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

This study is ongoing, but not recruiting participants.
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, 2016
Last verified: August 2016
  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 ]

Enrollment: 32
Study Start Date: February 2011
Estimated Study Completion Date: October 2017
Estimated Primary Completion Date: October 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   (Adult)
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

Locations
France
Service Hématologie, Hôpital Minjoz
Besançon, France, 25030
Service des maladies du sang - Hôpital Haut-Lévêque - avenue de magellan
Bordeaux - Pessac, France, 33600
Service Hématologie, Hôpital Augustin Morvan
Brest, France, 29609
University Hospital, Caen
Caen, France
Service Hématologie et Thérapie cellulaire, Pavillon Villemin Pasteur, CHU Clermont-Ferrand
Clermont-Ferrand, France, 63000
CHRU Lille
Lille, France, 59037
CHU Limoges
Limoges, France, 87042
APHP Hôpital Saint Louis
Paris, France, 75475
APHP Hôpital Pitié-Salpêtrière
Paris, France, 75651
APHP Hôpital Henri-Mondor
Paris, France, 94010
Service Hématologie Clinique, Hôpital Pontchaillou
Rennes, France, 35033
Centre Henri Becquerel
Rouen, France
Institut de Cancérologie de la Loire
Saint Etienne, France, 60008
Sponsors and Collaborators
University Hospital, Bordeaux
Roche Pharma AG
Investigators
Principal Investigator: Stéphane VIGOUROUX, 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, 2016
Health Authority: France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
Individual Participant Data  
Plan to Share IPD: No

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

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

ClinicalTrials.gov processed this record on September 23, 2016