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

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

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).

Study Overview

• Status: Completed
• Conditions: Non-hodgkin Lymphoma
• Intervention / Treatment: Drug: Busulfan; Drug: Cyclophosphamide; Drug: Etoposide; Drug: Melphalan

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 75
• Phase: Phase 2

Contacts and Locations

Study Locations

• Korea, Republic of
  • Seoul, Korea, Republic of, 04401
    • Jong-Ho Won

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Histologically confirmed aggressive NHL
2. Mantle cell lymphoma
3. salvage chemotherapy sensitive relapse/refractory NHL or high risk NHL with remission in induction chemotherapy
4. Performance status: Eastern Cooperative Oncology Group (ECOG) 0-2.
5. Age; 18-65
6. Adequate renal function: serum creatinine ≤ 1.5mg/dL
7. Adequate liver functions: Transaminase (AST/ALT) < 3 X upper normal value & Bilirubin < 2 X upper normal value

Exclusion Criteria:

1. low grade NHL
2. Any other malignancies within the past 5 years except curatively treated non-melanoma skin cancer or in situ carcinoma of cervix uteri

3. 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)
4. Pregnant or lactating women, women of childbearing potential not employing adequate contraception
5. HIV (+)
6. 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 -

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Soonchunhyang University Hospital
• Investigators: Principal Investigator: Jong-Ho Won, Professor, Soonchunhyang University Hospital

Study record dates

Study Major Dates

• Study Start (Actual): June 1, 2012
• Primary Completion (Actual): May 30, 2017
• Study Completion (Actual): November 30, 2018

Study Registration Dates

• First Submitted: January 3, 2019
• First Submitted That Met QC Criteria: January 3, 2019
• First Posted (Actual): January 4, 2019

Study Record Updates

• Last Update Posted (Actual): January 7, 2019
• Last Update Submitted That Met QC Criteria: January 3, 2019
• Last Verified: January 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Lymphoma; Lymphoma, Non-Hodgkin; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antirheumatic Agents; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Antineoplastic Agents, Alkylating; Alkylating Agents; Myeloablative Agonists; Antineoplastic Agents, Phytogenic; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Cyclophosphamide; Etoposide; Melphalan; Busulfan
• Other Study ID Numbers: CISL 12-05

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No