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

Autologous Stem Cell Transplant Clinical Trial

— BeEAM2010-01  

Official title:

Bendamustine, Cytarabine, Etoposide and Melphalan as Conditioning for Autologous Stem Cell Transplant in Patients With Aggressive Non Hodgkin's Lymphoma.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01296256
• Other study ID #: Benda-EAM2010-01
• Secondary ID: 2010-020926-17
• Status: Completed
• Phase: Phase 2
• First received: February 13, 2011
• Last updated: February 15, 2016
• Start date: May 2011
• Est. completion date: November 2015

Study information

• Verified date: February 2016
• Source: Grupo Español de Linfomas y Transplante Autólogo de Médula Ósea
• Contact: n/a
• Is FDA regulated: No
• Health authority: Spain: Ethics CommitteeSpain: Spanish Agency of Medicines
• Study type: Interventional

Clinical 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.

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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 60
• Est. completion date: November 2015
• Est. primary completion date: November 2015
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 70 Years

Eligibility

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.

Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Aggression
• Aggressive Non Hodgkin's Lymphoma
• Autologous Stem Cell Transplant
• Bendamustine
• Conditioning Therapy
• Lymphoma
• Lymphoma, Non-Hodgkin

Intervention

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

Locations

Country	Name	City	State
Spain	H. de la Santa Creu i Sant Pau	Barcelona
Spain	Hospital Clinic i Provincial	Barcelona
Spain	Hospital Vall d´Hebron	Barcelona
Spain	Hospital Universitario Virgen de Arrixaca	El Palmar	Murcia
Spain	Hospital de Jerez	Jerez de la Frontera	Cádiz
Spain	H.U. 12 de Octubre,	Madrid
Spain	H.U. Gregorio Marañón,	Madrid
Spain	H.U. La Paz	Madrid
Spain	H.U. La Princesa	Madrid
Spain	Hospital Ramon y Cajal	Madrid
Spain	Hospital Central de Asturias	Oviedo	Asturias
Spain	Hospital Son Llátzer	Palma de Mallorca	Mallorca
Spain	Clinica Universitaria de Navarra	Pamplona	Navarra
Spain	H. Clínico Universitario de Salamanca	Salamanca
Spain	Hospital Universitario de Canarias	Santa Cruz de Tenerife	Tenerife
Spain	H. U. Marqués de Valdecilla.	Santander
Spain	Complejo Hospitalario Universitario de Santiago	Santiago	A Coruña
Spain	H. La Fe	Valencia
Spain	Hospital Arnau de Vilanova	Valencia
Spain	Hospital Clinico de Valencia	Valencia
Spain	Hospital Clínico Lozano Blesa	Zaragoza

Sponsors (1)

Lead Sponsor	Collaborator
Grupo Español de Linfomas y Transplante Autólogo de Médula Ósea

Country where clinical trial is conducted

Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.		18 months follow-up	Yes
Secondary	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		18 months follow-up	Yes