Bendamustine, Cytarabine, Etoposide and Melphalan as Conditioning for Autologous Stem Cell Transplant in Patients With Aggressive Non Hodgkin's Lymphoma.
18 Years
70 Years
Both
Bendamustine, Conditioning Therapy, Autologous Stem Cell Transplant, Aggressive Non Hodgkin's Lymphoma
Trial Information
Bendamustine, Cytarabine, Etoposide and Melphalan as Conditioning for Autologous Stem Cell Transplant in Patients With Aggressive Non Hodgkin's Lymphoma.
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).
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
2. Platelet count
3. Haemoglobin
4. Creatinine serum >o=1,5 x ULN mg/dl
5. Serum bilirubin
6. AST, ALT
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
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.
Type of Study:
Interventional
Study Design:
Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
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.
Outcome Time Frame:
18 months follow-up
Safety Issue:
Yes
Principal Investigator
Mª Dolores Caballero, MD
Investigator Role:
Principal Investigator
Investigator Affiliation:
Hospital Universitario de Salamanca
Authority:
Spain: Ethics Committee
Study ID:
Benda-EAM2010-01
NCT ID:
NCT01296256
Start Date:
May 2011
Completion Date:
November 2015
Related Keywords:
- Bendamustine
- Conditioning Therapy
- Autologous Stem Cell Transplant
- Aggressive Non Hodgkin's Lymphoma
- Bendamustine
- Conditioning Therapy
- Autologous Stem Cell Transplant
- Aggressive Non Hodgkin's Lymphoma
- Aggression
- Lymphoma
- Lymphoma, Non-Hodgkin
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