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

Lymphoma Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00005589
• Other study ID #: CDR0000067665
• Secondary ID: EBMT-EBMTLYM1BNL
• Status: Completed
• Phase: Phase 3
• First received: May 2, 2000
• Last updated: September 16, 2013
• Start date: October 1999
• Est. completion date: April 2013

Study information

• Verified date: March 2007
• Source: National Cancer Institute (NCI)
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal Government
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 460
• Est. completion date: April 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Allocation: Randomized, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Lymphoma
• Lymphoma, Follicular

Intervention

Biological:
• filgrastim

• rituximab

Drug:
• carmustine

• cyclophosphamide

• cytarabine

• etoposide

• melphalan

Procedure:
• bone marrow ablation with stem cell support

• peripheral blood stem cell transplantation

Locations

Country	Name	City	State
Australia	Royal Adelaide Hospital Cancer Centre	Adelaide	South Australia
Australia	Royal Brisbane and Women's Hospital	Brisbane	Queensland
Australia	Fremantle Hospital	Fremantle	Western Australia
Australia	Royal Melbourne Hospital	Parkville	Victoria
Australia	Royal Perth Hospital	Perth	Western Australia
Australia	Sydney Cancer Centre at Royal Prince Alfred Hospital	Sydney	New South Wales
Australia	Westmead Institute for Cancer Research at Westmead Hospital	Westmead	New South Wales
Australia	Queen Elizabeth Hospital	Woodville	South Australia
Austria	Allgemeines Krankenhaus - Universitatskliniken	Vienna
Belgium	Ziekenhuis Netwerk Antwerpen Middelheim	Antwerpen
Belgium	Academisch Ziekenhuis der Vrije Universiteit Brussel	Brussels
Belgium	Institut Jules Bordet	Brussels
Belgium	Universitair Ziekenhuis Gent	Ghent
Belgium	U.Z. Gasthuisberg	Leuven
Belgium	CHU Liege - Domaine Universitaire du Sart Tilman	Liege
Belgium	Clinique Universitaire De Mont-Godinne	Mont-Godinne Yvoir
Belgium	H. Hartziekenhuis - Roeselaere.	Roeselaere
Canada	Tom Baker Cancer Centre - Calgary	Calgary	Alberta
Canada	Ottawa Hospital Regional Cancer Centre - General Campus	Ottawa	Ontario
Czech Republic	University Hospital Kralovske Vinohr	Prague
Denmark	Aalborg Hospital	Aalborg
Denmark	Rigshospitalet - Copenhagen University Hospital	Copenhagen
Denmark	Odense University Hospital	Odense
France	Centre Hospitalier Regional et Universitaire d'Angers	Angers
France	Centre Regional Francois Baclesse	Caen
France	Polyclinique Du Parc	Caen
France	CHU de Grenoble - Hopital de la Tronche	Grenoble
France	Centre Leon Berard	Lyon
France	Polyclinique Saint Jean	Melun
France	Centre Regional de Lutte Contre le Cancer - Centre Val d'Aurelle	Montpellier
France	CHR Hotel Dieu	Nantes
France	CHU Pitie-Salpetriere	Paris
France	Hopital Saint-Louis	Paris
France	Centre Hospitalier Lyon Sud	Pierre Benite
France	Centre Hospitalier Universitaire de Rennes	Rennes
France	Centre Henri Becquerel	Rouen
France	Centre Hospitalier Universitaire Bretonneau de Tours	Tours
France	Institut Gustave Roussy	Villejuif
Germany	Klinikum Augsburg	Augsburg
Germany	DIAKO Ev. Diakonie Krankenhaus gGmbH	Bremen
Germany	Universitaetsklinikum Goettingen	Goettingen
Germany	Asklepios Klinik St. Georg	Hamburg
Germany	Medical University Hospital Homburg	Homburg
Germany	Universitaetsklinikum des Saarlandes	Homburg
Germany	Klinikum Nuernberg - Klinikum Nord	Nuernberg
Germany	Klinikum Oldenburg	Oldenburg
Germany	Southwest German Cancer Center at Eberhard-Karls-University	Tuebingen
Israel	Chaim Sheba Medical Center	Tel Hashomer
New Zealand	Auckland City Hospital	Auckland
New Zealand	Canterbury Health Laboratories	Christchurch
New Zealand	Waikato Hospital	Hamilton
Poland	Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology	Warsaw
Poland	K. Dluski Hospital-Medical Academy	Wroclaw
Portugal	Instituto Portugues de Oncologia de Francisco Gentil - Centro Regional de Oncologia de Lisboa, S.A.	Lisboa
Spain	Hospital General - Alicante	Alicante
Spain	Hospital de Cruces	Barakaldo Bilbao
Spain	Centro Medico Teknon	Barcelona
Spain	Hospital Clinic de Barcelona	Barcelona
Spain	Hospital de la Santa Cruz i Sant Pau	Barcelona
Spain	Hospital Universitari Germans Trias i Pujol	Barcelona
Spain	Hospital San Pedro de Alcantara	Caceres
Spain	Hospital Universitario Puerta Del Mar	Cadiz
Spain	Hospital General de Castellon	Castellon
Spain	Hospital Virgen de la Arrixaca	El Palmar
Spain	Hospital de Galdakao	Galdakao Vizcaya
Spain	Hospital Virgen de las Nieves	Granada
Spain	Hospital Cuidad de Jaen	Jaen
Spain	Hospital Juan Canalejo	La Coruna
Spain	Hospital de Gran Canaria Dr. Negrin	Las Palmas de Gran Canaria
Spain	Hospital de la Princesa	Madrid
Spain	Hospital General Universitario Gregorio Maranon	Madrid
Spain	Hospital Ramon y Cajal	Madrid
Spain	Hospital Universitario 12 de Octubre	Madrid
Spain	Hospital Universitario de Getafe	Madrid
Spain	Hospital Universitario San Carlos	Madrid
Spain	Hospital General Universitario Morales Meseguer	Murcia
Spain	Hospital Universitario Central de Asturias	Oviedo
Spain	Hospital Son Dureta	Palma De Mallorca
Spain	Hospital Virgen de la Vega	Salamanca
Spain	University Hospital - Salamanca	Salamanca
Spain	Hospital Universitario Marques de Valdecilla	Santander
Spain	Hospital Universidad Virgen Del Rocio	Sevilla
Spain	Hospital Mutua de Terrassa	Terrassa
Spain	Hospital Clinico Universitario de Valencia	Valencia
Spain	Unidad De Oncol/Hemat. Hospital	Valencia
Spain	Complexo Hospitalario Xeral de Vigo	Vigo Pontevedra
Spain	Hospital Clinico Universitario Lozano Blesa	Zaragoza
Spain	Hospital Universitario Miguel Servet	Zaragoza
Sweden	Karolinska University Hospital - Huddinge	Stockholm
Switzerland	Kantonsspital Bruderholz	Bruderholz
Switzerland	UniversitaetsSpital Zuerich	Zurich
Turkey	Ibn-i Sina Hospital	Ankara
United Kingdom	Aberdeen Royal Infirmary	Aberdeen	Scotland
United Kingdom	Stoke Mandeville Hospital	Aylesbury-Buckinghamshire	England
United Kingdom	Ysbyty Gwynedd	Bangor	Wales
United Kingdom	Royal United Hospital	Bath	England
United Kingdom	Centre for Cancer Research and Cell Biology at Belfast City Hospital	Belfast	Northern Ireland
United Kingdom	Birmingham Heartlands Hospital	Birmingham	England
United Kingdom	Royal Bournemouth Hospital	Bournemouth	England
United Kingdom	Bristol Haematology and Oncology Centre	Bristol	England
United Kingdom	Prince Philip Hospital	Dyfed	Wales
United Kingdom	Royal Devon and Exeter Hospital	Exeter	England
United Kingdom	Royal Infirmary - Castle	Glasgow	Scotland
United Kingdom	Huddersfield Royal Infirmary	Huddersfield, West Yorks	England
United Kingdom	Hull Royal Infirmary	Hull	England
United Kingdom	Kettering General Hosptial	Kettering, Northants	England
United Kingdom	Clinical Trials and Research Unit of the University of Leeds	Leeds	England
United Kingdom	Leicester Royal Infirmary	Leicester	England
United Kingdom	Liverpool University Hospital	Liverpool	England
United Kingdom	Royal Liverpool and Broadgreen Hospitals NHS Trust	Liverpool	England
United Kingdom	Clinique Sainte Elisabeth	London	England
United Kingdom	Middlesex Hospital	London	England
United Kingdom	Saint Bartholomew's Hospital	London	England
United Kingdom	St. Georges, University of London	London	England
United Kingdom	St. Thomas' Hospital	London	England
United Kingdom	University College Hospital - London	London	England
United Kingdom	James Paget Hospital	Norfolk	England
United Kingdom	Nottingham City Hospital NHS Trust	Nottingham	England
United Kingdom	Oxford Radcliffe Hospital	Oxford	England
United Kingdom	Pontefract General Infirmary	Pontefract West Yorkshire	England
United Kingdom	Rotherham District General Hospital - NHS Trust	Rotherham	England
United Kingdom	Cancer Research Centre at Weston Park Hospital	Sheffield	England
United Kingdom	Southampton University Hospital NHS Trust	Southampton	England
United Kingdom	Staffordshire General Hospital	Stafford	England
United Kingdom	Royal Marsden NHS Foundation Trust - Surrey	Sutton	England
United Kingdom	Singleton Hospital of the Swansea NHS Trust	Swansea	Wales
United Kingdom	Great Western Hospital	Swindon	England
United Kingdom	Princess Margaret Hospital	Swindon	England
United Kingdom	Hillingdon Hospital	Uxbridge	England
United Kingdom	Pinderfields Hospital NHS Trust	Wakefield	Scotland
United Kingdom	Sandwell General Hospital	West Bromwich	England

Sponsors (2)

Lead Sponsor	Collaborator
EBMT Solid Tumors Working Party	Lymphoma Trials Office

Countries where clinical trial is conducted

Australia,  Austria,  Belgium,  Canada,  Czech Republic,  Denmark,  France,  Germany,  Israel,  New Zealand,  Poland,  Portugal,  Spain,  Sweden,  Switzerland,  Turkey,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Time to disease progression			No
Secondary	Response rate and survival			No
Secondary	Molecular remission rates			No
Secondary	Safety			Yes