Phase
Lymphoma, Follicular
Stem Cell Transplantation
Drug: Reduced_intensity conditioning
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Safety and Efficacy of a Strategy of Allogeneic Hematopoietic Stem Cell Transplantation After Reduced-intensity Conditioning for Chemosensitive Relapsed Follicular Lymphoma

Resource links provided by NLM:


Further study details as provided by University Hospital, Bordeaux:

Primary Outcome Measures:
  • Overall survival [ Time Frame: 2 year ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Toxic mortality [ Time Frame: 2 year ] [ Designated as safety issue: Yes ]
  • Progression free survival [ Time Frame: 2 year ] [ Designated as safety issue: No ]
  • Incidence of relapse [ Time Frame: 2 year ] [ Designated as safety issue: No ]
  • Grade II-IV acute GVHD incidence [ Time Frame: 2 year ] [ Designated as safety issue: No ]
  • Chronic GVHD incidence [ Time Frame: 2 year ] [ Designated as safety issue: No ]
  • Morbidity and adverse event [ Time Frame: 2 year ] [ Designated as safety issue: No ]
  • Hematologic reconstitution, Immunologic reconstitution, Chimerism [ Time Frame: 2 years ] [ Designated as safety issue: No ]

Estimated Enrollment: 33
Study Start Date: February 2011
Estimated Study Completion Date: February 2017
Estimated Primary Completion Date: February 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Rituximab Drug: Reduced_intensity conditioning
The conditioning regimen is composed of Fludarabine (30 mg/m2) and Cyclophosphamide (750 mg/m2), both administered intravenously at Days -5, -4, -3 with Day 0 being the day of transplantation. Rituximab will be administered intravenously at 375 mg/m2 at Day -13 and 1000 mg/m2 at Days -6, +1, +8. Tacrolimus and low-doses of methotrexate will be used for prophylaxis of GVHD.

Detailed Description:

Follicular lymphomas are chemosensitive neoplasms characterized by a relentless succession of remissions and relapses when treated with conventional chemotherapy. The successive periods of remission are of shorter duration and patients invariably die of their disease. At first line, patients are treated with conventional chemotherapy. At first relapse, intensive chemotherapy with autologous stem cell transplantation (SCT) is often proposed.

Allogeneic hematopoietic stem cell transplantation after reduced-intensity conditioning (RIC-allo) is an option for patients relapsing after autologous SCT, allowing long-term progression free survival of 50 to 60%. The toxic mortality related to severe acute graft versus host disease (GVHD) remains a critical issue. The goal of our study is to test in a multicentric approach a strategy of RIC-allo including rituximab in order to reduce the incidence of acute GVHD.

Around half of patients with relapsed or refractory follicular lymphomas treated with allogeneic SCT achieve long-term progression free survival whatever the conditioning regimen. Because the median age of patients with follicular lymphoma is 55 years, a reduced intensity conditioning is the most appropriate option in this setting. The outcome of patients with a chemoresistant disease is usually poor because of a high toxic mortality. As a consequence, only patients with a chemosensitive disease will be included in this study. To further reduce the toxic mortality, it is critical to reduce the incidence of severe acute GVHD. A low incidence of acute GVHD could be obtained by the use of Rituximab before and after the transplantation as reported by the MD Anderson's experience in several hematological malignancies including follicular lymphoma. Their results are impressive in patients with follicular lymphoma with long-term survival of 85%. The favored hypothesis is a depletion of patient and donor B cells reducing the presentation of minor histocompatibility alloantigens. The benefit of Rituximab could also be explained by its anti-lymphoma effects that could compensate the putative reduction of a graft versus lymphoma effect due to a better control of GVHD.

The primary objective is to estimate 2-year overall survival in this setting.

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Age ≥ 18 and ≤ 65 years
  • Follicular lymphoma confirmed by a biopsy at the last relapse.
  • 2nd, 3rd or 4th complete or partial response according to Cheson's criteria 1 (Annexe 1)
  • Relapse after autologous-SCT except if the absence of autologous SCT is due to a failure of collecting peripheral stem cells or investigator decision to not proceed to the autologous graft because of serious criteria
  • Relapse after at least one line of treatment with rituximab
  • Karnofsky index > 70%
  • HLA Matched related or unrelated donor (10/10 matching; HLA-A, HLA-B, HLA-C, HLA-DRB1, HLA-DQB1)
  • Signed informed consent

Exclusion Criteria:

  • Stable or progressive disease according to Cheson's criteria1 (Annexe 1)
  • Absence of treatment with rituximab before the last relapse
  • Cardiac insufficiency (ejection fraction < 50% by echocardiography)
  • Pulmonary disease characterized by DLCO < 60%
  • Renal insufficiency (clearance of creatinin < 60 ml/min)
  • Hepatic disease characterized by ASAT and/or ALAT and/or total bilirubin > 2 times the upper normal value except in case of Gilbert's disease or hepatic lymphoma
  • HIV positive test
  • Bacterial, Viral or Fungal uncontrolled infections
  • Pregnant or breast feeding woman
  • Cancer in the last 5 years except in case of cutaneous baso-cellular cancer or epithelioma "in situ" of the uterine cervix
  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: NCT01208896

Contacts
Contact: Stéphane VIGOUROUX, MD (33)5 57 65 65 11 stephane.vigouroux@chu-bordeaux.fr
Contact: Cyril MELOT, CRA (33)5 57 65 65 11 cyril.melot@chu-bordeaux.fr

Locations
France
University Hospital Angers Not yet recruiting
Angers Cedex 01, Angers, France, 49033
Contact: Martine GARDEMBAS-PAIN, Dr    02.41.35.47.05    MaGardembas@chu-angers.fr   
Sub-Investigator: GUARDIOLAT, MD         
Sub-Investigator: FRANCOIS, MD         
Service Hématologie, Hôpital Minjoz Not yet recruiting
Besançon, France, 25030
Principal Investigator: Eric DECONINCK         
Sub-Investigator: Fabrice LAROSA, MD         
Sub-Investigator: Katell LE DU, MD         
Sub-Investigator: Fatémeh LEGRAND-IZADIFAR, MD         
Service des maladies du sang - Hôpital Haut-Lévêque - avenue de magellan Not yet recruiting
Bordeaux - Pessac, France, 33600
Sub-Investigator: Krimo BOUABDALLAH, MD         
Sub-Investigator: Noel MILPIED         
Sub-Investigator: Reza TABRIZI         
Principal Investigator: Stephane VIGOUROUX         
Service Hématologie, Hôpital Augustin Morvan Recruiting
Brest, France, 29609
Principal Investigator: Christian BERTHOU         
Sub-Investigator: Gaëlle GUILLERM         
University Hospital, Caen Recruiting
Caen, France
Principal Investigator: Oumedaly REMAN, MD         
Sub-Investigator: Stephane CHEZE, MD         
Sub-Investigator: Margaret MACRO, MD         
Sub-Investigator: Hyacinthe JOHNSON-ANSAH, MD         
Sub-Investigator: Khaled BANABED, MD         
Sub-Investigator: Sylvain CHANTEPIE, MD         
Sub-Investigator: Michel LEPORRIER, MD         
Service Hématologie et Thérapie cellulaire, Pavillon Villemin Pasteur, CHU Clermont-Ferrand Recruiting
Clermont-Ferrand, France, 63000
Principal Investigator: Olivier TOURNILHAC         
Sub-Investigator: Carine CHALETEIX         
Sub-Investigator: Benoit de RENZIS         
Sub-Investigator: Eric HERMET         
Principal Investigator: Jacques-Olivier BAY, MD         
Sub-Investigator: Romain GUIEZE, MD         
Sub-Investigator: Victoria CACHEUX, MD         
CHU Grenoble Not yet recruiting
Grenoble, France, 38043
Contact: Claude-eric BULABOIS         
Principal Investigator: Claude-Eric BULABOIS         
CHRU Lille Recruiting
Lille, France, 59037
Contact: Ibrahim YAKOUB-AGHA         
Principal Investigator: Ibrahim YAKOUB-AGHA         
CHU Limoges Not yet recruiting
Limoges, France, 87042
Contact: Pascal TURLURE         
Principal Investigator: Pascal TURLURE         
Hôpital Edouard Herriot Not yet recruiting
Lyon, France, 69374
Contact: Mauricette MICHALLET, MD    04 72 11 74 01    mauricette.michallet@chu-lyon.fr   
Principal Investigator: Mauricette MICHALLET, MD         
Sub-Investigator: Franck NICOLINI, MD         
Sub-Investigator: Xavier-Georges THOMAS, MD         
Sub-Investigator: Sophie DUCASTELLE-LEPRETRE, MD         
Sub-Investigator: Giovanna CANNAS, MD         
Sub-Investigator: Fiorenza BARRACO, MD         
Sub-Investigator: Nicolae Claudiu PLESA, MD         
Sub-Investigator: Emmanuelle NICOLAS-VIRELIZIER, MD         
Service Hématologie Oncologie, Hôpital Lapeyronie, CHU de Montpellier Not yet recruiting
Montpellier, France, 34295
Sub-Investigator: Nathalie FEGUEUX         
Sub-Investigator: Patrice CEBALLOS         
Principal Investigator: Jean-François ROSSI         
Sub-Investigator: Jean Côme MENIANE         
CHU Nancy Not yet recruiting
Nancy, France, 54511
Contact: Pierre FEUGIER         
Principal Investigator: Pierre FEUGIER         
Service Hématologie Clinique, CHU -Hôtel Dieu Not yet recruiting
Nantes, France, 44093
Sub-Investigator: Patrice CHEVALLIER         
Sub-Investigator: Thierry GUILLAUME         
Principal Investigator: Mohamad MOHTY, MD         
Service Hématologie Clinique, Hôpital Archet 1 Not yet recruiting
Nice, France, 06202
Principal Investigator: Anne SIRVENT, MD         
Sub-Investigator: Nicole GRATECOS, MD         
Sub-Investigator: Nicolas MOUNIER, MD         
APHP Hôpital Saint Louis Recruiting
Paris, France, 75475
Contact: Gérard SOCIE         
Principal Investigator: Gérard SOCIE         
APHP Hôpital Henri-Mondor Recruiting
Paris, France, 94010
Contact: Corinne HAOUIN         
Principal Investigator: Corinne HAOUIN         
APHP Hôpital Necker-Enfants malades Not yet recruiting
Paris, France, 75015
Contact: Agnès BUZYN         
Principal Investigator: Agnès BUZYN         
APHP Hôpital Pitié-Salpêtrière Recruiting
Paris, France, 75651
Contact: Nathalie DHEDIN         
Principal Investigator: Nathalie DHEDIN         
CHU Poitiers - La Milétrie Not yet recruiting
Poitiers, France, 86000
Contact: Natacha MAILLARD         
Principal Investigator: Natacha MAILLARD         
Service Hématologie Clinique, Hôpital Pontchaillou Recruiting
Rennes, France, 35033
Sub-Investigator: Thierry LAMY DE LA CHAPELLE         
Sub-Investigator: Charles Dauriac         
Sub-Investigator: Martine Escoffre-Barbe         
Principal Investigator: Marc Bernard         
Sub-Investigator: Sophie De Guibert         
Sub-Investigator: Stanislas NIMUBONA         
Centre Henri Becquerel Recruiting
Rouen, France
Contact: Hervé TILLY         
Principal Investigator: Hervé TILLY         
Institut de Cancérologie de la Loire Recruiting
Saint Etienne, France, 60008
Contact: Jerôme CORNILLON         
Principal Investigator: Jérôme CORNILLON         
Département d'Hématologie et d'Oncologie, Hôpital CHRU de Hautepierre Not yet recruiting
Strasbourg, France, 67098
Principal Investigator: Bruno LIOURE         
Sub-Investigator: Karin BILGER         
Sub-Investigator: Luc-Matthieu FORNECKER, MD         
Service Hématologie, Hôpital Purpan Not yet recruiting
Toulouse, France, 31059
Principal Investigator: Anne HUYNH         
Sub-Investigator: Murielle ROUSSEL         
CHRU Tours Not yet recruiting
Tours, France, 37000
Contact: Séverine LISSANDRE         
Principal Investigator: Séverine LISSANDRE         
Institut Gustave Roussy Not yet recruiting
Villejuif, France, 94805
Contact: Vincent RIBRAG         
Principal Investigator: Vincent RIBRAG         
Sponsors and Collaborators
University Hospital, Bordeaux
Roche Pharma AG
Investigators
Principal Investigator: Stéphane VIGOUROUX, MD University Hospital, Bordeaux
Study Chair: Adélaïde DOUSSAU, MD University Hospital, Bordeaux
  More Information

Publications:

Responsible Party: University Hospital, Bordeaux
ClinicalTrials.gov Identifier: NCT01208896     History of Changes
Other Study ID Numbers: CHUBX 2009/09
Study First Received: September 23, 2010
Last Updated: August 19, 2014
Health Authority: France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)

Keywords provided by University Hospital, Bordeaux:
Allogeneic hematopoietic stem cell transplantation
Reduced-intensity conditioning
Chemosensitive relapsed follicular lymphoma

Additional relevant MeSH terms:
Lymphoma
Lymphoma, Follicular
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Lymphoma, Non-Hodgkin

ClinicalTrials.gov processed this record on August 26, 2014