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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01208896
Recruitment Status : Active, not recruiting
First Posted : September 24, 2010
Last Update Posted : August 22, 2016
Roche Pharma AG
Information provided by (Responsible Party):
University Hospital, Bordeaux

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.

Condition or disease Intervention/treatment Phase
Lymphoma, Follicular Stem Cell Transplantation Drug: Reduced_intensity conditioning Phase 2

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.

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 32 participants
Intervention Model: Single Group Assignment
Masking: None (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
Study Start Date : February 2011
Estimated Primary Completion Date : October 2017
Estimated Study Completion Date : October 2017

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Lymphoma

Arm Intervention/treatment
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.

Primary Outcome Measures :
  1. Overall survival [ Time Frame: 2 year ]

Secondary Outcome Measures :
  1. Toxic mortality [ Time Frame: 2 year ]
  2. Progression free survival [ Time Frame: 2 year ]
  3. Incidence of relapse [ Time Frame: 2 year ]
  4. Grade II-IV acute GVHD incidence [ Time Frame: 2 year ]
  5. Chronic GVHD incidence [ Time Frame: 2 year ]
  6. Morbidity and adverse event [ Time Frame: 2 year ]
  7. Hematologic reconstitution, Immunologic reconstitution, Chimerism [ Time Frame: 2 years ]

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Ages Eligible for Study:   18 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01208896

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
Principal Investigator: Stéphane VIGOUROUX, MD University Hospital, Bordeaux


Responsible Party: University Hospital, Bordeaux Identifier: NCT01208896     History of Changes
Other Study ID Numbers: CHUBX 2009/09
First Posted: September 24, 2010    Key Record Dates
Last Update Posted: August 22, 2016
Last Verified: August 2016
Individual Participant Data (IPD) Sharing Statement:
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
Neoplasms by Histologic Type
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Lymphoma, Non-Hodgkin