BENdamustine at Elevated Dose for Relapsed Follicular Lymphoma in Intensification Therapy and Transplantation (BENEFIT)

Phase 2

Terminated

• Conditions: Follicular Lymphoma
• Interventions: Drug: BeEAM

• Registration Number: NCT02008006
• Lead Sponsor: Centre Leon Berard

Brief Summary

The purpose of this study is to evaluate the efficacy and safety of BeEAM (bendamustine, etoposide, cytarabine and melphalan) regimen prior to autologous stem cell transplant for first and second chemosensitive relapses in patients with follicular lymphoma (World Health Organisation (WHO) grade 1, 2, 3a).

Detailed Description

The natural history of this follicular lymphoma (FL) is marked by multiple relapses. The prognosis of FL has improved with the use of effective sequential chemotherapy and the introduction of anti-cluster of differentiation antigen 20 (anti-CD20) monoclonal antibody. Based on the multiple phases II, high dose chemotherapy (HDT) followed by autologous stem cell transplantation (ASCT) appear to be an effective treatment in relapsed FL. At rituximab era, the 3-years EFS rate was 75% for relapsed transplanted patients treated in first line therapy in FL2000 protocol. Bendamustine that combines alkylating and antimetabolite activities had proven clinical activity in relapse and in first line therapy of FL. Carmustine (BCNU), etoposide, cytarabine, and melphalan (BEAM regimen) is one of the most used schedule of HDT in non hodgkin lymphoma. Regarding the good safety profile of Bendamustine, Visani et al. proposed a phase I/II of bendamustine at day -7 and -6, followed by etoposide, cytarabine and melphalan with similar dose than BEAM regimen. The bendamustine maximal dose is 200 mg/m² day -7, -6. Data from engraftment showed closed results than those observed after BEAM. None of patients experienced a dose limiting toxicity. In this context, the investigators proposed to perform a multicentric phase II of this regimen with 200 mg/m² day-7 and -6 of bendamustine for first and second relapsed FL with a chemosensitive disease after salvage therapy. No FL was evaluated in Visani et al. study. In addition, the investigators can observe a shortage of the BCNU these last years that incline to evaluate new schedule of HDT.

Study Timeline

• Study First Submitted: 2013-12-06
• Study First Submitted QC: 2013-12-10
• Study First Posted: 2013-12-11
• Study Start: 2014-07-09
• Primary Completion: 2018-07-12
• Study Completion: 2018-07-12
• Status Verified: 2019-01
• Last Update Submitted: 2019-01-04
• Last Update Posted: 2019-01-08

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 21

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
BeEAM	BeEAM	High Dose Chemotherapy (HDT) containing : * Bendamustine * Etoposide * Cytarabine * Melphalan HDT will be followed by an Autologous Stem Cell Transplantation

Primary Outcome Measures

Name	Time	Method
Event Free Survival rate (EFS)	Evaluated by the time from inclusion to the time of event appearance with a time of observation of 2 years after inclusion	EFS will be measured from the date of inclusion to the date of event defined as : death due to any cause, relapse/progression, or changes in therapies. Patients with no event at the time of analysis will be censored at the date of the last contact

Secondary Outcome Measures

Name	Time	Method
Safety profile of BeEAM	Evaluated all along the 4 years study follow up for each patient	The safety analyzable population include all patients who received at least one dose of BeEAM regimen
Overall Response Rate (ORR) according to Cheson at al. 2007	Evaluated at day 100 after graft	ORR is defined by the rate of patients in Complete Response (CR) and in Partial Response (PR) at time of evaluation.; ORR is assessed according to Cheson et al. 2007 criteria
Overall Response Rate (ORR) according to Cheson et al. 1999	Evaluated at day 100 after graft	ORR is defined by the rate of patients in Complete Response (CR) and in Partial Response (PR) at time of evaluation.; ORR assessed according to Cheson et al. 1999 criteria
Overall Survival (OS)	Evaluated by the time from inclusion to the time of death with a study duration of 5 years maximum	OS will be measured from the date of inclusion to the date of death due to any cause and will be censored at the date of last contact for the patients alive at last contact
Progression Free Survival (PFS)	Evaluated by the time from inclusion to the time of progression with a study duration of 5 years maximum	PFS will be measured from the date of inclusion to the date of event defined as : progression/relapse or death due to any cause. Patients with no event at the time of analysis will be censored at the date of the last contact.; PFS will be assessed among all included patients and in the subgroup of complete responders at the beginning of HDT.

Trial Locations

Locations (13)

CHU de Dijon - Hôpital Le Bocage; 🇫🇷 Dijon, Côte d'Or, France

CHRU de Montpellier, Hôpital Saint-Eloi; 🇫🇷 Montpellier, Hérault, France

CHU Grenoble - Hôpital Michallon; 🇫🇷 Grenoble, Isère, France

CHU de Nancy; 🇫🇷 Vandoeuvre Lès Nancy, Meurthe Et Moselle, France

APHP Hôpital Necker; 🇫🇷 Paris, Ile De France, France

Centre Léon Bérard; 🇫🇷 Lyon, Rhône, France

AP-HP Hôpital Saint-Louis; 🇫🇷 Paris, Ile-de-France, France

CHU de Rennes - Hôpital Pontchaillou; 🇫🇷 Rennes, Ille Et Vilaine, France

CHU de Nantes Hôtel Dieu; 🇫🇷 Nantes, Loire Atlantique, France

CHRU de Lille Hôpital Claude Huriez; 🇫🇷 Lille, Nord Pas De Calais, France

CHU Lyon Sud; 🇫🇷 Pierre Bénite, Rhône, France

CHU Henri Mondor; 🇫🇷 Créteil, Val De Marne, France

Centre Henri Becquerel; 🇫🇷 Rouen, Haute Normandie, France