Clinical trial NCT00336843: Zevalin Plus BuCyE High-dose Therapy in B-cell Non-Hodgkin's Lymphoma
Official title: Combining 90Y-ibritumomab Tiuxetan With High-dose Chemotherapy of BuCyE and Autologous Stem Cell Transplantation in Patients With B-cell Non-Hodgkin's Lymphoma - an Open-labeled Phase II Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Non-Hodgkin's Lymphoma
Keywords: Zevalin
B-cell non-Hodgkin's lymphoma
autologous stem cell transplantation
BuCyE regimen
Lead sponsor: Asan Medical Center
Sponsor class: OTHER
Collaborators: name: Schering-Plough
First posted: 2006-06-14
Enrollment: 19
Sex: ALL
Maximum age (years): 64
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: In order to improve the clinical result of high-dose chemotherapy and autologous stem cell transplantation for B-cell non-Hodgkin's lymphoma, Zevalin will be added to the conditioning regimen. Investigators expect this radioimmunotherapy of Zevalin plus busulfan, cyclophosphamide and etoposide regimen will improve survival of relapsed or poor-risk B-cell non-Hodgkin's lymphoma.

Detailed description: Title: Combining 90Y-Ibritumomab tiuxetan (Zevalin) with high-dose chemotherapy of BuCyE and autologous stem cell transplantation in patients with relapsed, refractory, or high-risk B-cell non-Hodgkin's lymphoma - an open-labeled phase II study.

Study design: Prospective, multicenter, open-labeled, phase II trial.

Study objectives:

* Primary: event-free survival time following autologous stem cell transplantation with 90Y-Ibritumomab tiuxetan and BuCyE high-dose chemotherapy in patients with relapsed, refractory, or high-risk B-cell non-Hodgkin's lymphoma
* Secondary: overall survival response rate toxicity of the treatment combination

Treatment:

Z-BuCyE Regimen

* Day 21: rituximab, 250 mg/m2, I.V.
* Day 14: rituximab, 250 mg/m2, I.V. 90Y-Ibritumomab tiuxetan, 0.4 mCi/kg, I.V.
* Day 7, 6, 5: busulfan 3.2 mg/kg I.V.
* Day 5, 4: etoposide 200 mg/m2 I.V. every 12 hours
* Day 3, 2: Cytoxan 50 mg/kg I.V.
* Day 0: autologous stem cell infusion

Eligibility criteria: Inclusion Criteria:

* Histologically confirmed B-cell NHL in chemotherapy-sensitive relapse, in partial response to 1st line chemotherapy, or in complete response after 1st line chemotherapy with high IPI score at diagnosis
* Age \< 65 years old
* WHO performance status (PS) of 0-2
* ANC \> 1,500/mm3, platelet \> 100,000/mm3
* Cr \< 2.0 mg% or Ccr \> 50 mL/min
* Transaminase \< 3X upper normal value
* Bilirubin \< 2 mg/dL
* Life expectancy of at least 3 months
* Written informed consent
* Optimal harvest of autologous stem cells (CD34+ cells \> 5 million/kg plus 2 million/kg for back-up)

Exclusion Criteria:

* Prior hematopoietic stem cell transplantation
* Prior RIT
* Prior external radiation to \> 25% of active bone marrow
* CNS involvement of non-Hodgkin's lymphoma
* Serious comorbid diseases
* HIV or HTLV-1 associated malignancy
* History of other malignant disease in the previous 5 years, except squamous cell or basal cell carcinoma of skin or stage I uterine cervical carcinoma or cervical carcinoma in situ
* Known hypersensitivity to murine antibodies/proteins
* Pregnant or breast feeding female patients, adults without effective contraception up to 12 months after RIT
* Persistent toxic side effects from prior therapy
* Prior biologic or immunotherapy less than 4 weeks prior to entry on this study
* Investigational drugs less than 4 weeks prior to entry on this study

Primary outcomes:
measure: Event-free survival
timeFrame: the time from stem cell infusion to failure or death from any cause
Secondary outcomes:
measure: Overall survival
timeFrame: from stem cell infusion to death of any cause or last follow-up
measure: Toxicity of the treatment combination
timeFrame: any toxicity due to study treatment during study period
Other outcomes:
Locations:
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center, Departement of Internal Medicine, Division of Oncology
Study officials:
affiliation: Asan Medical Center
name: Cheolwon Suh, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Kang BW, Kim WS, Kim C, Jang G, Lee SS, Choi YH, Lee DH, Kim SW, Kim S, Ryu JS, Huh J, Lee JS, Suh C. Yttrium-90-ibritumomab tiuxetan in combination with intravenous busulfan, cyclophosphamide, and etoposide followed by autologous stem cell transplantation in patients with relapsed or refractory B-cell non-Hodgkin's lymphoma. Invest New Drugs. 2010 Aug;28(4):516-22. doi: 10.1007/s10637-009-9283-z. Epub 2009 Jun 23.