Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outcomes
Outline
Published Results
Trial Contact Information
Registry Information

Alternate Title

Chemotherapy and Peripheral Stem Cell Transplant With or Without Monoclonal Antibody Therapy in Treating Patients With Non-Hodgkin's Lymphoma

Basic Trial Information

Phase	Type	Status	Age	Sponsor	Protocol IDs
Phase III	Treatment	Active	18 to 65	Other	CKTO-2000-06 HOVON-44, HOVON-44/CKVO-2000-06, EU-20042, ISRCTN95614846, NCT00012051

Objectives

1. 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).
2. Compare the effect of APBSCT with or without rituximab on the overall and event-free survival of these patients.

Entry Criteria

Disease Characteristics:

• Histologically confirmed relapsed B-cell non-Hodgkin's lymphoma (NHL)
  • Diffuse large cell B-cell lymphoma
  • Grade III follicular center-cell lymphoma
  • Primary mediastinal B-cell lymphoma



• CD20 positive



• First relapse after doxorubicin containing regimen



• Documented remission of at least 3 months after first-line chemotherapy



• No Epstein-Barr virus post-transplantation lymphoproliferative disorder



• No CNS involvement

Prior/Concurrent Therapy:

Biologic therapy:

• At least 1 month since prior immunotherapy

Chemotherapy:

• See Disease Characteristics
• At least 1 month since prior chemotherapy

Endocrine therapy:

• Not specified

Radiotherapy:

• At least 1 month since prior radiotherapy

Surgery:

• Not specified

Patient Characteristics:

Age:

• 18 to 65

Performance status:

• WHO 0-1

Life expectancy:

• Not specified

Hematopoietic:

• Not specified

Hepatic:

• No hepatic dysfunction
• Bilirubin less than 2.5 times upper limit of normal (ULN)
• Transaminases less than 2.5 times ULN

Renal:

• No renal dysfunction
• Creatinine less than 2.0 mg/dL

  OR

• Creatinine clearance greater than 40 mL/min

Cardiovascular:

• No severe cardiac dysfunction
• No New York Heart association class II-IV heart disease

Pulmonary:

• No severe pulmonary dysfunction
• Vital capacity or diffusion capacity at least 70% predicted unless related to NHL involvement

Other:

• No active uncontrolled infection
• HIV negative
• No intolerance to exogenous protein administration

Expected Enrollment

A total of 296-340 patients (148-170 per treatment arm) will be accrued for this study within 4-5 years.

Outcomes

Overall survival

Response rate
Event-free survival

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.

Vellenga E, van Putten WL, van 't Veer MB, et al.: Rituximab improves the treatment results of DHAP-VIM-DHAP and ASCT in relapsed/progressive aggressive CD20+ NHL: a prospective randomized HOVON trial. Blood 111 (2): 537-43, 2008.[PUBMED Abstract]

Trial Contact Information

Trial Lead Organizations

Commissie Voor Klinisch Toegepast Onderzoek

Edo Vellenga, MD, Protocol chair		Ph: 31-50-361-2317 Email: e.vellenga@int.umcg.nl

Belgium
	Leuven
	U.Z. Gasthuisberg
		G.E.G. Verhoef, MD, PhD	Ph:  32-16-34608
			Email: gregor.verhoef@uz.kuleuven.ac.be
Netherlands
	Amersfoort
	Meander Medisch Centrum
		M.H.H. Kramer, MD, PhD	Ph:  31-33-422-5511
	Amsterdam
	Academisch Medisch Centrum at University of Amsterdam
		M. H. J. Van Oers, MD	Ph:  31-20-566-5785
			Email: m.H.vanoers@amc.uva.nl
	Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital
		J. Baars, MD, PhD	Ph:  31-20-512-2570 or 512-2568
	Vrije Universiteit Medisch Centrum
		P. C. Huijgens, MD, PhD	Ph:  31-20-444-2604
			Email: pc.huijgens@vumc.nl
	Enschede
	Medisch Spectrum Twente
		M.R. Schaafsma, MD	Ph:  31-53-487-2444
	Groningen
	University Medical Center Groningen
		G. W. Van Imhoff, MD, PhD	Ph:  31-50-361-2354
			Email: g.w.van.imhoff@int.umcg.nl
	Leeuwarden
	Medisch Centrum Leeuwarden - Zuid
		P. Joosten, MD	Ph:  31-58-286-6965
	Leiden
	Leiden University Medical Center
		Willem Fibbe, MD, PhD	Ph:  31-71-526-5129
	Maastricht
	Academisch Ziekenhuis Maastricht
		Harry Schouten, MD, PhD	Ph:  31-43-387-7025
			Email: h.schouten@intmed.unimaas.nl
	Nieuwegein
	Sint Antonius Ziekenhuis
		D.H. Biesma, MD	Ph:  31-30-609-2088
			Email: d.biesma@antonius.net
	Nijmegen
	Universitair Medisch Centrum St. Radboud - Nijmegen
		John Raemaekers, MD, PhD	Ph:  31-24-361-4762
			Email: J.Raemaekers@hemat.umcn.nl
	Rotterdam
	Daniel Den Hoed Cancer Center at Erasmus Medical Center
		Pieter Sonneveld, MD, PhD	Ph:  31-10-439-1911
			Email: p.sonneveld@erasmusmc.nl
	's-Gravenhage
	HagaZiekenhuis - Locatie Leyenburg
		Pierre Wijermans, MD, PhD	Ph:  31-70-359-2556
			Email: pwijermans@hagaziekenhuis.nl
	's-Hertogenbosch
	Jeroen Bosch Ziekenhuis
		H. Sinnige, MD	Ph:  31 73 6162452
	Utrecht
	University Medical Center Utrecht
		Anton Hagenbeek, MD, PhD	Ph:  31-30-250-7769
			Email: a.hagenbeek@umcutrecht.nl
	Zwolle
	Isala Klinieken - locatie Sophia
		Marinus Van Marwijk Kooij, MD	Ph:  31-38-424-7039

Registry Information
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)
Trial Start Date		2000-09-01
Registered in ClinicalTrials.gov		NCT00012051
Date Submitted to PDQ		2001-01-04
Information Last Verified		2007-03-26

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