BuCE Versus BuME as Conditioning Therapy in Non-Hodgkin's Lymphoma

Study Overview
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Brief Summary
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The investigators developed a protocol comparing busulfan/cyclophosphamide/etoposide (BuCE) and busulfan/melphalan/etoposide (BuME) regimen as a conditioning for high-dose therapy (HDT) in the patients with high risk or relapsed Non-Hodgkin's Lymphoma (NHL).

Detailed Description
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Intravenous busulfan containing regimens as conditioning regimen have been used for both allogeneic and autologous stem cell transplantation in patients with hematologic and non-hematologic malignancies. The investigators have previously studied that conditioning regimen of i.v. busulfan/melphalan/etoposide (BuME) was well tolerated and effective in patients with relapsed or high risk NHL. And busulfan/cyclophosphamide/etoposide (BuCE) conditioning regimen has been extensively utilized in ASCT for NHL. Therefore, based on the encouraging results, the investigators will conduct a randomized phase II multicenter trial of BuCE versus BuME as conditioning therapy for ASCT in patients with NHL.

Official Title
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Randomized Phase II Multi-center Trial of Busulfan, Etoposide, and Cyclophosphamide Versus Busulfan, Etoposide, and Melphalan as Conditioning Therapy for Autologous Stem-cell Transplantation(ASCT) in Patients With Non-Hodgkin's Lymphoma

Conditions
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Non-hodgkin Lymphoma

Intervention / Treatment
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* Drug: Busulfan
* Drug: Cyclophosphamide
* Drug: Etoposide
* Drug: Melphalan


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically confirmed aggressive NHL Mantle cell lymphoma salvage chemotherapy sensitive relapse/refractory NHL or high risk NHL with remission in induction chemotherapy Performance status: Eastern Cooperative Oncology Group (ECOG) 0-2. Age; 18-65 Adequate renal function: serum creatinine ≤ 1.5mg/dL Adequate liver functions: Transaminase (AST/ALT) < 3 X upper normal value & Bilirubin < 2 X upper normal value Exclusion Criteria: low grade NHL Any other malignancies within the past 5 years except curatively treated non-melanoma skin cancer or in situ carcinoma of cervix uteri Other serious illness or medical conditions Unstable cardiac disease despite treatment, myocardial infarction within 6 months prior to study entry History of significant neurological or psychiatric disorders Active uncontrolled infection (viral, bacterial or fungal infection) Pregnant or lactating women, women of childbearing potential not employing adequate contraception HIV (+) Patients who have hepatitis B virus (HBV) (+) are eligible. However, primary prophylaxis using antiviral agents (i.e. lamivudine) is recommended for HBV carrier to prevent HBV reactivation during whole treatment period -

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 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
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Parallel assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: busulfan cyclophosphamide etoposide<br>busulfan 3.2 mg/kg/day i.v. on days -8,-7, and -6, cyclophosphamide 50mg/kg/day i.v. on days -3 and -2 etoposide 400mg/m2 day i.v. on days -5 and -4 | Drug: Busulfan<br>* busulfan 3.2 mg/kg/day i.v. on days -8,-7, and -6<br>* Other names: Busulfex;Drug: Cyclophosphamide<br>* cyclophosphamide 50mg/kg/day i.v. on days -3 and -2<br>Drug: Etoposide<br>* etoposide 400mg/m2 day i.v. on days -5 and -4<br>|
| Active Comparator: busulfan melphalan etoposide<br>busulfan 3.2 mg/kg/day i.v. on days -8,-7, and -6 melphalan 50mg/m2/day i.v. on days -3 and -2 etoposide 400mg/m2 day i.v. on days -5 and -4 | Drug: Busulfan<br>* busulfan 3.2 mg/kg/day i.v. on days -8,-7, and -6<br>* Other names: Busulfex;Drug: Etoposide<br>* etoposide 400mg/m2 day i.v. on days -5 and -4<br>Drug: Melphalan<br>* melphalan 50mg/m2/day i.v. on days -3 and -2<br>* Other names: Alkeran;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of progression free survival | calculate from the date of ASCT until the time of disease progression, relapse, or death calculate from the date of ASCT until the time of disease progression, relapse, or death calculate from the date of ASCT until the time of disease progression, relapse, or death Calculate from the date of ASCT (autologous stem cell transplantation) until the time of disease progression, relapse, or death | 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of overall survival | calculate from the date of ASCT until the time of death from any causes | 2 years | 
| Rate of regimen related toxicity | calculate toxicities frequency | 6 months |