Neoplasms

Blood and Lymph Conditions

Immune System Diseases

All Conditions

Rare Diseases

Lymphoma

Lymphoma, Mantle-Cell

Lymphoma, Follicular

Lymphoma, Large B-Cell, Diffuse

Lymphoma, B-Cell

Neoplasms by Histologic Type

Lymphoproliferative Disorders

Lymphatic Diseases

Immunoproliferative Disorders

Lymphoma, Non-Hodgkin

Lymphosarcoma

Mantle Cell Lymphoma

Follicular Lymphoma

B-cell Lymphoma

Diffuse Large B-Cell Lymphoma

Antineoplastic Agents

All Drugs and Chemicals

Anti-Infective Agents

Etoposide

Cytarabine

Bendamustine Hydrochloride

Melphalan

Etoposide phosphate

Carmustine

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

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

BeEAM

BEAM

Thomas Pabst, Prof Dr. med

Felix Keil, Prim. Univ. Prof. Dr

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.

Background

High-dose chemotherapy (HDCT) followed by autologous stem cell transplantation (ASCT) is considered the treatment of choice for relapsed/refractory lymphomas. On the basis of the results of the PARMA study group trial, high-dose chemotherapy followed by ASCT has become the standard of care for patients with relapsed, chemo-sensitive aggressive lymphoma and it is the treatment of choice in patients relapsing with follicular lymphoma and Hodgkin's disease. The BEAM (BCNU, etoposide, cyclophosphamide, melphalan) chemotherapy regimen is the most frequently used conditioning regimen since more than thirty years. Toxic pneumonia with interstitial infiltration and impairment of the diffusion capacity of the lung is a recognized complication of HDCT regimens containing BCNU. Recently, it has been shown that the EAM regimen (thus omitting BCNU) is not sufficient to obtain equal response rates if compared with BEAM and poorer disease control resulted in impaired disease-free survival (DFS). Thus, it might be detrimental for patients just to eliminate BCNU without an appropriate substitution. Replacing BCNU by Bendamustine with its potential to eradicate residual or treatment-resistant lymphoma cells could be a promising clinical approach and should be investigated in a randomized phase II clinical trial comparing standard BEAM with BeEAM. Bendamustine combines the alkylating activity of the mustard group with the antimetabolite activity of the purine analogue and was studied in several entities of B-cell neoplasms and demonstrated significantly superior efficacy compared with standard therapies in the treatment of relapsed chronic lymphocytic leukemia (CLL) and indolent NHL and myeloma. The BRIGHT study confirmed the non-inferiority of a immunochemo-therapy with Rituximab-Bendamustine when compared with R-CHOP or Rituximab, Cyclophosphamide, Vincristine, Prednisone (R-CVP) in indolent lymphoma or mantle cell lymphoma. Recently, Visani et al have shown that Bendamustine, coupled with fixed doses of Etoposide, Cytarabine, and Melphalan (ie, BeEAM) in the conditioning regimen for ASCT for resistant/relapsed lymphoma (HD and NHL) patients is highly active and resulted in promising results concerning safety and efficacy. No treatment mortality was observed and no relevant pulmonary toxicity was seen. Non-hematological toxicity was moderate, and most prominent toxicities were gastroenteritis grade 3 to 4 in 34% and mucositis grade 3 to 4 in 35%, respectively. No grade 3 to 4 cardiac toxicity or toxic pneumonia was observed. Engraftment was rapid and trilinear, and stable hematopoiesis was observed. BeEAM was very effective, with 81% of patients in complete response after a median observation time of 18 months. A recent update of this study showed that at 41 months still 72% of the patients are still in complete remission and the 3-year performance status (PS) was 75%. Four patients showed a first remission ever with the Bendamustine containing regimen. In 35 patients treated at the Vienna centre according to the Visani BeEAM protocol, these encouraging data of Visani et al could be reproduced; similar toxicities and rapid and stable engraftment were observed. Finally, the combination of Bendamustine with sequential application of high-dose Cytarabine was reported to improve the response rates in relapsing lymphomas. In conclusion, it seems promising to integrate Bendamustine in myeloablative regimens in ASCT, but a randomized clinical trial is lacking so far.

Objective

Replacing the chemotherapeutic drug BCNU by Bendamustine within the four-drug chemotherapy regimen BEAM reduces the occurrence of early and late pulmonary toxicity in lymphoma patients undergoing high-dose chemotherapy with autologous stem cell transplantation. Primary Objective: To show a clinically meaningful reduction of lung toxicity - defined as a a decrease of the diffusion capacity of the lung for carbon monoxide (DLCO) by 20% or more from baseline before ASCT - from 25% of patients in the BEAM group to 4% of patients in the BeEAM group at 3 months after ASCT. Use Dinakara equation for adjusting DLCO for hemoglobin. Secondary Objectives: Acute and late toxicity/adverse events (CTCAE 4.0). Hematologic recovery and engraftment after 3 months. Early and late lung toxicity Cardiac assessment by ECHO/ECG and quality of life before,3 and 12 months after ASCT. Overall survival and progression free survival after 12 months and then yearly as routine follow-up assessments.

Methods

Two high-dose chemotherapy regimens (BeEAM versus BEAM) used for conditioning treatment before autologous stem cell transplantation will be compared in a 1:1 randomization. The experimental arm is the BeEAM regimen. The BEAM regimen is the control treatment. Lung toxicity will be assessed by spiroergometry at the 60% level of maximum exercise capacity, as well as by assessing the diffusion capacity of the lung for carbon monoxide (DLCO). This analysis will be performed before ASCT, as well as 3 months and 12 months after ASCT. Patients will be assessed for cardio-pulmonary toxicity before ASCT, as well as 3 and 12 months after ASCT. Thereafter, patient follow-up will be performed clinically once per year.

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

A Randomized Phase II Trial Comparing BeEAM With BEAM as Conditioning Regimen for Autologous Stem Cell Transplantation (ASCT) in Lymphoma Patients (BEB-trial)

Hanusk Krankenhaus Wien

Insel Gruppe AG, University Hospital Bern

Heart and Blood Diseases

Multiple Myeloma

Neoplasms, Plasma Cell

Hemostatic Disorders

Blood Coagulation Disorders

Vascular Diseases

Paraproteinemias

Blood Protein Disorders

Hematologic Diseases

Hemorrhagic Disorders

Bendaumustine, Etoposide, Cytrabine and Melphalan in autologous transplant for multiple myeloma

Scott R Solomon, MD

High-dose chemotherapy and autologous stem cell transplantation (ASCT) as part of the up-front treatment of patients with multiple myeloma has been associated with improved disease-free and overall survival in multiple large randomized controlled trials. Following 3-6 cycles of standard induction therapy with biologic agents, consolidation with high dose Melphalan and ASCT has become the standard-of-care approach for fit myeloma patients up to 70 years of age. Single-agent high-dose Melphalan (200mg/m2) is currently the standard-of-care preparative regimen prior to autologous transplant in Myeloma. Historical studies utilizing Busulfan- or Total Body Irradiation-based preparative regimens have yielded similar results to single-agent Melphalan with higher toxicity.

Myeloma patients, following up-front induction therapy, will receive an ASCT following a high-dose bendamustine-based preparative regimen (BeEAM). The primary endpoint of this trial will be the rate of CR at day 100 post-transplant. Experience from the literature, as well as results from our institution, suggests that following ASCT for the upfront treatment of myeloma, the rate of CR at day 100 post-transplant is approximately 45%. It is hoped that under this protocol, this rate will be at least 65%. Thus we statistically formalize this study by testing the null hypothesis that p, the CR rate is 0.65 or more versus the alternative hypothesis that p is less than 0.45. A sample size of 65 pts gives 90% power with an alpha=0.05, using the formula for a one sample binomial (two-sided) test of a proportion.

High Dose Chemotherapy Using BeEAM for Autologous Transplant in Multiple Myeloma

A Phase II Trial of High-dose Bendamustine, Etoposide, Cytarabine, and Melphalan (BeEAM) in the Up-front Treatment of Multiple Myeloma

Using IMWG criteria: PR (partial response) noted as \>50% reduction of serum M-protein and reduction in 24hr urinary M-protein by \>90% or to \<200mg/24h; VgPR (very good partial response) noted as serum and urine M-protein detectable by immunofixation but not on electrophoresis or \>90% reduction in serum M-protein plus urine M-protein level \<100mg/24h; CR (complete response) noted as negative immunofixation on the serum and urine and disappearance of any soft tissue plasmacytomas and \<5% plasma cells in bone marrow; sCR (stringent complete response) noted as CR defined above plus normal FLC ratio and absence of clonal cells in bone marrow by immunohistochemistry or immunofluorescence.

Teva Pharmaceuticals USA

Northside Hospital, Inc.

Bendaumustine, Etoposide, Cytrabine and Melphalan in autologous transplant for multiple myeloma

BeEAM: BeEAM

Age, Continuous

Sex: Female, Male

Race (NIH/OMB)

United States

Region of Enrollment

Dr. Scott Solomon

To Estimate the Response at Day 100 Following Transplant (Rate of CR)

Number of Patients With Overall Survival Post-transplant

Number of Patients With Progression-free Survival

Number of Patients Who Relapsed After Transplant

Overall Study

Symptoms and General Pathology

Disease Progression

Enzyme Inhibitors

Antimetabolites

Antiviral Agents

Immunosuppressive Agents

Immunologic Factors

Antineoplastic Agents, Alkylating

Alkylating Agents

High Dose Chemotherapy (HDT) containing :

* Bendamustine
* Etoposide
* Cytarabine
* Melphalan

HDT will be followed by an Autologous Stem Cell Transplantation

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

Hervé Ghesquières, Dr

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).

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.

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

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

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

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

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

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

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.

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

Centre Leon Berard

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
A Trial Comparing the Two High-dose Chemotherapies BeEAM and BEAM Given Before Autologous Stem Cell Transplantation (ASCT) in Lymphoma Patients (BEB-trial)	NCT02278796	Lymphoma, Large... Lymphoma, Folli... Lymphoma, Mantl...	BeEAM BEAM	18 Years - 75 Years	Insel Gruppe AG, University Hospital Bern
High Dose Chemotherapy Using BeEAM for Autologous Transplant in Multiple Myeloma	NCT02416206	Multiple Myelom...	BeEAM	18 Years - 70 Years	Northside Hospital, Inc.
BENdamustine at Elevated Dose for Relapsed Follicular Lymphoma in Intensification Therapy and Transplantation (BENEFIT)	NCT02008006	Follicular Lymp...	BeEAM	18 Years - 65 Years	Centre Leon Berard
BENdamustine at Elevated Dose for Relapsed Follicular Lymphoma in Intensification Therapy and Transplantation (BENEFIT)	NCT02008006	Follicular Lymp...	BeEAM	18 Years - 65 Years	Centre Leon Berard

Spots Global Cancer Trial Database for beeam

Every month we try and update this database with for beeam cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Spots Global Cancer Trial Database for beeam

Every month we try and update this database with for beeam cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for beeam cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.