Chemotherapy and Peripheral Stem Cell Transplant With or Without Monoclonal Antibody Therapy in Treating Patients With Non-Hodgkin's Lymphoma
RATIONALE: Drugs used in chemotherapy work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Peripheral stem cell transplant may be able to replace immune cells that were destroyed by the chemotherapy. Monoclonal antibodies, such as rituximab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. It is not yet known if giving more than one drug (combination chemotherapy) plus peripheral stem cell transplant is more effective with or without monoclonal antibody therapy in treating non-Hodgkin's lymphoma.
PURPOSE: This randomized phase III trial is studying how well chemotherapy plus peripheral stem cell transplant with or without monoclonal antibody therapy works in treating patients with relapsed non-Hodgkin's lymphoma.
|Lymphoma||Biological: filgrastim Biological: rituximab Drug: carmustine Drug: cisplatin Drug: cytarabine Drug: dexamethasone Drug: etoposide Drug: ifosfamide Drug: melphalan Drug: methotrexate Procedure: bone marrow ablation with stem cell support Procedure: peripheral blood stem cell transplantation Radiation: radiation therapy||Phase 3|
|Study Design:||Allocation: Randomized
Primary Purpose: Treatment
|Official Title:||A Randomised Phase III Study On The Effect Of The Chimeric Anti-CD20 Monoclonal Antibody (Mabthera) During Sequential Chemotherapy Followed By Autologous Stem Cell Transplantation In Patients With Relapse B-Cell Non-Hodgkin Lymphoma(HOVON 44 STUDY)|
- Overall survival
- Response rate
- Event-free survival
|Study Start Date:||September 2000|
|Study Completion Date:||October 2007|
- Compare the partial and complete response rates in patients with relapsed, CD20 positive, aggressive B-cell non-Hodgkin's lymphoma treated with dexamethasone, cisplatin, and cytarabine in combination with etoposide, ifosfamide, and methotrexate with or without rituximab followed by carmustine, etoposide, cytarabine, melphalan, and autologous peripheral blood stem cell transplantation (APBSCT).
- Compare the effect of APBSCT with or without rituximab on the overall and event-free survival of these patients.
OUTLINE: This is a randomized, multicenter study. Patients are stratified according to participating center. Patients are randomized to one of two treatment arms.
- Arm I: Patients receive DHAP induction chemotherapy comprising dexamethasone orally or IV on days 1-4, cisplatin IV continuously over 24 hours on day 1, and cytarabine IV over 3 hours every 12 hours on day 2. Beginning 3-4 weeks after DHAP, patients receive VIM induction chemotherapy comprising etoposide IV over 2 hours on days 1, 3, and 5; ifosfamide IV over 1 hour on days 1-5; and methotrexate IV on days 1 and 5. Beginning 3-4 weeks after VIM, patients with partial or complete response after DHAP and VIM receive a second course of DHAP (patients with progressive or unresponsive disease after DHAP but responsive disease after VIM receive a second course of VIM) followed by filgrastim (G-CSF) subcutaneously beginning on day 10 and continuing until a target number of cells are collected.
- Arm II: Patients receive induction chemotherapy and G-CSF as in arm I. At 1 day after the last dose of each chemotherapy course, patients also receive rituximab IV once for a maximum of 3 courses.
At 4-5 weeks after the completion of the last induction chemotherapy course, responsive patients in both arms receive BEAM conditioning chemotherapy comprising carmustine IV over 60 minutes on day -6, etoposide IV over 60 minutes and cytarabine IV over 30 minutes on days -5 to -2, and melphalan IV over 15 minutes on day -1. Patients undergo autologous peripheral blood stem cell transplantation on day 0. After transplantation, patients in partial remission may undergo radiotherapy to nodal sites with residual tumor mass.
Patients are followed every 6 months for 3 years and then annually thereafter.
PROJECTED ACCRUAL: A total of 296-340 patients (148-170 per treatment arm) will be accrued for this study within 4-5 years.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00012051
|Leuven, Belgium, B-3000|
|HagaZiekenhuis - Locatie Leyenburg|
|'s-Gravenhage, Netherlands, 2545 CH|
|Jeroen Bosch Ziekenhuis|
|'s-Hertogenbosch, Netherlands, 5211 NL|
|Meander Medisch Centrum|
|Amersfoort, Netherlands, 3816 CP|
|Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital|
|Amsterdam, Netherlands, 1066 BE|
|Vrije Universiteit Medisch Centrum|
|Amsterdam, Netherlands, 1081HV|
|Academisch Medisch Centrum at University of Amsterdam|
|Amsterdam, Netherlands, 1105 AZ|
|Medisch Spectrum Twente|
|Enschede, Netherlands, 7500 KA|
|University Medical Center Groningen|
|Groningen, Netherlands, 9713 EZ|
|Medisch Centrum Leeuwarden - Zuid|
|Leeuwarden, Netherlands, 8934 AD|
|Leiden University Medical Center|
|Leiden, Netherlands, 2300 CA|
|Academisch Ziekenhuis Maastricht|
|Maastricht, Netherlands, 6202 AZ|
|Sint Antonius Ziekenhuis|
|Nieuwegein, Netherlands, 3435 CM|
|Universitair Medisch Centrum St. Radboud - Nijmegen|
|Nijmegen, Netherlands, NL-6500 HB|
|Daniel Den Hoed Cancer Center at Erasmus Medical Center|
|Rotterdam, Netherlands, 3008 AE|
|University Medical Center Utrecht|
|Utrecht, Netherlands, 3584 CX|
|Isala Klinieken - locatie Sophia|
|Zwolle, Netherlands, 8000 GK|
|Study Chair:||Edo Vellenga, MD||University Medical Center Groningen|