BendamustinePhase 2BeEAM2010-01NCT01296256
Bendamustine, Cytarabine, Etoposide and Melphalan (BeEAM) as Conditioning for Autologous Stem Cell Transplant (ASCT) in Aggressive Non Hodgkin's Lymphoma (NHL).
A Phase 2 study testing Bendamustine-EAM in people with Bendamustine and Conditioning Therapy, run by Grupo Español de Linfomas y Transplante Autólogo de Médula Ósea at 21 sites in Spain.
Trial summary
The purpose of this study is to determine whether Bendamustine in combination with Etoposide, Cytarabine and Melphalan (BeEAM) are effective as conditioning followed by ASCT in patients with aggressive lymphoma. Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Bendamustine, Conditioning Therapy, Autologous Stem Cell Transplant
- What is being tested?
- Bendamustine-EAM
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 60 participants
- Where
- 21 sitesSpain
- Study dates
- May 2011to Nov 2015
- 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 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients being able to meet all requirements of the clinical trial, according to the investigator's criteria,
- Patient giving voluntarily written informed consent before performing any essay test that is not part of routine care of patients.
- Age >o=18 years and >0=70 years
- Candidate for chemotherapy (QT) at high doses and ASCT
- Histologically confirmed aNHL:
- Patients with DLBCL or grade 3 b Follicular lymphoma or PTCL (including anaplastic ALK +) in sensitive relapse, so, in second complete or partial response, after a minimum of 2 cycles of the rescue regimen.
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- Patients with DLBCL or grade 3 b Follicular lymphoma or PTCL (including anaplastic ALK +) in first complete or partial response, if more than one treatment line have been required to reach this first complete or partial response.
- Transformed B cell lymphoma in first CR
- Patients with PTCL (other than anaplastic ALK +) in first CR
- Performance status (ECOG) <0=2.
- Adequate renal, hepatic, and bone marrow function (assessed < 14 days before initiation of the study treatment):
- Neutrophil count <o=1.5 x 109/L
- Platelet count <o=100 x 109/L
- Haemoglobin <o=8.0 g/dL
- Creatinine serum >o=1,5 x ULN mg/dl
- Serum bilirubin <o=1.5 x ULN and alkaline phosphatase <o=2.5 x ULN
- AST, ALT <o=2.5 x ULN (<o=5 x ULN in case of liver metastasis).
- Adequate pulmonary function: forced expiratory volume at 1 second > 65% of predicted or a diffusing capacity of the lung for CO >o=50%.
- Cardiac ejection fraction or greater than 50% by echocardiogram or FEVI.
- A woman capable of gestation (see definition below) should:
- Have two medically supervised negative pregnancy test (minimum sensitivity of 25 mIU / ml) before starting study therapy (the first pregnancy test should be completed in 10 to 14 days prior to initiating bendamustine and the latter pregnancy test 24 hours before the start of this drug).
- Commit to a continued abstinence of heterosexual relationship or agree to use reliable contraception without interruption, 28 days before starting the study therapy, during the study therapy and for 28 days after stopping therapy study.
- A woman capable of gestation is defined as sexually mature woman who:
- has not undergone hysterectomy or bilateral oophorectomy and
- is not naturally postmenopausal (amenorrhea as a result of cancer treatment does not rule the reproductive potential) for at least 24 consecutive months (i.e., menses at any time during the previous 24 consecutive months).
Who cannot join
- Impossibility of collecting, via apheresis, a number of CD34+ cells >o=2 x 106/kg
- To receive any of the following treatments in the 28 days before the start the study treatment:
- i.chemotherapeutic or antitumor agents ii.radiation therapy, except in limited fields, to a maximum dose of <o=10 Gy to control serious life-threatening symptoms iii.glucocorticoids, except doses equivalent to <o=1 mg / kg of prednisolone / day with a duration <o=7 days iv.any therapeutic agent under investigation.
- Known involvement of the central nervous system (CNS) by lymphoma
- 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 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.
- Other serious or uncontrolled medical condition, such as uncontrolled diabetes, uncontrolled active infection, significant cerebrovascular disease or poorly controlled psychiatric disease.
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- Known or suspected hypersensitivity to any of the agents or excipients of the regime under evaluation.
- Presence of any limitations that compromise the patient's ability to comply with the study treatment.
- Positive serology for HIV, HCV or HBV surface antigen (HBsAg). If the HBsAg is negative but anti-core antibodies (HBcAb) are positive and antibody against surface antigen (HBsAb) are negative, there will be a HBV DNA test; If positive results the patient may not be included in the trial. If both types of antibodies HBcAb and HBsAb are positive (indicative of past infection), the patient may be included in the study.
- Previous history of malignancies other than lymphoma (except basal cell or squamous cell skin carcinoma and carcinoma in situ of the cervix or breast) unless the patient is free of disease beyond 5 years.
- Major surgery procedure within 30 days prior to entering this study.
- Pregnant or nursing females.
Trial locations and contacts
21 sites in 1 country.
21 sites in 1 country
Spain21 sites
Hospital Vall d´Hebron
Barcelona, Barcelona, 08035
Hospital Clinic i Provincial
Barcelona, Barcelona, 08036
H. de la Santa Creu i Sant Pau
Barcelona, Barcelona
Hospital Universitario Virgen de Arrixaca
El Palmar, Murcia, 30120
Hospital de Jerez
Jerez de la Frontera, Cádiz, 11407
H.U. 12 de Octubre,
Madrid, Madrid
H.U. Gregorio Marañón,
Madrid, Madrid
H.U. La Paz
Madrid, Madrid
H.U. La Princesa
Madrid, Madrid
Hospital Ramon y Cajal
Madrid, Madrid
Hospital Central de Asturias
Oviedo, Principality of Asturias, 33006
Hospital Son Llátzer
Palma de Mallorca, Mallorca, 07198
Clinica Universitaria de Navarra
Pamplona, Navarre
H. Clínico Universitario de Salamanca
Salamanca, Salamanca
Hospital Universitario de Canarias
Santa Cruz de Tenerife, Tenerife
H. U. Marqués de Valdecilla.
Santander, Cantabria
Complejo Hospitalario Universitario de Santiago
Santiago, A Coruña, 15706
Hospital Clinico de Valencia
Valencia, Valencia, 46010
Hospital Arnau de Vilanova
Valencia, Valencia, 46015
H. La Fe
Valencia, Valencia
Hospital Clínico Lozano Blesa
Zaragoza, Zaragoza, 50009
About this study
Official title: Bendamustine, Cytarabine, Etoposide and Melphalan as Conditioning for Autologous Stem Cell Transplant in Patients With Aggressive Non Hodgkin's Lymphoma.
The purpose of this study is to determine whether Bendamustine in combination with Etoposide, Cytarabine and Melphalan (BeEAM) are effective as conditioning followed by ASCT in patients with aggressive lymphoma.
Read the detailed description
BCNU (carmustine is a nitrosurea alkylating agent used for many years in the conditioning of patients with lymphoma however this drug is hardly available in some countries in Europe, moreover to improve conditioning regimens in autologous stem cell transplant is important because the anti-tumoral effect of high dose therapy are responsible for this procedure efficacy. Although for many years few advances have been achieved in this area now new drugs can be tested in these patients.
Bendamustine is a unique cytotoxic agent with structural similarities to alkylating agents and antimetabolites, but which is non-cross-resistant with alkylating agents and other drugs in vitro and in the clinic. Early clinical studies conducted in the German Democratic Republic more than 30 years ago suggested promising activity in indolent non-Hodgkin's lymphoma (NHL). Two North American trials reported responses in more than 70% of patients with chemotherapy- and rituximab-refractory disease, suggesting that bendamustine may be the most effective drug available for this patient population. Response rates of 90% to 92%, with complete remission in 55% to 60%, have been reported in patients with follicular and mantle-cell lymphoma with the combination of bendamustine and rituximab.(Cheson 2009) Leone et all have recently reported results on the characterization of the mechanisms of action of bendamustine and its comparison with structurally related compounds as chlorambucil and phosphoramide mustard have demonstrated that bendamustine displays a distinct mechanisms of action including activation of DNA-damage stress response and apoptosis, inhibition of mitotic checkpoints, and induction of mitotic catastrophe. Also bendamustine activates a base excision DNA repair pathway rather than an alkyltransferase DNA repair mechanism.
These data suggest that bendamustine possesses mechanistic features that differentiate it from other alkylating agents and makes this old new drug an attractive one to combine with other agents in the conditioning transplant setting (Leone 2008).
- Conditions
- Bendamustine, Conditioning Therapy, Autologous Stem Cell Transplant, Aggressive Non Hodgkin's Lymphoma
- Being tested
- Bendamustine-EAM
- Keywords
- Bendamustine, Conditioning Therapy, Autologous Stem Cell Transplant, Aggressive Non Hodgkin's Lymphoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Bendamustine-EAMDrug
Bendamustine 200 mg/m2 starting dose on day -7 and -6 Etoposide 200 mg/m2 from day -5 to day -2 Ara-C 400 mg/m2 from day -5 to day -2 Melphalan 140 mg/m2 on day -1
| Study group | Role | What they receive |
|---|---|---|
| Bendamustine-EAM | Experimental | Not described Receives: Drug: Bendamustine-EAM |
What is being measured
The primary outcome is the main question the study is designed to answer.
Evaluate the progression free survival using techniques of image (PET and TC)of Bendamustine in combination with Etoposide, Cytarabine and Melphalan (BeEAM) as conditioning followed by ASCT in patients with aggressive lymphoma.
Measured: 18 months follow-up
Secondary outcomes (1)
Evaluate safety BeEAM chemotherapy followed of reinfusion of autologous hematopoietic stem cells by considering the incidence of adverse event (with CTCAE).Evaluate % patients in CR.Evaluate response of ASCT using PET, TC.Evaluate overall survival
Measured: 18 months follow-up
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Feb 2011 (estimated)
- Study startMay 2011
- Primary completionNov 2015
- Study completionNov 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for BendamustineStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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
- 60 participants (actual)
Sponsor and investigators
- Lead sponsor
- Grupo Español de Linfomas y Transplante Autólogo de Médula Ósea
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Mª Dolores Caballero, MD, Principal investigator, University of SalamancaAlejandro Martín, MD, Principal investigator, University of SalamancaJavier Briones, MD, Principal investigator, Fundació Institut de Recerca de l'Hospital de la Santa Creu i Sant PauJuan Manuel Sancho, MD, Principal investigator, Germans Trias i Pujol HospitalCristina Barrenetxea, MD, Principal investigator, Hospital Vall d'HebrónJavier López, MD, Principal investigator, Hospital Universitario Ramon y CajalMª José Rodríguez, MD, Principal investigator, Hospital Universitario de CanariasJorge Gayoso, MD, Principal investigator, Gregorio Marañón Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01296256
- Sponsor's protocol ID
- Benda-EAM2010-01
- Other IDs
- 2010-020926-17
- Acronym
- BeEAM2010-01
- Status last verified
- Feb 2016
- First submitted
- 13 Feb 2011
- Last updated
- 17 Feb 2016
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 17 Feb 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Bendamustine, Cytarabine, Etoposide and Melphalan as Conditioning for Autologous Stem Cell Transplant in Patients With Aggressive Non Hodgkin's Lymphoma.
- ClinicalTrials.gov ID
- NCT01296256
- Acronym / sponsor ID
- BeEAM2010-01 / Benda-EAM2010-01
- Conditions
- Bendamustine, Conditioning Therapy, Autologous Stem Cell Transplant, Aggressive Non Hodgkin's Lymphoma
- Keywords
- Bendamustine, Conditioning Therapy, Autologous Stem Cell Transplant, Aggressive Non Hodgkin's Lymphoma
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 60 participants (actual)
- Lead sponsor
- Grupo Español de Linfomas y Transplante Autólogo de Médula ÓseaUniversity, hospital or other
- Study start
- May 2011
- Primary completion
- Nov 2015 (actual)
- Study completion
- Nov 2015 (actual)
- First posted
- 15 Feb 2011 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to determine whether Bendamustine in combination with Etoposide, Cytarabine and Melphalan (BeEAM) are effective as conditioning followed by ASCT in patients with aggressive lymphoma.
Detailed description
BCNU (carmustine is a nitrosurea alkylating agent used for many years in the conditioning of patients with lymphoma however this drug is hardly available in some countries in Europe, moreover to improve conditioning regimens in autologous stem cell transplant is important because the anti-tumoral effect of high dose therapy are responsible for this procedure efficacy. Although for many years few advances have been achieved in this area now new drugs can be tested in these patients.
Bendamustine is a unique cytotoxic agent with structural similarities to alkylating agents and antimetabolites, but which is non-cross-resistant with alkylating agents and other drugs in vitro and in the clinic. Early clinical studies conducted in the German Democratic Republic more than 30 years ago suggested promising activity in indolent non-Hodgkin's lymphoma (NHL). Two North American trials reported responses in more than 70% of patients with chemotherapy- and rituximab-refractory disease, suggesting that bendamustine may be the most effective drug available for this patient population. Response rates of 90% to 92%, with complete remission in 55% to 60%, have been reported in patients with follicular and mantle-cell lymphoma with the combination of bendamustine and rituximab.(Cheson 2009) Leone et all have recently reported results on the characterization of the mechanisms of action of bendamustine and its comparison with structurally related compounds as chlorambucil and phosphoramide mustard have demonstrated that bendamustine displays a distinct mechanisms of action including activation of DNA-damage stress response and apoptosis, inhibition of mitotic checkpoints, and induction of mitotic catastrophe. Also bendamustine activates a base excision DNA repair pathway rather than an alkyltransferase DNA repair mechanism.
These data suggest that bendamustine possesses mechanistic features that differentiate it from other alkylating agents and makes this old new drug an attractive one to combine with other agents in the conditioning transplant setting (Leone 2008).
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Bendamustine-EAM | Experimental | Drug: Bendamustine-EAM |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (25 listed)
- Patients being able to meet all requirements of the clinical trial, according to the investigator's criteria,
- Patient giving voluntarily written informed consent before performing any essay test that is not part of routine care of patients.
- Age >o=18 years and >0=70 years
- Candidate for chemotherapy (QT) at high doses and ASCT
- Performance status (ECOG) <0=2.
Key exclusion criteria (12 listed)
- Impossibility of collecting, via apheresis, a number of CD34+ cells >o=2 x 106/kg
- To receive any of the following treatments in the 28 days before the start the study treatment:
- i.chemotherapeutic or antitumor agents ii.radiation therapy, except in limited fields, to a maximum dose of <o=10 Gy to control serious life-threatening symptoms iii.glucocorticoids, except doses equivalent to <o=1 mg / kg of prednisolone / day with a duration <o=7 days iv.any therapeutic agent under investigation.
- Known involvement of the central nervous system (CNS) by lymphoma
- 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 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Bendamustine-EAMBendamustine 200 mg/m2 starting dose on day -7 and -6 Etoposide 200 mg/m2 from day -5 to day -2 Ara-C 400 mg/m2 from day -5 to day -2 Melphalan 140 mg/m2 on day -1 | Drug | Bendamustine-EAM |
Primary outcome
Evaluate the progression free survival using techniques of image (PET and TC)of Bendamustine in combination with Etoposide, Cytarabine and Melphalan (BeEAM) as conditioning followed by ASCT in patients with aggressive lymphoma.
Time frame: 18 months follow-up
1 secondary outcome
Evaluate safety BeEAM chemotherapy followed of reinfusion of autologous hematopoietic stem cells by considering the incidence of adverse event (with CTCAE).Evaluate % patients in CR.Evaluate response of ASCT using PET, TC.Evaluate overall survival
Time frame: 18 months follow-up
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Feb 2016.
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Mª Dolores Caballero, MD principal investigator
University of Salamanca
Alejandro Martín, MD principal investigator
University of Salamanca
Javier Briones, MD principal investigator
Fundació Institut de Recerca de l'Hospital de la Santa Creu i Sant Pau
21 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Bendamustine-EAM in people with Bendamustine and Conditioning Therapy, run by Grupo Español de Linfomas y Transplante Autólogo de Médula Ósea at 21 sites in Spain.
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 25 inclusion and 12 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: finished, as of the sponsor's last update on 17 Feb 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 21 sites in Spain. 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 is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Evaluate the progression free survival using techniques of image (PET and TC)of Bendamustine in combination with Etoposide, Cytarabine and Melphalan (BeEAM) as conditioning followed by ASCT in patients with aggressive lymphoma. (time frame: 18 months follow-up). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 17 Feb 2016; AzTrials last refreshed its copy on 7 Nov 2026.