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

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Grupo Español de Linfomas y Transplante Autólogo de Médula Ósea
ClinicalTrials.gov Identifier:
NCT01296256
First received: February 13, 2011
Last updated: September 9, 2013
Last verified: September 2013
  Purpose

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.


Condition Intervention Phase
Bendamustine
Conditioning Therapy
Autologous Stem Cell Transplant
Aggressive Non Hodgkin's Lymphoma
Drug: Bendamustine-EAM
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Bendamustine, Cytarabine, Etoposide and Melphalan as Conditioning for Autologous Stem Cell Transplant in Patients With Aggressive Non Hodgkin's Lymphoma.

Resource links provided by NLM:


Further study details as provided by Grupo Español de Linfomas y Transplante Autólogo de Médula Ósea:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • 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 ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 60
Study Start Date: May 2011
Estimated Study Completion Date: November 2015
Estimated Primary Completion Date: November 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Bendamustine-EAM 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

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).

  Eligibility

Ages Eligible for Study:   18 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01296256

Locations
Spain
Complejo Hospitalario Universitario de Santiago
Santiago, A Coruña, Spain, 15706
Hospital Central de Asturias
Oviedo, Asturias, Spain, 33006
Hospital de Jerez
Jerez de la Frontera, Cádiz, Spain, 11407
Hospital Son Llátzer
Palma de Mallorca, Mallorca, Spain, 07198
Hospital Universitario Virgen de Arrixaca
El Palmar, Murcia, Spain, 30120
Clinica Universitaria de Navarra
Pamplona, Navarra, Spain
Hospital Universitario de Canarias
Santa Cruz de Tenerife, Tenerife, Spain
H. de la Santa Creu i Sant Pau
Barcelona, Spain
Hospital Vall d´Hebron
Barcelona, Spain, 08035
Hospital Clinic i Provincial
Barcelona, Spain, 08036
H.U. Gregorio Marañón,
Madrid, Spain
H.U. La Princesa
Madrid, Spain
H.U. La Paz
Madrid, Spain
H.U. 12 de Octubre,
Madrid, Spain
Hospital Ramon y Cajal
Madrid, Spain
H. Clínico Universitario de Salamanca
Salamanca, Spain
H. U. Marqués de Valdecilla.
Santander, Spain
Hospital Clinico de Valencia
Valencia, Spain, 46010
H. La Fe
Valencia, Spain
Hospital Arnau de Vilanova
Valencia, Spain, 46015
Hospital Clínico Lozano Blesa
Zaragoza, Spain, 50009
Sponsors and Collaborators
Grupo Español de Linfomas y Transplante Autólogo de Médula Ósea
Investigators
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 Hospital Gregorio Marañón
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
  More Information

No publications provided

Responsible Party: Grupo Español de Linfomas y Transplante Autólogo de Médula Ósea
ClinicalTrials.gov Identifier: NCT01296256     History of Changes
Other Study ID Numbers: Benda-EAM2010-01, 2010-020926-17
Study First Received: February 13, 2011
Last Updated: September 9, 2013
Health Authority: Spain: Ethics Committee
Spain: Spanish Agency of Medicines

Keywords provided by Grupo Español de Linfomas y Transplante Autólogo de Médula Ósea:
Bendamustine
Conditioning Therapy
Autologous Stem Cell Transplant
Aggressive Non Hodgkin's Lymphoma

Additional relevant MeSH terms:
Aggression
Lymphoma
Lymphoma, Non-Hodgkin
Behavioral Symptoms
Immune System Diseases
Immunoproliferative Disorders
Lymphatic Diseases
Lymphoproliferative Disorders
Neoplasms
Neoplasms by Histologic Type
Bendamustine
Etoposide
Melphalan
Nitrogen Mustard Compounds
Alkylating Agents
Antineoplastic Agents
Antineoplastic Agents, Alkylating
Antineoplastic Agents, Phytogenic
Enzyme Inhibitors
Immunologic Factors
Immunosuppressive Agents
Molecular Mechanisms of Pharmacological Action
Myeloablative Agonists
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses
Topoisomerase II Inhibitors
Topoisomerase Inhibitors

ClinicalTrials.gov processed this record on October 20, 2014