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

NCT02008006 | Terminated Phase 2 DMC

• 2 other identifiers: BENEFIT2013-000076-16
• Study Type: interventional
• Target: 21
• Locations: 1 country
• Sites: 13

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).

Conditions

Follicular Lymphoma

Keywords

Follicular Lymphoma; Chemosensitive relapse; High Dose Chemotherapy; Bendamustine; BeEAM; Autologous Stem Cell Transplantation; Safety; Event Free Survival; Overall Response Rate; Progression Free Survival; Overall Survival; Phase II; World Health Organization (WHO) 1 grade; WHO 2 grade; WHO 3a grade

Outcome Measures

Primary Outcomes (1)

• Event Free Survival rate (EFS)

  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

  Evaluated by the time from inclusion to the time of event appearance with a time of observation of 2 years after inclusion

Secondary Outcomes (5)

• Safety profile of BeEAM

  Evaluated all along the 4 years study follow up for each patient

• Overall Response Rate (ORR) according to Cheson at al. 2007

  Evaluated at day 100 after graft

• Overall Response Rate (ORR) according to Cheson et al. 1999

  Evaluated at day 100 after graft

• Progression Free Survival (PFS)

  Evaluated by the time from inclusion to the time of progression with a study duration of 5 years maximum

• Overall Survival (OS)

  Evaluated by the time from inclusion to the time of death with a study duration of 5 years maximum

Study Arms (1)

BeEAM

EXPERIMENTAL

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

Drug: BeEAM

Interventions

BeEAM DRUG

High Dose Chemotherapy (HDT) containing : * Bendamustine 160 mg/m2 for 2 days (D-8 and D-7) * Etoposide 200 mg/m2 and Cytarabine 400 mg/m2 for 4 days (D-6 to D-3) * Melphalan 140 mg/m2 on D-2 HDT will be followed by an Autologous Stem Cell Transplantation on D0

Also known as: Bendamustine, Etoposide, Cytarabine, Melphalan

BeEAM

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically confirmed follicular lymphoma relapsed (WHO grade 1, 2, 3a)
• Patients aged from 18 to 65 years
• First or second chemosensitive relapses after salvage therapy (rituximab-chemotherapy) based on 2007 Cheson et al. international response criteria (CR and PR) before the decision of BeEAM (HDT) and ASCT (autologous stem cell transplantation) treatment
• Eligible for ASCT
• Autologous graft with a minimum of a number of cluster of differentiation 34 (CD34+) cells 3.0x106/kg.
• Autologous transplantation will be performed in hematopoietic stem cell transplantation authorized centers.
• Eastern Cooperative Oncology Group Performance Status (ECOG PS) 0 to 2
• Minimum life expectancy of 3 months
• Cardiovascular baseline corrected QT interval F ( QTcF) ≤ 450 msec (male) or 470 msec (female)
• Medications that may cause corrected QT interval (QTc) interval prolongation should be avoided by patients entering on trial
• Normal organ and marrow function as defined below:
• Absolute neutrophil count ≥ 1.5 G/l
• Platelet count ≥ 100 G/l or \> 75 G/l if the bone marrow is involved
• Creatine clearance ≥ 50 ml/min
• Serum Glutamate Oxaloacetate Transaminase (SGOT) and Serum Glutamate Pyruvate Transaminase (SGPT) ≤ 2.5 x Upper Limit of Normal (ULN) or ≤ 5 x ULN if liver metastasis

You may not qualify if:

• Transformed follicular lymphoma
• Prior autologous or allogeneic transplantation
• Presence of a none chemosensitive disease before HDT according to 2007 Cheson et al. international response criteria (stable or progressive disease)
• Contraindication to any drug contained in the chemotherapy regimens
• Bone marrow infiltration \> 25% before HDT+ASCT
• Positive HIV, Hepatitis C Virus (HCV) and Hepatitis B (HBs)Ag serologies
• Current bacterial, viral or fungal infection
• Treatment with any investigational drug within 30 days before enrolment
• Major surgery within 30 days before enrolment
• Participation in another clinical trial within 30 days prior to enrolment in the study and during study
• Any serious active disease or co-morbid medical conditions that would interfere with therapy
• Prior history of malignancies other than lymphoma (except for basal cell or squamous cell carcinoma of the skin or carcinoma in situ of the cervix or breast) unless the subject has been free of the disease for ≥ 5 years
• Known or suspected hypersensitivity to any of the agents or excipients of the regime under evaluation
• Concomitant treatment with chemotherapy or immunotherapy or radiotherapy
• Yellow fever vaccination (attenuated virus vaccine )

Sponsors & Collaborators

• Centre Leon Berard: lead

Study Sites (13)

CHU de Dijon - Hôpital Le Bocage

Dijon, Côte d'Or, 21000, France

Location

Centre Henri Becquerel

Rouen, Haute Normandie, 76038, France

Location

CHRU de Lille Hôpital Claude Huriez

Lille, Hauts-de-France, 59037, France

Location

CHRU de Montpellier, Hôpital Saint-Eloi

Montpellier, Hérault, 34295, France

Location

CHU de Rennes - Hôpital Pontchaillou

Rennes, Ille Et Vilaine, 35033, France

Location

CHU Grenoble - Hôpital Michallon

Grenoble, Isère, 38043, France

Location

CHU de Nantes Hôtel Dieu

Nantes, Loire Atlantique, 44093, France

Location

CHU de Nancy

Vandœuvre-lès-Nancy, Meurthe Et Moselle, 54511, France

Location

Centre Léon Bérard

Lyon, Rhône, 69473, France

Location

CHU Lyon Sud

Pierre-Bénite, Rhône, 69495, France

Location

CHU Henri Mondor

Créteil, Val De Marne, 94010, France

Location

AP-HP Hôpital Saint-Louis

Paris, Île-de-France Region, 75475, France

Location

APHP Hôpital Necker

Paris, Île-de-France Region, 75743, France

Location

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MeSH Terms

Conditions

Lymphoma, Follicular

Interventions

Bendamustine Hydrochloride; Etoposide; Cytarabine; Melphalan

Condition Hierarchy (Ancestors)

Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Butyrates; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Benzimidazoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Podophyllotoxin; Tetrahydronaphthalenes; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Polycyclic Compounds; Glucosides; Glycosides; Carbohydrates; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Arabinonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Phenylalanine; Amino Acids, Aromatic; Amino Acids, Cyclic; Amino Acids; Amino Acids, Peptides, and Proteins

Study Officials

• Hervé Ghesquières, Dr

  Centre Léon Bérard, Lyon

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 6, 2013
• First Posted: December 11, 2013
• Study Start: July 9, 2014
• Primary Completion: July 12, 2018
• Study Completion: July 12, 2018
• Last Updated: January 8, 2019

Record last verified: 2019-01

Data Sharing

• IPD Sharing: Will not share

Locations

FR (13)