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Follicular LymphomaPhase 2BENEFITNCT02008006

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

A Phase 2 study testing BeEAM in people with Follicular Lymphoma, run by Centre Leon Berard at 13 sites in France.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial 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). Read more about this study

Who is it for?
Ages 18 to 65 years
Conditions the study is for
Follicular Lymphoma
What is being tested?
BeEAM
Could I receive a placebo?
No, everyone receives an active treatment
How many people
21 participants
Where
13 sitesFrance
Study dates
9 Jul 2014to 12 Jul 2018
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 65 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.
Show all 29Show fewer
  • 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

Who cannot join

  • 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
Show all 21Show fewer
  • 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

Trial locations and contacts

13 sites in 1 country.

13 sites in 1 country

France13 sites

  • CHU Henri Mondor

    Créteil, Val De Marne, 94010

  • CHU de Dijon - Hôpital Le Bocage

    Dijon, Côte d'Or, 21000

  • CHU Grenoble - Hôpital Michallon

    Grenoble, Isère, 38043

  • CHRU de Lille Hôpital Claude Huriez

    Lille, Hauts-de-France, 59037

  • Centre Léon Bérard

    Lyon, Rhône, 69473

  • CHRU de Montpellier, Hôpital Saint-Eloi

    Montpellier, Hérault, 34295

  • CHU de Nantes Hôtel Dieu

    Nantes, Loire Atlantique, 44093

  • AP-HP Hôpital Saint-Louis

    Paris, Île-de-France Region, 75475

  • APHP Hôpital Necker

    Paris, Île-de-France Region, 75743

  • CHU Lyon Sud

    Pierre-Bénite, Rhône, 69495

  • CHU de Rennes - Hôpital Pontchaillou

    Rennes, Ille Et Vilaine, 35033

  • Centre Henri Becquerel

    Rouen, Haute Normandie, 76038

  • CHU de Nancy

    Vandœuvre-lès-Nancy, Meurthe Et Moselle, 54511

Other trials in France

About this study

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

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).

Read the 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.

Being tested
BeEAM
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
Medical subject headings
Lymphoma, Follicular

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • BeEAMDrug

    Also called Bendamustine, Etoposide, Cytarabine, Melphalan

    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

Study groups in NCT02008006
Study groupRoleWhat they receive
BeEAMExperimentalHigh Dose Chemotherapy (HDT) containing : * Bendamustine * Etoposide * Cytarabine * Melphalan HDT will be followed by an Autologous Stem Cell Transplantation
Receives: Drug: BeEAM

What is being measured

The primary outcome is the main question the study is designed to answer.

  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

    Measured: 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)

  1. Safety profile of BeEAM

    The safety analyzable population include all patients who received at least one dose of BeEAM regimen

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

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

    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

    Measured: Evaluated at day 100 after graft

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

    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

    Measured: Evaluated at day 100 after graft

  4. Progression Free Survival (PFS)

    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.

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

  5. Overall Survival (OS)

    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

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

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted11 Dec 2013 (estimated)
  2. Study start9 Jul 2014
  3. Primary completion12 Jul 2018
  4. Study completion12 Jul 2018

Why it stopped: Insufficient recruitment and unavailability of the treatment

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
21 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02008006
Sponsor's protocol ID
BENEFIT
Other IDs
2013-000076-16
Acronym
BENEFIT
Status last verified
Jan 2019
First submitted
6 Dec 2013
Last updated
8 Jan 2019
Results posted
No
Data monitoring committee
Yes
Individual data sharing
No

Publications

  • A clinical evaluation of the International Lymphoma Study Group classification of non-Hodgkin's lymphoma. The Non-Hodgkin's Lymphoma Classification Project. Blood. 1997 Jun 1;89(11):3909-18.

    PubMed 9166827

  • 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.

    PubMed 9704731

  • 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.

    PubMed 10577857

  • Sabattini E, Bacci F, Sagramoso C, Pileri SA. WHO classification of tumours of haematopoietic and lymphoid tissues in 2008: an overview. Pathologica. 2010 Jun;102(3):83-7. No abstract available.

    PubMed 21171509

  • Salles GA. Clinical features, prognosis and treatment of follicular lymphoma. Hematology Am Soc Hematol Educ Program. 2007:216-25. doi: 10.1182/asheducation-2007.1.216.

    PubMed 18024633

  • Ott G, Katzenberger T, Lohr A, Kindelberger S, Rudiger T, Wilhelm M, Kalla J, Rosenwald A, Muller JG, Ott MM, Muller-Hermelink HK. Cytomorphologic, immunohistochemical, and cytogenetic profiles of follicular lymphoma: 2 types of follicular lymphoma grade 3. Blood. 2002 May 15;99(10):3806-12. doi: 10.1182/blood.v99.10.3806.

    PubMed 11986240

  • Freedman AS. Biology and management of histologic transformation of indolent lymphoma. Hematology Am Soc Hematol Educ Program. 2005:314-20. doi: 10.1182/asheducation-2005.1.314.

    PubMed 16304397

  • Montoto S, Fitzgibbon J. Transformation of indolent B-cell lymphomas. J Clin Oncol. 2011 May 10;29(14):1827-34. doi: 10.1200/JCO.2010.32.7577. Epub 2011 Apr 11.

    PubMed 21483014

  • Federico M, Bellei M, Marcheselli L, Luminari S, Lopez-Guillermo A, Vitolo U, Pro B, Pileri S, Pulsoni A, Soubeyran P, Cortelazzo S, Martinelli G, Martelli M, Rigacci L, Arcaini L, Di Raimondo F, Merli F, Sabattini E, McLaughlin P, Solal-Celigny P. Follicular lymphoma international prognostic index 2: a new prognostic index for follicular lymphoma developed by the international follicular lymphoma prognostic factor project. J Clin Oncol. 2009 Sep 20;27(27):4555-62. doi: 10.1200/JCO.2008.21.3991. Epub 2009 Aug 3.

    PubMed 19652063

  • Solal-Celigny P, Roy P, Colombat P, White J, Armitage JO, Arranz-Saez R, Au WY, Bellei M, Brice P, Caballero D, Coiffier B, Conde-Garcia E, Doyen C, Federico M, Fisher RI, Garcia-Conde JF, Guglielmi C, Hagenbeek A, Haioun C, LeBlanc M, Lister AT, Lopez-Guillermo A, McLaughlin P, Milpied N, Morel P, Mounier N, Proctor SJ, Rohatiner A, Smith P, Soubeyran P, Tilly H, Vitolo U, Zinzani PL, Zucca E, Montserrat E. Follicular lymphoma international prognostic index. Blood. 2004 Sep 1;104(5):1258-65. doi: 10.1182/blood-2003-12-4434. Epub 2004 May 4.

    PubMed 15126323

  • Carreras J, Lopez-Guillermo A, Fox BC, Colomo L, Martinez A, Roncador G, Montserrat E, Campo E, Banham AH. High numbers of tumor-infiltrating FOXP3-positive regulatory T cells are associated with improved overall survival in follicular lymphoma. Blood. 2006 Nov 1;108(9):2957-64. doi: 10.1182/blood-2006-04-018218. Epub 2006 Jul 6.

    PubMed 16825494

  • Dave SS, Wright G, Tan B, Rosenwald A, Gascoyne RD, Chan WC, Fisher RI, Braziel RM, Rimsza LM, Grogan TM, Miller TP, LeBlanc M, Greiner TC, Weisenburger DD, Lynch JC, Vose J, Armitage JO, Smeland EB, Kvaloy S, Holte H, Delabie J, Connors JM, Lansdorp PM, Ouyang Q, Lister TA, Davies AJ, Norton AJ, Muller-Hermelink HK, Ott G, Campo E, Montserrat E, Wilson WH, Jaffe ES, Simon R, Yang L, Powell J, Zhao H, Goldschmidt N, Chiorazzi M, Staudt LM. Prediction of survival in follicular lymphoma based on molecular features of tumor-infiltrating immune cells. N Engl J Med. 2004 Nov 18;351(21):2159-69. doi: 10.1056/NEJMoa041869.

    PubMed 15548776

  • Glas AM, Kersten MJ, Delahaye LJ, Witteveen AT, Kibbelaar RE, Velds A, Wessels LF, Joosten P, Kerkhoven RM, Bernards R, van Krieken JH, Kluin PM, van't Veer LJ, de Jong D. Gene expression profiling in follicular lymphoma to assess clinical aggressiveness and to guide the choice of treatment. Blood. 2005 Jan 1;105(1):301-7. doi: 10.1182/blood-2004-06-2298. Epub 2004 Sep 2.

    PubMed 15345589

  • Alvaro T, Lejeune M, Salvado MT, Lopez C, Jaen J, Bosch R, Pons LE. Immunohistochemical patterns of reactive microenvironment are associated with clinicobiologic behavior in follicular lymphoma patients. J Clin Oncol. 2006 Dec 1;24(34):5350-7. doi: 10.1200/JCO.2006.06.4766.

    PubMed 17135637

  • Wahlin BE, Sander B, Christensson B, Kimby E. CD8+ T-cell content in diagnostic lymph nodes measured by flow cytometry is a predictor of survival in follicular lymphoma. Clin Cancer Res. 2007 Jan 15;13(2 Pt 1):388-97. doi: 10.1158/1078-0432.CCR-06-1734.

    PubMed 17255259

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing BeEAM in people with Follicular Lymphoma, run by Centre Leon Berard at 13 sites in France.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 29 inclusion and 21 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 8 Jan 2019. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 13 sites in France. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was stopped early (reason given: Insufficient recruitment and unavailability of the treatment). Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02008006, which also lists 55 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Jan 2019.

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