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Trial record 38 of 1147 for:    "Follicular lymphoma"

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

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ClinicalTrials.gov Identifier: NCT02008006
Recruitment Status : Terminated (Insufficient recruitment and unavailability of the treatment)
First Posted : December 11, 2013
Last Update Posted : January 8, 2019
Sponsor:
Information provided by (Responsible Party):
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).

Condition or disease Intervention/treatment Phase
Follicular Lymphoma Drug: BeEAM Phase 2

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 21 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: 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
Actual Study Start Date : July 9, 2014
Actual Primary Completion Date : July 12, 2018
Actual Study Completion Date : July 12, 2018


Arm Intervention/treatment
Experimental: BeEAM

High Dose Chemotherapy (HDT) containing :

  • Bendamustine
  • Etoposide
  • Cytarabine
  • Melphalan

HDT will be followed by an Autologous Stem Cell Transplantation

Drug: BeEAM

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

Other Names:
  • Bendamustine
  • Etoposide
  • Cytarabine
  • Melphalan




Primary Outcome Measures :
  1. Event Free Survival rate (EFS) [ Time Frame: 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 :
  1. Safety profile of BeEAM [ Time Frame: 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

  2. Overall Response Rate (ORR) according to Cheson at al. 2007 [ Time Frame: 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


  3. Overall Response Rate (ORR) according to Cheson et al. 1999 [ Time Frame: 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


  4. Progression Free Survival (PFS) [ Time Frame: 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.


  5. Overall Survival (OS) [ Time Frame: 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



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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
Criteria

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

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 ClinicalTrials.gov identifier (NCT number): NCT02008006


Locations
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France
CHU de Dijon - Hôpital Le Bocage
Dijon, Côte d'Or, France, 21000
Centre Henri Becquerel
Rouen, Haute Normandie, France, 76038
CHRU de Montpellier, Hôpital Saint-Eloi
Montpellier, Hérault, France, 34295
APHP Hôpital Necker
Paris, Ile De France, France, 75743
AP-HP Hôpital Saint-Louis
Paris, Ile-de-France, France, 75475
CHU de Rennes - Hôpital Pontchaillou
Rennes, Ille Et Vilaine, France, 35033
CHU Grenoble - Hôpital Michallon
Grenoble, Isère, France, 38043
CHU de Nantes Hôtel Dieu
Nantes, Loire Atlantique, France, 44093
CHU de Nancy
Vandoeuvre Lès Nancy, Meurthe Et Moselle, France, 54511
CHRU de Lille Hôpital Claude Huriez
Lille, Nord Pas De Calais, France, 59037
Centre Léon Bérard
Lyon, Rhône, France, 69473
CHU Lyon Sud
Pierre Bénite, Rhône, France, 69495
CHU Henri Mondor
Créteil, Val De Marne, France, 94010
Sponsors and Collaborators
Centre Leon Berard
Investigators
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Principal Investigator: Hervé Ghesquières, Dr Centre Léon Bérard, Lyon

Publications:
Weigert O, Uysal A, Metzner B., et al.: Impact of autologous stem cell transplantation and/or rituximab on outcome of patients with relapsed follicular lymphoma - Retrospective analysis of 2 randomized trials of the German Low Grade Lymphoma Study Group (GLSG). ASH Annual Meeting Abstracts 112:2189, 2008 (abstr)
Fischer K, Stilgenbauer S, Schweighofer CD, et al.: Bendamustine in combination with rituximab (BR) for patients with relapsed chronic lymphocitic leukemia (CLL): a multicenter phase II trial of the German CLL study group. Blood 112, 2008 (abstr)
Rummel M, iederle N, aschmeyer G, et al.: Bendamustine plus rituximab is superior in respect of progression-free survival and CR rate when compared to CHOP plus rituximab as first-line treatment of patients with advanced follicular, indolent, and mantle cell lymphomas: Final results of a randomized phase III study of the StiL (Study Group Indolent Lymphomas, Germany). Lancet. 2013 Feb 19 (In press)

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Responsible Party: Centre Leon Berard
ClinicalTrials.gov Identifier: NCT02008006     History of Changes
Other Study ID Numbers: BENEFIT
2013-000076-16 ( EudraCT Number )
First Posted: December 11, 2013    Key Record Dates
Last Update Posted: January 8, 2019
Last Verified: January 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Keywords provided by Centre Leon Berard:
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
Additional relevant MeSH terms:
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Lymphoma, Follicular
Lymphoma
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Lymphoma, Non-Hodgkin
Cytarabine
Etoposide
Etoposide phosphate
Melphalan
Bendamustine Hydrochloride
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antimetabolites, Antineoplastic
Antimetabolites
Antiviral Agents
Anti-Infective Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antineoplastic Agents, Alkylating
Alkylating Agents
Myeloablative Agonists