A Trial Comparing the Two High-dose Chemotherapies BeEAM and BEAM Given Before Autologous Stem Cell Transplantation (ASCT) in Lymphoma Patients (BEB-trial)

NCT02278796 | Completed Phase 2 Results

• 2 other identifiers: BEB-Trial2014-003629-16
• Study Type: interventional
• Target: 108
• Locations: 2 countries
• Sites: 4

Brief Summary

In the treatment of patient with lymphoma the most common high-dose chemotherapy regimen used prior to autologous transplantation (ASCT) is the BEAM regimen. It consists of four chemotherapy drugs together (BCNU, etoposide, cyclophosphamide, melphalan), whose initial letters are grouped together for BEAM regimen. One of the most common organ damage this intensive treatment is caused by the drug BCNU; it involves a lung injury, which manifests itself in the months after ASCT with increasing shortness of breath and cough, and can result in pulmonary fibrosis. The drug bendamustine is used successfully in different lymphoma types, and its efficacy in lymphoma therapy is well documented. Moreover bendamustine doesn't cause lung injury. Initially experience with bendamustine instead of BCNU - in the so-called BeEAM scheme - shows that this scheme is quite effective and well tolerated, without lung injury. In BeEAM scheme therefore bendamustine replace the BCNU, while the other three drugs are administered in the same dosage and order. The aim of the present study conducted at four centers (Bern and Zurich in Switzerland, Vienna and Linz in Austria) is to compare these two high-dose chemotherapy schemas and to show that the BeEAM scheme causes significantly less lung injury than the BEAM regimen.

Conditions

Lymphoma, Large B-Cell, Diffuse; Lymphoma, Follicular; Lymphoma, Mantle-Cell

Keywords

Diffuse large B-cell lymphomas (DLBC); Follicular lymphomas (FL); Mantle cell lymphomas (MCL)

Outcome Measures

Primary Outcomes (1)

• Number of Patients With a Clinically Meaningful Reduction in Lung Toxicity, Defined as a Reduction of the Diffusion Capacity of the Lung for Carbon Monoxide (DLCO) by at Least 20%.

  Number of patients with a clinically meaningful reduction in lung toxicity, defined as a reduction of the diffusion capacity of the lung for carbon monoxide (DLCO) by at least 20%. DLCO measured in mmol/min/kPA

  100 days

Secondary Outcomes (5)

• Acute Toxicity/Adverse Events (CTCAE4)

  ≤ 35 days

• Hematologic Recovery and Engraftment (ANC)

  100 days

• Percentage of Patients With Overall Survival

  1 year

• Late Toxicity/Adverse Events (CTCAE4)

  Continuously up to 1 year

• Hematologic Recovery and Engraftment (PLT)

  100 days

Study Arms (2)

BeEAM

EXPERIMENTAL

Chemotherapy regimen consisting of bendamustine intravenously on days -7 and -6 at 200 mg/m2; cytarabine, 400 mg/m2 intravenously daily from day -5 to day-2; etoposide, 200 mg/m2 intravenously daily from day -5 to day -2; and melphalan, 140 mg/m2 intravenously on day -1 before reinfusion of autologous stem cells

Drug: BeEAM

BEAM

ACTIVE COMPARATOR

Chemotherapy regimen with carmustine (BCNU) 300 mg/m2 on day -6, cytarabine, 400 mg/m2 intravenously daily from day -5 to day-2; etoposide, 200 mg/m2 intravenously daily from day -5 to day -2; and melphalan, 140 mg/m2 intravenously on day -1 before reinfusion of autologous stem cells

Drug: BEAM

Interventions

BeEAM DRUG

Chemotherapy regimen consisting of bendamustine intravenously on days -7 and -6 at 200 mg/m2; cytarabine, 400 mg/m2 intravenously daily from day -5 to day-2; etoposide, 200 mg/m2 intravenously daily from day -5 to day -2; and melphalan, 140 mg/m2 intravenously on day -1 before reinfusion of autologous stem cells

BeEAM

BEAM DRUG

Chemotherapy regimen with carmustine (BCNU) 300 mg/m2 on day -6, cytarabine, 400 mg/m2 intravenously daily from day -5 to day-2; etoposide, 200 mg/m2 intravenously daily from day -5 to day -2; and melphalan, 140 mg/m2 intravenously on day -1 before reinfusion of autologous stem cells

BEAM

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Written Informed Consent
• Chemosensitive diffuse large B-cell lymphomas (DLBCL), follicular lymphomas (FL), and mantle cell lymphomas (MCL) in first or second remission
• Aged between 18 years and 75 years
• Neutrophils ≥ 1000/μl; Platelets ≥ 100 x 109/L

You may not qualify if:

• Acute uncontrolled infection
• Clinically significant concomitant disease states
• Hematopoietic cell transplantation comorbidity index (HCT-CI) \> 5
• Previous or concurrent malignant disease with the exception of basalioma/spinalioma of the skin or early-stage cervix carcinoma
• Known or suspected non-compliance
• Inability to follow the procedures of the study, e.g. due to language problems, psychological disorders, dementia, etc. of the participant
• Major coagulopathy or bleeding disorder
• Major surgery less than 30 days before start of treatment
• Contraindications to the class of drugs under study, known hypersensitivity or allergy to class of drugs or the investigational product
• Women who are pregnant or breast feeding; Women with the intention to become pregnant during the course of the study
• Lack of safe contraception
• Participation in another study with investigational drug within the 30 days preceding and during the present study
• Previous enrolment into the current study
• Enrolment of the investigator, his/her family members, employees and other dependent persons

Sponsors & Collaborators

• Insel Gruppe AG, University Hospital Bern: lead
• Hanusk Krankenhaus Wien: collaborator

Study Sites (4)

Krankenhaus der Elisabethinen Linz

Linz, 4020, Austria

Location

Hanusch Krankenhaus Wien

Vienna, 1140, Austria

Location

Department for Medical Oncology University Hospital/Inselspital

Bern, 3010, Switzerland

Location

Universitätsspital Zürich

Zurich, 8091, Switzerland

Location

Related Publications (6)

• Visani G, Malerba L, Stefani PM, Capria S, Galieni P, Gaudio F, Specchia G, Meloni G, Gherlinzoni F, Giardini C, Falcioni S, Cuberli F, Gobbi M, Sarina B, Santoro A, Ferrara F, Rocchi M, Ocio EM, Caballero MD, Isidori A. BeEAM (bendamustine, etoposide, cytarabine, melphalan) before autologous stem cell transplantation is safe and effective for resistant/relapsed lymphoma patients. Blood. 2011 Sep 22;118(12):3419-25. doi: 10.1182/blood-2011-04-351924. Epub 2011 Aug 3.

  PMID: 21816830 RESULT

• Loke J, Ward J, Mahendra P, Chaganti S, Malladi R. Outcomes of EAM conditioned autologous haematopoietic SCT for lymphoma. A matched pairs retrospective single-centre study analysis. Bone Marrow Transplant. 2013 Nov;48(11):1486-7. doi: 10.1038/bmt.2013.90. Epub 2013 Jun 10. No abstract available.

  PMID: 23749106 RESULT

• Alessandrino EP, Bernasconi P, Colombo A, Caldera D, Martinelli G, Vitulo P, Malcovati L, Nascimbene C, Varettoni M, Volpini E, Klersy C, Bernasconi C. Pulmonary toxicity following carmustine-based preparative regimens and autologous peripheral blood progenitor cell transplantation in hematological malignancies. Bone Marrow Transplant. 2000 Feb;25(3):309-13. doi: 10.1038/sj.bmt.1702154.

  PMID: 10673703 RESULT

• Flinn IW, van der Jagt R, Kahl BS, Wood P, Hawkins TE, Macdonald D, Hertzberg M, Kwan YL, Simpson D, Craig M, Kolibaba K, Issa S, Clementi R, Hallman DM, Munteanu M, Chen L, Burke JM. Randomized trial of bendamustine-rituximab or R-CHOP/R-CVP in first-line treatment of indolent NHL or MCL: the BRIGHT study. Blood. 2014 May 8;123(19):2944-52. doi: 10.1182/blood-2013-11-531327. Epub 2014 Mar 3.

  PMID: 24591201 RESULT

• Philip T, Guglielmi C, Hagenbeek A, Somers R, Van der Lelie H, Bron D, Sonneveld P, Gisselbrecht C, Cahn JY, Harousseau JL, et al. Autologous bone marrow transplantation as compared with salvage chemotherapy in relapses of chemotherapy-sensitive non-Hodgkin's lymphoma. N Engl J Med. 1995 Dec 7;333(23):1540-5. doi: 10.1056/NEJM199512073332305.

  PMID: 7477169 RESULT

• Keil F, Muller AMS, Berghold A, Riedl R, Buxhofer-Ausch V, Schuster J, Vorburger C, Bohm A, Panny M, Nosslinger T, Greil R, Samaras P, Bencker C, Rutti M, Pabst T. BendaEAM versus BEAM as conditioning regimen for ASCT in patients with relapsed lymphoma (BEB): a multicentre, randomised, phase 2 trial. EClinicalMedicine. 2023 Nov 19;66:102318. doi: 10.1016/j.eclinm.2023.102318. eCollection 2023 Dec.

  PMID: 38024477 DERIVED

MeSH Terms

Conditions

Lymphoma, Large B-Cell, Diffuse; Lymphoma, Follicular; Lymphoma, Mantle-Cell; Dendritic Cell Sarcoma, Interdigitating

Condition Hierarchy (Ancestors)

Lymphoma, B-Cell; Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Histiocytic Disorders, Malignant; Histiocytosis

Results Point of Contact

• Title: Thomas Pabst, Prof Dr. med
• Organization: Inselspital University Hospital Bern

thomas.pabst@insel.ch

+41 31 632 84 30

Study Officials

• Thomas Pabst, Prof Dr. med

  Department for Medical Oncology University Hospital/Inselspital

  STUDY CHAIR

• Felix Keil, Prim. Univ. Prof. Dr

  Hanusch Krankenhaus Wien

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

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

Study Record Dates

• First Submitted: October 15, 2014
• First Posted: October 30, 2014
• Study Start: April 1, 2015
• Primary Completion: November 28, 2018
• Study Completion: November 1, 2020
• Last Updated: August 1, 2025
• Results First Posted: August 1, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will share

Locations

CH (2); AU (2)