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Bendamustine, Cytarabine, Etoposide and Melphalan (BeEAM) as Conditioning for Autologous Stem Cell Transplant (ASCT) in Aggressive Non Hodgkin's Lymphoma (NHL). (BeEAM2010-01)

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ClinicalTrials.gov Identifier: NCT01296256
Recruitment Status : Completed
First Posted : February 15, 2011
Last Update Posted : February 17, 2016
Sponsor:
Information provided by (Responsible Party):
Grupo Español de Linfomas y Transplante Autólogo de Médula Ósea

Tracking Information
First Submitted Date  ICMJE February 13, 2011
First Posted Date  ICMJE February 15, 2011
Last Update Posted Date February 17, 2016
Study Start Date  ICMJE May 2011
Actual Primary Completion Date November 2015   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: February 14, 2011)
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 ]
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: February 14, 2011)
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 ]
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Bendamustine, Cytarabine, Etoposide and Melphalan (BeEAM) as Conditioning for Autologous Stem Cell Transplant (ASCT) in Aggressive Non Hodgkin's Lymphoma (NHL).
Official Title  ICMJE Bendamustine, Cytarabine, Etoposide and Melphalan as Conditioning for Autologous Stem Cell Transplant in Patients With Aggressive Non Hodgkin's Lymphoma.
Brief 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.
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 Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Bendamustine
  • Conditioning Therapy
  • Autologous Stem Cell Transplant
  • Aggressive Non Hodgkin's Lymphoma
Intervention  ICMJE Drug: Bendamustine-EAM
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 Arms  ICMJE Experimental: Bendamustine-EAM
Intervention: Drug: Bendamustine-EAM
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: February 14, 2011)
60
Original Estimated Enrollment  ICMJE Same as current
Actual Study Completion Date  ICMJE November 2015
Actual Primary Completion Date November 2015   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. Patients being able to meet all requirements of the clinical trial, according to the investigator's criteria,
  2. Patient giving voluntarily written informed consent before performing any essay test that is not part of routine care of patients.
  3. Age >o=18 years and >0=70 years
  4. Candidate for chemotherapy (QT) at high doses and ASCT

    1. Histologically confirmed aNHL:
    2. 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.
    3. 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.
    4. Transformed B cell lymphoma in first CR
    5. Patients with PTCL (other than anaplastic ALK +) in first CR
  5. Performance status (ECOG) <0=2.
  6. Adequate renal, hepatic, and bone marrow function (assessed < 14 days before initiation of the study treatment):

    1. Neutrophil count <o=1.5 x 109/L
    2. Platelet count <o=100 x 109/L
    3. Haemoglobin <o=8.0 g/dL
    4. Creatinine serum >o=1,5 x ULN mg/dl
    5. Serum bilirubin <o=1.5 x ULN and alkaline phosphatase <o=2.5 x ULN
    6. AST, ALT <o=2.5 x ULN (<o=5 x ULN in case of liver metastasis).
  7. Adequate pulmonary function: forced expiratory volume at 1 second > 65% of predicted or a diffusing capacity of the lung for CO >o=50%.
  8. Cardiac ejection fraction or greater than 50% by echocardiogram or FEVI.
  9. 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:

  1. has not undergone hysterectomy or bilateral oophorectomy and
  2. 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).

Exclusion Criteria:

  1. Impossibility of collecting, via apheresis, a number of CD34+ cells >o=2 x 106/kg
  2. 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.

  3. Known involvement of the central nervous system (CNS) by lymphoma
  4. 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.
  5. Other serious or uncontrolled medical condition, such as uncontrolled diabetes, uncontrolled active infection, significant cerebrovascular disease or poorly controlled psychiatric disease.
  6. Known or suspected hypersensitivity to any of the agents or excipients of the regime under evaluation.
  7. Presence of any limitations that compromise the patient's ability to comply with the study treatment.
  8. 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.
  9. 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.
  10. Major surgery procedure within 30 days prior to entering this study.
  11. Pregnant or nursing females.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 70 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Spain
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01296256
Other Study ID Numbers  ICMJE Benda-EAM2010-01
2010-020926-17 ( EudraCT Number )
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Grupo Español de Linfomas y Transplante Autólogo de Médula Ósea
Study Sponsor  ICMJE Grupo Español de Linfomas y Transplante Autólogo de Médula Ósea
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Mª Dolores Caballero, MD Hospital Universitario de Salamanca
Principal Investigator: Alejandro Martín, MD Hospital Universitario de Salamanca
Principal Investigator: Javier Briones, MD Hospital Santa Creu i Sant Pau
Principal Investigator: Juan Manuel Sancho, MD Germans Trias i Pujol Hospital
Principal Investigator: Cristina Barrenetxea, MD Hospital Vall d'Hebrón
Principal Investigator: Javier López, MD Hospital Universitario Ramon y Cajal
Principal Investigator: Mª José Rodríguez, MD Hospital Universitario de Canarias
Principal Investigator: Jorge Gayoso, MD Gregorio Marañón Hospital
Principal Investigator: Miguel Ángel Canales, MD Hospital Universitario La Paz
Principal Investigator: Carlos Grande, MD Hospital Universitario 12 de Octubre
Principal Investigator: Isidro Jarque, MD Hospital La Fe
Principal Investigator: José Rifón, MD Clínica Universitaria Navarra
Principal Investigator: Andres Sánchez, MD Hospital Virgen de la Arrixaca
Principal Investigator: Cristina Castilla, MD Hospital Morales Meseguer
Principal Investigator: José Luis Bello, MD Complejo Hospitalario Universitario de Santiago de Compostela
Principal Investigator: Armando López, MD Hospial Clínic de Barcelona
Principal Investigator: Eulogio Conde, MD Hospital Marqués de Valdecilla
Principal Investigator: Reyes Arranz, MD Hospital La Princesa
Principal Investigator: Encarnación Monzó, MD Hospital Arnau de Vilanova de Valencia
Principal Investigator: Rosario Varela, MD Complejo Hospitalario Universitario de A Coruña
Principal Investigator: Mª José Ramírez, MD Hospital Jerez de la Frontera
Principal Investigator: Fátima de la Cruz, MD Hospital Virgen del Rocío
Principal Investigator: Ana Pilar González, MD Hospital Central de Asturias
Principal Investigator: Luis Palomera, MD Hospital Clínico de Zaragoza "Lozano Blesa"
Principal Investigator: Raquel del Campo, MD Hospital Son Llátzer
Principal Investigator: Mª José Terol, MD Hospital Clínico de Valencia
PRS Account Grupo Español de Linfomas y Transplante Autólogo de Médula Ósea
Verification Date February 2016

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP