This trial is active, not recruiting.

Conditions lymphoma, follicular, stem cell transplantation
Treatment reduced_intensity conditioning
Phase phase 2
Sponsor University Hospital, Bordeaux
Collaborator Roche Pharma AG
Start date February 2011
End date October 2017
Trial size 32 participants
Trial identifier NCT01208896, CHUBX 2009/09


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.

United States No locations recruiting
Other countries No locations recruiting

Study Design

Endpoint classification safety/efficacy study
Intervention model single group assignment
Masking open label
Primary purpose treatment
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.

Primary Outcomes

Overall survival
time frame: 2 year

Secondary Outcomes

Toxic mortality
time frame: 2 year
Progression free survival
time frame: 2 year
Incidence of relapse
time frame: 2 year
Grade II-IV acute GVHD incidence
time frame: 2 year
Chronic GVHD incidence
time frame: 2 year
Morbidity and adverse event
time frame: 2 year
Hematologic reconstitution, Immunologic reconstitution, Chimerism
time frame: 2 years

Eligibility Criteria

Male or female participants from 18 years up to 65 years old.

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

Additional Information

Official title Safety and Efficacy of a Strategy of Allogeneic Hematopoietic Stem Cell Transplantation After Reduced-intensity Conditioning for Chemosensitive Relapsed Follicular Lymphoma
Principal investigator Stéphane VIGOUROUX, MD
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.
Trial information was received from ClinicalTrials.gov and was last updated in August 2016.
Information provided to ClinicalTrials.gov by University Hospital, Bordeaux.