BeEAC Conditioning Regimen in Malignant Lymphoma Subjects With Indications to Autologous Hematopoietic Stem-cell Transplantation

Study Overview
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Brief Summary
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Nowadays there is no randomized trials for comparison the effectiveness and tolerability of different conditioning regimens. Bendamustine is a unique chemotherapeutic agent that combines alkylating action of nitrogen mustard and the activity of purine antimetabolite. Bendamustine has shown its effectiveness for the treatment of patients with chronic lymphoproliferative diseases such as chronic lymphocytic leukemia and several indolent lymphomas. The literature also presents evidence of the effectiveness bendamustine in patients with Hodgkin's lymphoma who received multiple lines of prior chemotherapy, including high dose chemotherapy and transplantation of peripheral hematopoietic stem cells. There are also data of using bendamustine as a part of conditioning regimen. In this context, it was planned a study for evaluation the safety and effectiveness of the BeEAC (bendamustine, etoposide, cytarabine, cyclophosphamide) conditioning regimen prior to autologous transplantation of peripheral hematopoietic stem cells for the treatment of relapsed/refractory malignant lymphomas.

Official Title
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A Phase II, Multicenter, Prospective, Non-randomised, Open-label, Clinical Trial to Evaluate Effectiveness and Safety of BeEAC Conditioning Regimen in Malignant Lymphoma Subjects With Indications to Autologous Hematopoietic Stem-cell Transplantation

Conditions
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Relapsed/Refractory Malignant Lymphomas

Intervention / Treatment
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* Drug: Bendamustine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Be willing and able to provide written informed consent for the trial Be ≥ 18 years of age on day of signing informed consent Eastern Cooperative Oncology Group (ECOG) < 2. Relapsed/refractory malignant lymphoma patients with indications to autologous hematopoietic stem-cell transplantation Exclusion Criteria: Participation in another clinical trials Clinically relevant heart disease: Myocardial infarction during previous 6 months Unstable angina during previous 3 months Congestive heart failure (III-IV NYHA) Clinically relevant ventricular arrhythmias corrected QT interval (QTc) > 460 мс on ECG (calculated using Frederics formula) Left ventricular ejection fraction ≤ 45% on Echocardiogram Atrial Hypotension (systolic pressure < 86 mmHg) or bradycardia (< 50 per minute, exclusion - drug-induced bradycardia) Uncontrolled arterial hypertension (systolic pressure > 170 mmHg or diastolic pressure > 105 mmHg) Severe renal dysfunction (serum creatinine > 250 µmol/l) Severe hepatic dysfunction (total bilirubin > 40 µmol/l) Known history of Human Immunodeficiency Virus or active Hepatitis B and C Psychiatric or substance abuse disorders that would interfere with the cooperation with the requirements of the trial Hypersensitivity to investigational drugs Pregnant or breastfeeding females or males and females with childbearing potential must be willing to use an adequate method of birth control (intrauterine device, vasectomy of female subjects' male partner, contraceptive rod implanted into the skin, combination method - (requires use of two of the following) diaphragm with spermicide, cervical cap spermicide, contraceptive sponge, condom, hormonal contraceptive)

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Relapsed/refractory malignant lymphomas<br>Malignant Lymphoma Subjects With Indications to Autologous Hematopoietic Stem-cell Transplantation using BeEAC (Bendamustine, Cytarabine, Etoposide, Cyclophosphamide) conditioning regimen | Drug: Bendamustine<br>* BeEAC conditioning regimen: bendamustine 200 mg/м2 D-6 - D-5; cytarabine 400 mg/м2 D-4 - D-1; etoposide 400 mg/м2 D-4 - D-1; cyclophosphamide 140 mg/м2 totally, divided in 4 days (D-4 - D-1)<br>* Other names: Cyclophosphamide;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of Treatment-Emergent Adverse Events | The primary safety analysis will be based on subjects who experienced toxicities as defined by CTCAE criteria. Safety will be assessed by quantifying the toxicities and grades experienced by subjects who have received BeEAC including serious adverse events (SAEs). Adverse experiences will be graded and recorded throughout the study and during the follow-up period according to NCI CTCAE 4.03. Toxicities will be characterized in terms regarding seriousness, causality, toxicity grading and action taking with regard to trial treatment (Incidence of Treatment-Emergent Adverse Events). | From admission till discharge from the hospital (approximately 30 days) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival |  | 2 years | 
| Progression-Free Survival |  | 2 years | 
| Retrospective Comparison of Overall Survival between Carmustine, Etoposide, Cytarabine, Melphalan (BEAM), Cyclophosphamide, Carmustine, Etoposide(CBV) and BeEAC conditioning regimens | The analysis will be based on comparison of overall survival between different conditioning regimens | 2 years | 
| Retrospective Comparison of Progression-Free Survival between Carmustine, Etoposide, Cytarabine, Melphalan (BEAM), Cyclophosphamide, Carmustine, Etoposide(CBV) and BeEAC conditioning regimens | The analysis will be based on comparison of Progression-Free survival between different conditioning regimens | 2 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Hodgkin Lymphoma, Non-Hodgkin lymphoma, autologous hematopoietic stem-cell transplantation, conditioning regimen