Lymphoma, Follicular, Stem Cell Transplantation
Conditions
Keywords
Allogeneic hematopoietic stem cell transplantation, Reduced-intensity conditioning, Chemosensitive relapsed follicular lymphoma
Brief 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.
Interventions
DRUGReduced_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.
Sponsors
University Hospital, Bordeaux
Roche Pharma AG
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Overall survival | 2 year |
Secondary
| Measure | Time frame |
|---|---|
| Toxic mortality | 2 year |
| Progression free survival | 2 year |
| Incidence of relapse | 2 year |
| Grade II-IV acute GVHD incidence | 2 year |
| Chronic GVHD incidence | 2 year |
| Morbidity and adverse event | 2 year |
| Hematologic reconstitution, Immunologic reconstitution, Chimerism | 2 years |
Countries
France
Contacts
PRINCIPAL_INVESTIGATORStéphane VIGOUROUX, MD
University Hospital, Bordeaux
Outcome results
None listed