Allogeneic Hematopoietic Stem Cell Transplantation After Reduced-intensity Conditioning for Relapsed Follicular Lymphoma
Conditions
Lymphoma, Follicular - Stem Cell Transplantation
Conditions: official terms
Lymphoma - Lymphoma, Follicular
Conditions: Keywords
Allogeneic hematopoietic stem cell transplantation, Reduced-intensity conditioning, Chemosensitive relapsed follicular lymphoma
Study Type
Interventional
Study Phase
Phase 2
Study Design
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Intervention
Name: Reduced_intensity conditioning
Type: Drug
Overall Status
Recruiting
Summary
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.
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.
Criteria for eligibility
Healthy Volunteers: No
Maximum Age: 65 Years
Minimum Age: 18 Years
Gender: Both
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
Locations
University Hospital Angers
Angers Cedex 01, Angers, France
Status: Not yet recruiting
Contact: Martine GARDEMBAS-PAIN, Dr - 02.41.35.47.05 - MaGardembas@chu-angers.fr
Service Hématologie, Hôpital Minjoz
Besançon, France
Status: Not yet recruiting
Service des maladies du sang - Hôpital Haut-Lévêque - avenue de magellan
Bordeaux - Pessac, France
Status: Recruiting
Service Hématologie, Hôpital Augustin Morvan
Brest, France
Status: Recruiting
University Hospital, Caen
Caen, France
Status: Recruiting
Service Hématologie et Thérapie cellulaire, Pavillon Villemin Pasteur, CHU Clermont-Ferrand
Clermont-Ferrand, France
Status: Recruiting
CHU Grenoble
Grenoble, France
Status: Not yet recruiting
Contact: Claude-eric BULABOIS
CHRU Lille
Lille, France
Status: Recruiting
Contact: Ibrahim YAKOUB-AGHA
CHU Limoges
Limoges, France
Status: Recruiting
Contact: Pascal TURLURE
Hôpital Edouard Herriot
Lyon, France
Status: Not yet recruiting
Contact: Mauricette MICHALLET, MD - 04 72 11 74 01 - mauricette.michallet@chu-lyon.fr
Service Hématologie Oncologie, Hôpital Lapeyronie, CHU de Montpellier
Montpellier, France
Status: Not yet recruiting
CHU Nancy
Nancy, France
Status: Not yet recruiting
Contact: Pierre FEUGIER
Service Hématologie Clinique, CHU -Hôtel Dieu
Nantes, France
Status: Not yet recruiting
Service Hématologie Clinique, Hôpital Archet 1
Nice, France
Status: Not yet recruiting
APHP Hôpital Henri-Mondor
Paris, France
Status: Recruiting
Contact: Corinne HAOUIN
APHP Hôpital Necker-Enfants malades
Paris, France
Status: Not yet recruiting
Contact: Agnès BUZYN
APHP Hôpital Pitié-Salpêtrière
Paris, France
Status: Recruiting
Contact: Nathalie DHEDIN
APHP Hôpital Saint Louis
Paris, France
Status: Recruiting
Contact: Gérard SOCIE
CHU Poitiers - La Milétrie
Poitiers, France
Status: Not yet recruiting
Contact: Natacha MAILLARD
Service Hématologie Clinique, Hôpital Pontchaillou
Rennes, France
Status: Recruiting
Centre Henri Becquerel
Rouen, France
Status: Recruiting
Contact: Hervé TILLY
Institut de Cancérologie de la Loire
Saint Etienne, France
Status: Recruiting
Contact: Jerôme CORNILLON
Département d'Hématologie et d'Oncologie, Hôpital CHRU de Hautepierre
Strasbourg, France
Status: Not yet recruiting
Service Hématologie, Hôpital Purpan
Toulouse, France
Status: Not yet recruiting
CHRU Tours
Tours, France
Status: Not yet recruiting
Contact: Séverine LISSANDRE
Institut Gustave Roussy
Villejuif, France
Status: Not yet recruiting
Contact: Vincent RIBRAG
Start Date
February 2011
Completion Date
August 2017
Sponsors
University Hospital, Bordeaux
Source
University Hospital, Bordeaux
Record processing date
ClinicalTrials.gov processed this data on July 28, 2015
ClinicalTrials.gov page