BENdamustine at Elevated Dose for Relapsed Follicular Lymphoma in Intensification Therapy and Transplantation (BENEFIT) (BENEFIT)
4 gennaio 2019 aggiornato da: Centre Leon Berard
A Multicenter Phase II Study Evaluating BeEAM (Bendamustine, Etoposide, Cytarabine, Melphalan) Prior to Autologous Stem Cell Transplant for First and Second Chemosensitive Relapses in Patients With Follicular Lymphoma
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).
Panoramica dello studio
Descrizione dettagliata
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.
Tipo di studio
Interventistico
Iscrizione (Effettivo)
21
Fase
- Fase 2
Contatti e Sedi
Questa sezione fornisce i recapiti di coloro che conducono lo studio e informazioni su dove viene condotto lo studio.
Luoghi di studio
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Côte d'Or
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Dijon, Côte d'Or, Francia, 21000
- CHU de Dijon - Hopital le Bocage
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Haute Normandie
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Rouen, Haute Normandie, Francia, 76038
- Centre Henri Becquerel
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Hérault
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Montpellier, Hérault, Francia, 34295
- CHRU de Montpellier, Hôpital Saint-Eloi
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Ile De France
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Paris, Ile De France, Francia, 75743
- APHP Hôpital Necker
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Ile-de-France
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Paris, Ile-de-France, Francia, 75475
- AP-HP Hôpital Saint-Louis
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Ille Et Vilaine
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Rennes, Ille Et Vilaine, Francia, 35033
- CHU de Rennes - Hôpital Pontchaillou
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Isère
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Grenoble, Isère, Francia, 38043
- CHU Grenoble - Hôpital MICHALLON
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Loire Atlantique
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Nantes, Loire Atlantique, Francia, 44093
- CHU de Nantes hotel Dieu
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Meurthe Et Moselle
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Vandoeuvre Lès Nancy, Meurthe Et Moselle, Francia, 54511
- CHU de Nancy
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Nord Pas De Calais
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Lille, Nord Pas De Calais, Francia, 59037
- CHRU de Lille Hopital Claude Huriez
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Rhône
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Lyon, Rhône, Francia, 69473
- Centre Léon Bérard
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Pierre Bénite, Rhône, Francia, 69495
- CHU Lyon Sud
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Val De Marne
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Créteil, Val De Marne, Francia, 94010
- CHU Henri Mondor
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Criteri di partecipazione
I ricercatori cercano persone che corrispondano a una certa descrizione, chiamata criteri di ammissibilità. Alcuni esempi di questi criteri sono le condizioni generali di salute di una persona o trattamenti precedenti.
Criteri di ammissibilità
Età idonea allo studio
Da 18 anni a 65 anni (Adulto, Adulto più anziano)
Accetta volontari sani
No
Sessi ammissibili allo studio
Tutto
Descrizione
INCLUSION CRITERIA:
- 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
- Total bilirubin ≤ 1.5 x ULN
- Cardiac ejection fraction greater than 50% by echocardiogram or multiple gated acquisition scan (MUGA scan)
- Negative serum pregnancy test for women of childbearing potential*
- Pregnancy tests will include a negative serum pregnancy test (with a sensitivity of at least 25 mill-International Unit (mIU)/ml)
Women of childbearing potential* and men must agree to use adequate contraception prior to study entry, for the duration of study participation and until 6 months after the end of treatment
- Female patients who meet at least one of the following criteria are defined as women of non-childbearing potential:
- ≥ 50 years old and naturally amenorrheic for ≥ 1 year
- Permanent premature ovarian failure confirmed by a specialist gynecologist
- Previous bilateral oophorectomy
- XY genotype, Turner's syndrome or uterine agenesis
- Female patients who do not meet at least of the above criteria are defined as women of childbearing potential
- Ability to understand and willingness to sign a written informed consent document
- Covered by a medical insurance
- Signed informed consent
EXCLUSION CRITERIA:
- 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 )
- Pregnant or lactating female
- Abnormalities in cardiac function or clinically significant heart disease such as acute myocardial infarction or unstable angina within 6 months prior to the start of study treatment, heart failure New York Heart Association (NYHA) class III or IV, uncontrolled hypertension or a history of antihypertensive treatment poor compliance, uncontrolled arrhythmias with treatment, except extrasystoles or minor conduction disorders
- Known involvement of the central nervous system by lymphoma
- History of chronic liver disease
- History of hepatic veno-occlusive disease (VOD) or sinusoidal obstruction syndrome (SOS)
- Excessive alcohol use
Piano di studio
Questa sezione fornisce i dettagli del piano di studio, compreso il modo in cui lo studio è progettato e ciò che lo studio sta misurando.
Come è strutturato lo studio?
Dettagli di progettazione
- Scopo principale: Trattamento
- Assegnazione: N / A
- Modello interventistico: Assegnazione di gruppo singolo
- Mascheramento: Nessuno (etichetta aperta)
Armi e interventi
Gruppo di partecipanti / Arm |
Intervento / Trattamento |
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Sperimentale: BeEAM
High Dose Chemotherapy (HDT) containing :
HDT will be followed by an Autologous Stem Cell Transplantation |
High Dose Chemotherapy (HDT) containing :
HDT will be followed by an Autologous Stem Cell Transplantation on D0
Altri nomi:
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Cosa sta misurando lo studio?
Misure di risultato primarie
Misura del risultato |
Misura Descrizione |
Lasso di tempo |
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Event Free Survival rate (EFS)
Lasso di tempo: Evaluated by the time from inclusion to the time of event appearance with a time of observation of 2 years after inclusion
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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
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Evaluated by the time from inclusion to the time of event appearance with a time of observation of 2 years after inclusion
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Misure di risultato secondarie
Misura del risultato |
Misura Descrizione |
Lasso di tempo |
|---|---|---|
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Safety profile of BeEAM
Lasso di tempo: Evaluated all along the 4 years study follow up for each patient
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The safety analyzable population include all patients who received at least one dose of BeEAM regimen
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Evaluated all along the 4 years study follow up for each patient
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Overall Response Rate (ORR) according to Cheson at al. 2007
Lasso di tempo: Evaluated at day 100 after graft
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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 |
Evaluated at day 100 after graft
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Overall Response Rate (ORR) according to Cheson et al. 1999
Lasso di tempo: Evaluated at day 100 after graft
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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 |
Evaluated at day 100 after graft
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Progression Free Survival (PFS)
Lasso di tempo: Evaluated by the time from inclusion to the time of progression with a study duration of 5 years maximum
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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. |
Evaluated by the time from inclusion to the time of progression with a study duration of 5 years maximum
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Overall Survival (OS)
Lasso di tempo: Evaluated by the time from inclusion to the time of death with a study duration of 5 years maximum
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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
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Evaluated by the time from inclusion to the time of death with a study duration of 5 years maximum
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Collaboratori e investigatori
Qui è dove troverai le persone e le organizzazioni coinvolte in questo studio.
Sponsor
Investigatori
- Investigatore principale: Hervé Ghesquières, Dr, Centre Leon Berard, Lyon
Pubblicazioni e link utili
La persona responsabile dell'inserimento delle informazioni sullo studio fornisce volontariamente queste pubblicazioni. Questi possono riguardare qualsiasi cosa relativa allo studio.
Pubblicazioni generali
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- Cheson BD, Pfistner B, Juweid ME, Gascoyne RD, Specht L, Horning SJ, Coiffier B, Fisher RI, Hagenbeek A, Zucca E, Rosen ST, Stroobants S, Lister TA, Hoppe RT, Dreyling M, Tobinai K, Vose JM, Connors JM, Federico M, Diehl V; International Harmonization Project on Lymphoma. Revised response criteria for malignant lymphoma. J Clin Oncol. 2007 Feb 10;25(5):579-86. doi: 10.1200/JCO.2006.09.2403. Epub 2007 Jan 22.
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- Armitage JO, Weisenburger DD. New approach to classifying non-Hodgkin's lymphomas: clinical features of the major histologic subtypes. Non-Hodgkin's Lymphoma Classification Project. J Clin Oncol. 1998 Aug;16(8):2780-95. doi: 10.1200/JCO.1998.16.8.2780.
- Harris NL, Jaffe ES, Diebold J, Flandrin G, Muller-Hermelink HK, Vardiman J, Lister TA, Bloomfield CD. World Health Organization classification of neoplastic diseases of the hematopoietic and lymphoid tissues: report of the Clinical Advisory Committee meeting-Airlie House, Virginia, November 1997. J Clin Oncol. 1999 Dec;17(12):3835-49. doi: 10.1200/JCO.1999.17.12.3835.
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Studiare le date dei record
Queste date tengono traccia dell'avanzamento della registrazione dello studio e dell'invio dei risultati di sintesi a ClinicalTrials.gov. I record degli studi e i risultati riportati vengono esaminati dalla National Library of Medicine (NLM) per assicurarsi che soddisfino specifici standard di controllo della qualità prima di essere pubblicati sul sito Web pubblico.
Studia le date principali
Inizio studio (Effettivo)
9 luglio 2014
Completamento primario (Effettivo)
12 luglio 2018
Completamento dello studio (Effettivo)
12 luglio 2018
Date di iscrizione allo studio
Primo inviato
6 dicembre 2013
Primo inviato che soddisfa i criteri di controllo qualità
10 dicembre 2013
Primo Inserito (Stima)
11 dicembre 2013
Aggiornamenti dei record di studio
Ultimo aggiornamento pubblicato (Effettivo)
8 gennaio 2019
Ultimo aggiornamento inviato che soddisfa i criteri QC
4 gennaio 2019
Ultimo verificato
1 gennaio 2019
Maggiori informazioni
Termini relativi a questo studio
Parole chiave
- Sicurezza
- Linfoma follicolare
- Sopravvivenza libera da progressione
- Tasso di risposta complessivo
- Fase II
- Bendamustine
- Sopravvivenza globale
- Trapianto autologo di cellule staminali
- Chemosensitive relapse
- Chemioterapia ad alte dosi
- BeEAM
- Sopravvivenza senza eventi
- World Health Organization (WHO) 1 grade
- WHO 2 grade
- WHO 3a grade
Termini MeSH pertinenti aggiuntivi
- Malattie del sistema immunitario
- Neoplasie per tipo istologico
- Neoplasie
- Malattie linfoproliferative
- Malattie linfatiche
- Disturbi immunoproliferativi
- Linfoma non Hodgkin
- Linfoma
- Linfoma, follicolare
- Effetti fisiologici delle droghe
- Meccanismi molecolari dell'azione farmacologica
- Agenti antinfettivi
- Agenti antivirali
- Inibitori enzimatici
- Antimetaboliti, Antineoplastici
- Antimetaboliti
- Agenti antineoplastici
- Agenti immunosoppressivi
- Fattori immunologici
- Agenti Antineoplastici, Alchilanti
- Agenti Alchilanti
- Agonisti mieloablativi
- Agenti antineoplastici, fitogenici
- Inibitori della topoisomerasi II
- Inibitori della topoisomerasi
- Etoposide
- Bendamustina cloridrato
- Melfalan
- Citarabina
Altri numeri di identificazione dello studio
- BENEFIT
- 2013-000076-16 (Numero EudraCT)
Piano per i dati dei singoli partecipanti (IPD)
Hai intenzione di condividere i dati dei singoli partecipanti (IPD)?
No
Queste informazioni sono state recuperate direttamente dal sito web clinicaltrials.gov senza alcuna modifica. In caso di richieste di modifica, rimozione o aggiornamento dei dettagli dello studio, contattare register@clinicaltrials.gov. Non appena verrà implementata una modifica su clinicaltrials.gov, questa verrà aggiornata automaticamente anche sul nostro sito web .
Prove cliniche su Linfoma follicolare
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Portola PharmaceuticalsRitiratoAITL | Linfoma periferico a cellule T (PTCL NOS) | Linfomi nodali di T Follicular Helper (TFH) | Linfoma follicolare a cellule T (FTCL) | ALCL | HSTCL | EATL I, II | MEITL, EATL Tipo II | Linfoma nasale
Prove cliniche su BeEAM
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Insel Gruppe AG, University Hospital BernMundipharma Medical CompanySospeso