BuEAM Conditioning for Autologous Stem Cell Transplantation (ASCT) to Treat Diffuse Large B Cell Lymphoma (DLCBL)

Non Hodgkin's Lymphoma Clinical Trial

Official title:

Busulfan, Etoposide, Cytarabine and Melphalan (BuEAM) as a Conditioning for Autologous Stem Cell Transplantation in Patients With Diffuse Large B Cell Lymphoma (DLCBL) Previously Treated With Rituximab Based Regimen

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT01063439
• Other study ID #: BuEAM-DLBCL
• Status: Recruiting
• Phase: Phase 2
• First received: February 4, 2010
• Last updated: December 1, 2010
• Start date: January 2010
• Est. completion date: February 2015

Study information

• Verified date: August 2010
• Source: Inje University
• Contact: Won Sik Lee, Dr. PhD.
• Phone: 82-51-890-6407
• Email: wonsik112[@]gmail.com
• Is FDA regulated: No
• Health authority: Korea: Institutional Review Board
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to evaluate the efficacy and toxicity of busulfan, etoposide, cytarabine and melphalan (BuEAM) including intravenous busulfan instead of BCNU of standard BEAM as a conditioning for autologous stem cell transplantation in patients with NHL.

Description:

Among the high-dose conditioning regimens commonly used in patients with NHL are BEAM (BCNU, etoposide, cytarabine, and melphalan), BEAC (BCNU, etoposide, cytarabine, and cyclophosphamide), CBV (cyclophosphamide, carmustine, etoposide), and combination regimen with total body irradiation. Three-year progression free survival of patients with NHL received above high-dose chemotherapy followed by autologous stem cell rescue was reported as 40-50%, which is still unsatisfactory.

Busulfan (Bu)-based preparative regimens, which are commonly used with allogeneic SCT have also been studied with ASCT for lymphomas.

The development of intravenous busulfan achieved 100% bioavailability bypassing the oral route and increased safety and reliability of generating therapeutic busulfan levels, maximizing efficacy.

Recently, one prospective study showed that a combination conditioning regimen of i.v. busulfan, cyclophosphamide, etoposide was found to be well tolerated and seemed to be effective in patients with aggressive NHL.

Another prospective study for multiple myeloma patients showed that i.v. busulfan and melphalan conditioning regimen made no grade 3-4 non-hematological complication.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 42
• Est. completion date: February 2015
• Est. primary completion date: August 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: N/A to 65 Years

Eligibility

Inclusion Criteria:

• Patients with a high-intermediate/high risk international prognostic index at a diagnosis or with salvage chemotherapy-sensitive relapse/refractory non Hodgkin's lymphoma

• Patients with histologically confirmed diffuse large B cell lymphoma at diagnosis

• Patients treated with rituximab based regimen previously

• Patients who have not received therapy with high-dose chemotherapy and stem cell transplantation

• Life expectation of at least 3 months

• ECOG performance status = 2 (See Appendix II)

• Adequate hepatic function (serum bilirubin less than 2.0 mg/dL, AST and ALT less than three times the upper normal limit)

• Adequate renal function (serum creatinine less than 2.0 mg/dL).

• Adequate cardiac function (ejection fraction = 45% on MUGA scan or echocardiogram).

• Adequate bone marrow function (ANC = 1,000/mm3 and platelet count = 75,000/mm3).

• All patients are fully informed about the nature and purpose of this study and informed consent should be given before the start of treatment. All patients should fully understand the right of trial abandon without any disadvantage

Exclusion Criteria:

• Patients with central nervous system involvement of lymphoma

• Patients positive for human immunodeficiency virus

• Pregnant or breast feeding woman

• Young woman without pregnancy test prior to treatment or pregnancy test reveals positive.

• Young woman without a reliable and proper contraceptive method

• Man being not willing to contraception

• Concurrent history of neoplasm other than NHL with life expectancy less than 3 months (except for curatively treated non-melanoma skin cancer or in-situ uterine cervix cancer).

• History of clinically significant cardiac dysfunction (e.g. congestive heart failure, symptomatic coronary artery disease, medically uncontrolled arrhythmia) or myocardial infarction within 12 months

• A psychiatric disorder or mental deficiency severe as to make compliance with the treatment unlike, and making informed consent impossible.

• Significant infection or uncontrolled bleeding

• Enrollment of other clinical trials within 4 weeks prior to treatment

• Any preexisting medical condition of sufficient severity to prevent full compliance with the study

• Patient being not willing to or unable to obey study protocol

Study Design

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

Related Conditions & MeSH terms

• Lymphoma
• Lymphoma, B-Cell
• Lymphoma, Large B-Cell, Diffuse
• Lymphoma, Non-Hodgkin
• Non Hodgkin's Lymphoma

Intervention

Drug:
• Busulfan, Etoposide, Cytarabine, Melphalan
Busulfan 3.2 mg/kg/d for 2 days Etoposide 400 mg/m2/d for 2days Cytarabine 1 g/m2 for 2 days Melphalan 140 mg/m2 for 1 day

Locations

Country	Name	City	State
Korea, Republic of	Inje University Busan Paik Hospital	Busan
Korea, Republic of	Asan Medical Center, University of Ulsan	Seoul
Korea, Republic of	Seoul National University Hospital	Seoul
Korea, Republic of	Yeonsei University Hospital	Seoul
Korea, Republic of	Ulsan University Hospital	Ulsan

Sponsors (1)

Lead Sponsor	Collaborator
Inje University

Country where clinical trial is conducted

Korea, Republic of, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	progression-free survival		three year	No
Secondary	overall survival		three year	No
Secondary	Response rate according to the International Working Group criteria		after 2 month	No
Secondary	Adverse events		From start of conditioning to discharge	Yes
Secondary	•Pharmacogenetic study	Pharmacogenetic study for predictive or prognostic markers using blood samples	After 3 years	Yes