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

Sponsor

Inje University (Other)

Overall Status

Unknown status

CT.gov ID

NCT01063439

Collaborator

(none)

Enrollment

Locations

Arm

Duration (Months)

8.4

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

Brief 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.

Condition or Disease	Intervention/Treatment	Phase
Non Hodgkin's Lymphoma	Drug: Busulfan, Etoposide, Cytarabine, Melphalan	Phase 2

Detailed 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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

42 participants

Allocation:

Non-Randomized

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

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

Study Start Date :

Jan 1, 2010

Anticipated Primary Completion Date :

Aug 1, 2014

Anticipated Study Completion Date :

Feb 1, 2015

Arms and Interventions

Arm	Intervention/Treatment
Experimental: BuEAM: Experimental BuEAM: Experimental Busulfan 3.2 mg/kg/d for 2 days, etoposide 400 mg/m2/d for 2 days, cytarabine 1 g/m2 for 2 days, and melphalan 140 mg/m2 for 1 day Intervention: Drug: Busulfan, etoposide, cytarabine, and melphalan	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 Other Names: BuEAM conditioning

Arm

Intervention/Treatment

Experimental: BuEAM: Experimental

BuEAM: Experimental Busulfan 3.2 mg/kg/d for 2 days, etoposide 400 mg/m2/d for 2 days, cytarabine 1 g/m2 for 2 days, and melphalan 140 mg/m2 for 1 day Intervention: Drug: Busulfan, etoposide, cytarabine, and melphalan

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

Other Names:

BuEAM conditioning

Outcome Measures

Primary Outcome Measures

progression-free survival [three year]

Secondary Outcome Measures

overall survival [three year]
Response rate according to the International Working Group criteria [after 2 month]
Adverse events [From start of conditioning to discharge]
•Pharmacogenetic study [After 3 years]
Pharmacogenetic study for predictive or prognostic markers using blood samples

Eligibility Criteria

Criteria

Ages Eligible for Study:

N/A to 65 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	Country
1	Inje University Busan Paik Hospital	Busan	Korea, Republic of
2	Asan Medical Center, University of Ulsan	Seoul	Korea, Republic of
3	Seoul National University Hospital	Seoul	Korea, Republic of
4	Yeonsei University Hospital	Seoul	Korea, Republic of
5	Ulsan University Hospital	Ulsan	Korea, Republic of