Combination Chemotherapy Plus Peripheral Stem Cell Transplantation With or Without Rituximab in Treating Patients With Relapsed Non-Hodgkin's Lymphoma

This study has been completed.
Sponsor:
Collaborator:
Lymphoma Trials Office
Information provided by:
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00005589
First received: May 2, 2000
Last updated: September 16, 2013
Last verified: March 2007
  Purpose

RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Peripheral stem cell transplantation may allow the doctor to give higher doses of chemotherapy drugs and kill more cancer cells. Monoclonal antibodies such as rituximab can locate cancer cells and either kill them or deliver cancer-killing substances to them without harming normal cells. It is not yet known if combination chemotherapy plus peripheral stem cell transplantation is more effective with or without rituximab for non-Hodgkin's lymphoma.

PURPOSE: This randomized phase III trial is studying giving combination chemotherapy and peripheral stem cell transplantation together with rituximab to see how well it works compared to combination chemotherapy and peripheral stem cell transplantation alone in treating patients with relapsed non-Hodgkin's lymphoma.


Condition Intervention Phase
Lymphoma
Biological: filgrastim
Biological: rituximab
Drug: carmustine
Drug: cyclophosphamide
Drug: cytarabine
Drug: etoposide
Drug: melphalan
Procedure: bone marrow ablation with stem cell support
Procedure: peripheral blood stem cell transplantation
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Masking: Open Label
Primary Purpose: Treatment
Official Title: Randomized Study of Rituximab (Mabthera) in Patients With Relapsed Follicular Lymphoma Prior to High-Dose Therapy as In Vivo Purging and to Maintain Remission Following High-Dose Therapy

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Time to disease progression [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Response rate and survival [ Designated as safety issue: No ]
  • Molecular remission rates [ Designated as safety issue: No ]
  • Safety [ Designated as safety issue: Yes ]

Estimated Enrollment: 460
Study Start Date: October 1999
Study Completion Date: April 2013
Detailed Description:

OBJECTIVES:

  • Determine the effects of in vivo rituximab purging and maintenance on progression-free survival in patients with relapsed or resistant follicular non-Hodgkin's lymphoma undergoing high-dose chemotherapy.
  • Determine the effects of this regimen on response rate and overall survival in this patient population.
  • Determine the effects of in vivo purging with rituximab on molecular remission rates in the hematopoietic product and the patients.
  • Determine the safety of rituximab in the transplant setting.

OUTLINE: This is a randomized, open-label, multicenter study. Patients are stratified according to type of remission (complete vs good partial) and which remission (second vs third). Patients are randomized to one of four treatment arms.

All patients receive induction chemotherapy comprising cyclophosphamide IV over 3-4 hours on day 0 or a standard induction chemotherapy regimen. Filgrastim (G-CSF) is administered subcutaneously daily beginning on day 1.

Patients are then randomized to receive either in vivo rituximab purging or no purging following restaging after completion of induction. For those patients receiving purging (arms I and II), rituximab is administered IV once weekly for 4 weeks.

Peripheral blood stem cells (PBSC) are collected between days 8 and 12 post induction chemotherapy. Within 4 weeks of PBSC collection, patients receive carmustine IV over 2 hours on day -6, etoposide IV over 2 hours on days -5 to -2, cytarabine IV over 5 minutes twice daily on days -5 to -2, and melphalan IV over 10-15 minutes on day -1. (Alternatively, high dose cyclophosphamide and total body irradiation beginning 2-4 weeks after cyclophosphamide or standard induction chemotherapy priming is also allowed.) PBSC are reinfused on day 0.

Patients are further randomized to receive either rituximab maintenance or observation only. For those patients receiving maintenance (arms I and III), rituximab is administered IV once every 2 months for 4 doses beginning 30 days after PBSC reinfusion.

Patients are followed at 30 days, 3, 6, 9, and 12 months after PBSC transplant, every 6 months for 2 years, and then annually thereafter.

PROJECTED ACCRUAL: A total of 460 patients (115 per treatment arm) will be accrued for this study within 5 years.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

DISEASE CHARACTERISTICS:

  • Relapsed or resistant follicular non-Hodgkin's lymphoma (NHL)

    • No evidence of transformation to high grade or diffuse large B-cell NHL
  • CD20 positive with no evidence of transformation
  • Achievement of complete remission (CR) or very good partial remission (VGPR) following reinduction chemotherapy with any standard regimen

    • Includes patients who fail to respond to first-line chemotherapy but who achieve CR or VGPR after proceeding directly to second-line chemotherapy
  • Platelet count greater than 100,000/mm^3 after induction chemotherapy and before randomization
  • No CNS involvement

PATIENT CHARACTERISTICS:

Age:

  • 18 and over

Performance status:

  • WHO 0-1

Life expectancy:

  • Not specified

Hematopoietic:

  • See Disease Characteristics

Hepatic:

  • Bilirubin normal
  • ALT no greater than 2 times upper limit of normal (ULN)
  • Alkaline phosphatase no greater than 2 times ULN
  • Hepatitis B negative
  • Hepatitis C negative

Renal:

  • Creatinine no greater than 2 times ULN
  • BUN no greater than 2 times ULN

Cardiovascular:

  • No inadequate cardiac function

Pulmonary:

  • No inadequate pulmonary function

Other:

  • Not pregnant or nursing
  • HIV negative
  • No other uncontrolled serious medical conditions
  • No other malignancy within the past 5 years except nonmelanoma skin tumors or carcinoma in situ of the cervix

PRIOR CONCURRENT THERAPY:

Biologic therapy:

  • More than 12 months since prior CD20 therapy, including rituximab
  • No prior peripheral blood stem cell transplantation

Chemotherapy:

  • See Disease Characteristics
  • No more than 3 prior chemotherapy regimens for NHL

Endocrine therapy:

  • Not specified

Radiotherapy:

  • No prior radiotherapy to greater than 30% of bone marrow

Surgery:

  • Not specified
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00005589

  Hide Study Locations
Locations
Australia, New South Wales
Sydney Cancer Centre at Royal Prince Alfred Hospital
Sydney, New South Wales, Australia, 2050
Westmead Institute for Cancer Research at Westmead Hospital
Westmead, New South Wales, Australia, 2145
Australia, Queensland
Royal Brisbane and Women's Hospital
Brisbane, Queensland, Australia, 4029
Australia, South Australia
Royal Adelaide Hospital Cancer Centre
Adelaide, South Australia, Australia, 5000
Queen Elizabeth Hospital
Woodville, South Australia, Australia, 5011
Australia, Victoria
Royal Melbourne Hospital
Parkville, Victoria, Australia, 3050
Australia, Western Australia
Fremantle Hospital
Fremantle, Western Australia, Australia, 6160
Royal Perth Hospital
Perth, Western Australia, Australia, 6000
Austria
Allgemeines Krankenhaus - Universitatskliniken
Vienna, Austria, A-1090
Belgium
Ziekenhuis Netwerk Antwerpen Middelheim
Antwerpen, Belgium, B-2020
Academisch Ziekenhuis der Vrije Universiteit Brussel
Brussels, Belgium, 1090
Institut Jules Bordet
Brussels, Belgium, 1000
Universitair Ziekenhuis Gent
Ghent, Belgium, B-9000
U.Z. Gasthuisberg
Leuven, Belgium, B-3000
CHU Liege - Domaine Universitaire du Sart Tilman
Liege, Belgium, B-4000
Clinique Universitaire De Mont-Godinne
Mont-Godinne Yvoir, Belgium, 5530
H. Hartziekenhuis - Roeselaere.
Roeselaere, Belgium, 8800
Canada, Alberta
Tom Baker Cancer Centre - Calgary
Calgary, Alberta, Canada, T2N 4N2
Canada, Ontario
Ottawa Hospital Regional Cancer Centre - General Campus
Ottawa, Ontario, Canada, K1H 8L6
Czech Republic
University Hospital Kralovske Vinohr
Prague, Czech Republic, 10034
Denmark
Aalborg Hospital
Aalborg, Denmark, DK-9000
Rigshospitalet - Copenhagen University Hospital
Copenhagen, Denmark, 2100
Odense University Hospital
Odense, Denmark, DK-5000
France
Centre Hospitalier Regional et Universitaire d'Angers
Angers, France, 49033
Polyclinique Du Parc
Caen, France, 14052
Centre Regional Francois Baclesse
Caen, France, 14076
CHU de Grenoble - Hopital de la Tronche
Grenoble, France, 38043
Centre Leon Berard
Lyon, France, 69373
Polyclinique Saint Jean
Melun, France, 77000
Centre Regional de Lutte Contre le Cancer - Centre Val d'Aurelle
Montpellier, France, 34298
CHR Hotel Dieu
Nantes, France, 44093
Hopital Saint-Louis
Paris, France, 75475
CHU Pitie-Salpetriere
Paris, France, 75651
Centre Hospitalier Lyon Sud
Pierre Benite, France, 69495
Centre Hospitalier Universitaire de Rennes
Rennes, France, 35033
Centre Henri Becquerel
Rouen, France, 76038
Centre Hospitalier Universitaire Bretonneau de Tours
Tours, France, 37044
Institut Gustave Roussy
Villejuif, France, F-94805
Germany
Klinikum Augsburg
Augsburg, Germany, DOH-86156
DIAKO Ev. Diakonie Krankenhaus gGmbH
Bremen, Germany, D-28239
Universitaetsklinikum Goettingen
Goettingen, Germany, D-37075
Asklepios Klinik St. Georg
Hamburg, Germany, D-20099
Universitaetsklinikum des Saarlandes
Homburg, Germany, D-66424
Medical University Hospital Homburg
Homburg, Germany, 66421
Klinikum Nuernberg - Klinikum Nord
Nuernberg, Germany, D-90419
Klinikum Oldenburg
Oldenburg, Germany, D-26133
Southwest German Cancer Center at Eberhard-Karls-University
Tuebingen, Germany, D-72076
Israel
Chaim Sheba Medical Center
Tel Hashomer, Israel, 52621
New Zealand
Auckland City Hospital
Auckland, New Zealand, 1
Canterbury Health Laboratories
Christchurch, New Zealand
Waikato Hospital
Hamilton, New Zealand, 2020
Poland
Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology
Warsaw, Poland, 02-781
K. Dluski Hospital-Medical Academy
Wroclaw, Poland, 53 439
Portugal
Instituto Portugues de Oncologia de Francisco Gentil - Centro Regional de Oncologia de Lisboa, S.A.
Lisboa, Portugal, 1099-023 Codex
Spain
Hospital General - Alicante
Alicante, Spain, 3010
Hospital de Cruces
Barakaldo Bilbao, Spain, E-48903
Hospital Clinic de Barcelona
Barcelona, Spain, 08036
Hospital Universitari Germans Trias i Pujol
Barcelona, Spain, 08916
Centro Medico Teknon
Barcelona, Spain, 08022
Hospital de la Santa Cruz i Sant Pau
Barcelona, Spain, 08025
Hospital San Pedro de Alcantara
Caceres, Spain, 10000
Hospital Universitario Puerta Del Mar
Cadiz, Spain, 11000
Hospital General de Castellon
Castellon, Spain, 12004
Hospital Virgen de la Arrixaca
El Palmar, Spain, 30120
Hospital de Galdakao
Galdakao Vizcaya, Spain, 48000
Hospital Virgen de las Nieves
Granada, Spain, 18014
Hospital Cuidad de Jaen
Jaen, Spain, E-23006
Hospital Juan Canalejo
La Coruna, Spain, 15000
Hospital de Gran Canaria Dr. Negrin
Las Palmas de Gran Canaria, Spain, 350311
Hospital Universitario 12 de Octubre
Madrid, Spain, 28041
Hospital General Universitario Gregorio Maranon
Madrid, Spain, 28007
Hospital Ramon y Cajal
Madrid, Spain, 28034
Hospital Universitario San Carlos
Madrid, Spain, 28040
Hospital de la Princesa
Madrid, Spain, 28006
Hospital Universitario de Getafe
Madrid, Spain, 28905
Hospital General Universitario Morales Meseguer
Murcia, Spain, 30008
Hospital Universitario Central de Asturias
Oviedo, Spain, 33006
Hospital Son Dureta
Palma De Mallorca, Spain, 07014
University Hospital - Salamanca
Salamanca, Spain, 37007
Hospital Virgen de la Vega
Salamanca, Spain, 37007
Hospital Universitario Marques de Valdecilla
Santander, Spain, 39008
Hospital Universidad Virgen Del Rocio
Sevilla, Spain, E- 41013
Hospital Mutua de Terrassa
Terrassa, Spain, 08221
Hospital Clinico Universitario de Valencia
Valencia, Spain, 46010
Unidad De Oncol/Hemat. Hospital
Valencia, Spain, 46017
Complexo Hospitalario Xeral de Vigo
Vigo Pontevedra, Spain, 36204
Hospital Clinico Universitario Lozano Blesa
Zaragoza, Spain, 50006
Hospital Universitario Miguel Servet
Zaragoza, Spain, 50009
Sweden
Karolinska University Hospital - Huddinge
Stockholm, Sweden, SE-141 86
Switzerland
Kantonsspital Bruderholz
Bruderholz, Switzerland, CH-4101
UniversitaetsSpital Zuerich
Zurich, Switzerland, CH-8091
Turkey
Ibn-i Sina Hospital
Ankara, Turkey, 06100
United Kingdom
Stoke Mandeville Hospital
Aylesbury-Buckinghamshire, England, United Kingdom, HP21 8AL
Royal United Hospital
Bath, England, United Kingdom, BA1 3NG
Birmingham Heartlands Hospital
Birmingham, England, United Kingdom, B9 5SS
Royal Bournemouth Hospital
Bournemouth, England, United Kingdom, BH7 7DW
Bristol Haematology and Oncology Centre
Bristol, England, United Kingdom, BS2 8ED
Royal Devon and Exeter Hospital
Exeter, England, United Kingdom, EX2 5DW
Huddersfield Royal Infirmary
Huddersfield, West Yorks, England, United Kingdom, HD3 3EA
Hull Royal Infirmary
Hull, England, United Kingdom, HU3 2KZ
Kettering General Hosptial
Kettering, Northants, England, United Kingdom, NNI6 8UZ
Clinical Trials and Research Unit of the University of Leeds
Leeds, England, United Kingdom, LS2 9N9
Leicester Royal Infirmary
Leicester, England, United Kingdom, LE1 5WW
Liverpool University Hospital
Liverpool, England, United Kingdom, L9 7AL
Royal Liverpool and Broadgreen Hospitals NHS Trust
Liverpool, England, United Kingdom, L7 8XP
St. Georges, University of London
London, England, United Kingdom, SW17 ORE
University College Hospital - London
London, England, United Kingdom, WC1E 6AU
Middlesex Hospital
London, England, United Kingdom, WC1E 6HX
Saint Bartholomew's Hospital
London, England, United Kingdom, EC1A 7BE
St. Thomas' Hospital
London, England, United Kingdom, SE1 7EH
Clinique Sainte Elisabeth
London, England, United Kingdom, SW17 ORE
James Paget Hospital
Norfolk, England, United Kingdom, NR31 6LA
Nottingham City Hospital NHS Trust
Nottingham, England, United Kingdom, NG5 1PB
Oxford Radcliffe Hospital
Oxford, England, United Kingdom, 0X3 9DU
Pontefract General Infirmary
Pontefract West Yorkshire, England, United Kingdom, WF8 1PL
Rotherham District General Hospital - NHS Trust
Rotherham, England, United Kingdom, S60 2UD
Cancer Research Centre at Weston Park Hospital
Sheffield, England, United Kingdom, S1O 2SJ
Southampton University Hospital NHS Trust
Southampton, England, United Kingdom, SO16 6YD
Staffordshire General Hospital
Stafford, England, United Kingdom, ST16 3SA
Royal Marsden NHS Foundation Trust - Surrey
Sutton, England, United Kingdom, SM2 5PT
Princess Margaret Hospital
Swindon, England, United Kingdom, SN3 6BB
Great Western Hospital
Swindon, England, United Kingdom, SN3 6BB
Hillingdon Hospital
Uxbridge, England, United Kingdom, UB8 3NN
Sandwell General Hospital
West Bromwich, England, United Kingdom, B71 4HJ
Centre for Cancer Research and Cell Biology at Belfast City Hospital
Belfast, Northern Ireland, United Kingdom, BT9 7AB
Aberdeen Royal Infirmary
Aberdeen, Scotland, United Kingdom, AB25 2ZN
Royal Infirmary - Castle
Glasgow, Scotland, United Kingdom, G4 0SF
Pinderfields Hospital NHS Trust
Wakefield, Scotland, United Kingdom, WF1 4DG
Ysbyty Gwynedd
Bangor, Wales, United Kingdom, LL57 2PW
Prince Philip Hospital
Dyfed, Wales, United Kingdom, SA14 8QF
Singleton Hospital of the Swansea NHS Trust
Swansea, Wales, United Kingdom, SA2 8QA
Sponsors and Collaborators
EBMT Solid Tumors Working Party
Lymphoma Trials Office
Investigators
Study Chair: Ruth Pettengell, MD St George's, University of London
Study Chair: David C. Linch Middlesex Hospital
  More Information

Additional Information:
No publications provided by National Cancer Institute (NCI)

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
ClinicalTrials.gov Identifier: NCT00005589     History of Changes
Other Study ID Numbers: CDR0000067665, EBMT-EBMTLYM1, BNLI-EBMT-EBMTLYM1, EU-99050
Study First Received: May 2, 2000
Last Updated: September 16, 2013
Health Authority: United States: Federal Government

Keywords provided by National Cancer Institute (NCI):
recurrent grade 1 follicular lymphoma
recurrent grade 2 follicular lymphoma
recurrent grade 3 follicular lymphoma

Additional relevant MeSH terms:
Lymphoma
Lymphoma, Follicular
Lymphoma, Non-Hodgkin
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Carmustine
Cyclophosphamide
Melphalan
Rituximab
Cytarabine
Etoposide
Lenograstim
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Myeloablative Agonists
Antimetabolites, Antineoplastic
Antimetabolites
Antiviral Agents

ClinicalTrials.gov processed this record on April 17, 2014