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

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

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.

Study Overview

• Status: Unknown
• Conditions: Non Hodgkin's Lymphoma
• Intervention / Treatment: Drug: Busulfan, Etoposide, Cytarabine, Melphalan

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 Type: Interventional
• Enrollment (Anticipated): 42
• Phase: Phase 2

Contacts and Locations

Study Locations

• Korea, Republic of
  • Busan, Korea, Republic of
    • Recruiting
    • Inje University Busan Paik Hospital
    • Contact: Won Sik Lee, Dr. PhD.; Phone Number: +82-51-890-6407; Email: wonsik112@gmail.com
    • Principal Investigator: Won Sik Lee, M.D. PhD.
  • Seoul, Korea, Republic of
    • Recruiting
    • Seoul National University Hospital
    • Principal Investigator: Sung Soo Yoon, M.D. Ph.D.
  • Seoul, Korea, Republic of
    • Recruiting
    • Asan Medical Center, University of Ulsan
    • Principal Investigator: Je Hwan Lee, M.D. Ph.D.
  • Seoul, Korea, Republic of
    • Recruiting
    • Yeonsei University Hospital
    • Principal Investigator: Jin Seok Kim, M.D. Ph.D.
  • Ulsan, Korea, Republic of
    • Recruiting
    • Ulsan University Hospital
    • Principal Investigator: Hawk Kim, M.D. Ph. D.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 65 years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
progression-free survival	three year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	Pharmacogenetic study for predictive or prognostic markers using blood samples	After 3 years

Collaborators and Investigators

• Sponsor: Inje University
• Investigators: Principal Investigator: Won Sik Lee, Dr. PhD., Inje University

Study record dates

Study Major Dates

• Study Start: January 1, 2010
• Primary Completion (Anticipated): August 1, 2014
• Study Completion (Anticipated): February 1, 2015

Study Registration Dates

• First Submitted: February 4, 2010
• First Submitted That Met QC Criteria: February 4, 2010
• First Posted (Estimate): February 5, 2010

Study Record Updates

• Last Update Posted (Estimate): December 2, 2010
• Last Update Submitted That Met QC Criteria: December 1, 2010
• Last Verified: August 1, 2010

More Information

Terms related to this study

• Keywords: DLBCL; NHL
• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Lymphoma, Non-Hodgkin; Lymphoma, B-Cell; Lymphoma; Lymphoma, Large B-Cell, Diffuse; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Antineoplastic Agents, Alkylating; Alkylating Agents; Myeloablative Agonists; Antineoplastic Agents, Phytogenic; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Etoposide; Melphalan; Cytarabine; Busulfan
• Other Study ID Numbers: BuEAM-DLBCL

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No