High Dose Chemotherapy With or Without Bone Marrow Transplantation in Treating Patients With Intermediate- or High-Grade Non-Hodgkin's Lymphoma

A Randomized Trial to Evaluate Early High Dose Therapy and Autologous Bone Marrow Transplantation as Part of Planned Initial Therapy for Poor Risk Intermediate/High Grade NHL

RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Bone marrow transplantation may allow doctors to give higher doses of chemotherapy drugs and kill more cancer cells. It is not yet known whether high dose chemotherapy plus bone marrow transplantation is more effective than high dose chemotherapy alone for intermediate- or high-grade non-Hodgkin's lymphoma.

PURPOSE: Randomized phase III trial to compare the effectiveness of high dose chemotherapy with or without bone marrow transplantation in treating patients who have intermediate- or high-grade non-Hodgkin's lymphoma.

Study Overview

• Status: Unknown
• Conditions: Lymphoma
• Intervention / Treatment: Drug: cyclophosphamide; Drug: prednisone; Drug: cytarabine; Drug: etoposide; Drug: vincristine sulfate; Drug: doxorubicin hydrochloride; Procedure: peripheral blood stem cell transplantation; Procedure: autologous bone marrow transplantation; Drug: melphalan; Drug: CHOP regimen; Drug: carmustine

Detailed Description

OBJECTIVES: I. Assess the value of early intensification with autologous bone marrow transplantation or stem cell support in patients with poor prognosis intermediate or high grade non-Hodgkin's lymphoma.

OUTLINE: This is a randomized, multicenter study. Patients are stratified by age (under 50 vs 50 and over), bone marrow involvement (yes vs no), and country. All patients receive cyclophosphamide, doxorubicin, and vincristine on day 1 and prednisone on days 1-5. Courses repeat every 21 days. Patients receive a minimum of 6 courses of treatment in the absence of disease progression and unacceptable toxicity. Arm I: Patients receive carmustine IV over 2 hours on day 1 in week 9 or 10. Etoposide and cytarabine IV are administered over 30 minutes on days 2-5. Melphalan IV is administered over 5 minutes on day 6. Patients receive cryopreserved bone marrow or peripheral blood stem cells on day 7. Arm II: Patients continue conventional therapy. Patients are followed at 8-9 weeks and 6 months.

PROJECTED ACCRUAL: This study will accrue 500 patients.

• Study Type: Interventional
• Enrollment (Anticipated): 500
• Phase: Phase 3

Contacts and Locations

Study Locations

• Czech Republic
  • Prague (Praha), Czech Republic, 128 08
    • Charles University Hospital
• Denmark
  • Aarhus, Denmark, DK 8000
    • Aarhus Amtssygehus
  • Copenhagen, Denmark, 2100
    • Rigshospitalet
• Norway
  • Oslo, Norway, N-0310
    • Norwegian Radium Hospital
  • Oslo, Norway, N-0407 4
    • Ullevall Hospital
  • Tromso, Norway, N-9037
    • University of Tromso
• United Kingdom
  • Bournemouth, United Kingdom, BH7 7DW
    • Royal Bournemouth Hospital
  • Carluke UK, United Kingdom, ML8 5ER
    • Law Hospital
  • Chichester, United Kingdom, P019 4SE
    • Saint Richards Hospital
  • Enfield, United Kingdom, NG31 8DG
    • Chase Farm Hospital
  • Epsom Surrey, United Kingdom, KT19 7EG
    • Epsom General Hospital
  • Grantham, United Kingdom, NG31 8DG
    • Grantham and District Hospital
  • Ilford, Essex, United Kingdom, IG3 8YB
    • King George Hospital
  • King's Lynn, United Kingdom, PE30 4ET
    • Queen Elizabeth Hospital
  • Liverpool, United Kingdom, L9 1AE
    • Walton General Hospital
  • London, United Kingdom, W2 1NY
    • St. Mary's Hospital
  • London, United Kingdom, E13 8RU
    • Newham General Hospital
  • Middlesex, United Kingdom, N18 1QZ
    • West Middlesex Hospital
  • Redhill, United Kingdom, RH1 5RH
    • East Surrey Hospital
  • Rotherham, United Kingdom, S60 2UD
    • Rotherham District General Hospital-NHS Trust
  • Scunthorpe, United Kingdom, DN15 7BH
    • Scunthorpe General Hospital
  • Stafford, United Kingdom, ST16 3SA
    • Staffordshire General Hospital
  • England
    • Aylesbury-Buckinghamshire, England, United Kingdom, HP21 8AL
      • Stoke Mandeville Hospital
    • Bath, England, United Kingdom, BA1 3NG
      • Royal United Hospital
    • Birmingham, England, United Kingdom, B18 7QH
      • City Hospital - Birmingham
    • Birmingham, England, United Kingdom, B9 5SS
      • Birmingham Heartlands and Solihull NHS Trust (Teaching)
    • Bristol, England, United Kingdom, BS2 8ED
      • Bristol Haematology and Oncology Centre
    • Bristol, England, United Kingdom, BS10 5NB
      • Southmead Hospital
    • Burton-upon-Trent, England, United Kingdom, DE14 3QH
      • Queen's Hospital, Burton
    • Canterbury, England, United Kingdom, CT2 7NR
      • Kent and Canterbury Hospital
    • Cheltenham, England, United Kingdom, GL53 7AN
      • Cheltenham General Hospital
    • Chester, England, United Kingdom, CH2 1UL
      • Countess of Chester Hospital
    • Derby, England, United Kingdom, DE1 2QY
      • Derbyshire Royal Infirmary
    • Hampstead, London, England, United Kingdom, NW3 2QG
      • Royal Free Hospital
    • Harrow, England, United Kingdom, HA1 3UJ
      • Northwick Park Hospital
    • Huddersfield, West Yorks, England, United Kingdom, HD3 3EA
      • Huddersfield Royal Infirmary
    • Ipswich, England, United Kingdom, IP4 5PD
      • Ipswich Hospital NHS Trust
    • Leeds, England, United Kingdom, LS1 3EX
      • Leeds Teaching Hospital Trust
    • Leicester, England, United Kingdom, LE1 5WW
      • University Hospitals of Leicester
    • Liverpool, England, United Kingdom, L7 8XP
      • Royal Liverpool and Broadgreen Hospitals
    • London, England, United Kingdom, EC1A 7BE
      • Saint Bartholomew's Hospital
    • London, England, United Kingdom, SW17 ORE
      • St. Georges Hospital Medical School
    • London, England, United Kingdom, W6 8RF
      • Charing Cross Hospital
    • London, England, United Kingdom, E11 1NR
      • Whipps Cross Hospital
    • London, England, United Kingdom, WIT 3AA
      • Middlesex Hospital- Meyerstein Institute
    • London, England, United Kingdom, W1W 7EJ
      • University College London
    • London, England, United Kingdom, EC1A 7BE
      • St. Bartholomew's Hospital
    • London, England, United Kingdom, W1N 8AA
      • University College London Medical School
    • Maidstone, England, United Kingdom, ME16 9QQ
      • Maidstone Hospital
    • Manchester, England, United Kingdom, M20 4BX
      • Christie Hospital N.H.S. Trust
    • Merseyside, England, United Kingdom, L63 4JY
      • Clatterbridge Centre for Oncology NHS Trust
    • Merseyside, England, United Kingdom, PR8 6NJ
      • Southport and Formby District General Hospital
    • Milton Keynes, England, United Kingdom, MK6 5LD
      • Milton Keynes General Hospital
    • Northwood, England, United Kingdom, HA6 2RN
      • Mount Vernon Hospital
    • Nottingham, England, United Kingdom, NG5 1PB
      • Nottingham City Hospital NHS Trust
    • Oxford, England, United Kingdom, 0X3 9DU
      • Oxford Radcliffe Hospital
    • Plymouth, England, United Kingdom, PL6 8DH
      • Derriford Hospital
    • Romford, England, United Kingdom, RM7 OBE
      • Oldchurch Hospital
    • Royal Tunbridge Wells, Kent, England, United Kingdom, TN2 4QJ
      • Pembury Hospital
    • Sheffield, England, United Kingdom, S1O 2SJ
      • Weston Park Hospital
    • Sheffield, England, United Kingdom, S1O 2JF
      • Sheffield Teaching Hospitals
    • Southampton, England, United Kingdom, SO14 0YG
      • Royal South Hants Hospital
    • Sutton, England, United Kingdom, SM2 5PT
      • Royal Marsden Hospital
    • Torquay Devon, England, United Kingdom, TQ2 7AA
      • Torbay Hospital
    • Uxbridge, England, United Kingdom, UB8 3NN
      • Hillingdon Hospital
    • West Bromwich, England, United Kingdom
      • Sandwell District General Hospital
    • West Midlands, England, United Kingdom, B75 7RR
      • Good Hope Hospital Trust
    • West Yorks, England, United Kingdom, WF8 1PL
      • Pontefract General Infirmary
    • Wolverhampton, England, United Kingdom, WV10 0QP
      • New Cross Hospital
  • Northern Ireland
    • Belfast, Northern Ireland, United Kingdom, BT9 7AB
      • Belfast City Hospital Trust
    • Londonderry, Northern Ireland, United Kingdom, BT47 1SB
      • Altnagelvin Area Hospital
  • Wales
    • Bangor, Wales, United Kingdom, LL57 2PW
      • Ysbyty Gwynedd

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 65 years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

DISEASE CHARACTERISTICS: Histologically confirmed intermediate or high grade adult non-Hodgkin's lymphoma: Follicular large cell lymphoma Diffuse mixed cell lymphoma Diffuse large cell lymphoma Diffuse immunoblastic lymphoma Poor prognostic features defined as the presence of 2 or 3 of the following: Stage III/IV Lactase dehydrogenase greater than normal ECOG performance status 2-4 A new classification scheme for adult non-Hodgkin's lymphoma has been adopted by PDQ. The terminology of "indolent" or "aggressive" lymphoma will replace the former terminology of "low", "intermediate", or "high" grade lymphoma. However, this protocol uses the former terminology.

PATIENT CHARACTERISTICS: Age: 16 to 65 Performance status: See Disease Characteristics Life expectancy: Not specified Hematopoietic: Not specified Hepatic: See Disease Characteristics Renal: Not specified Other: No other medical condition prohibiting intensive therapy

PRIOR CONCURRENT THERAPY: At least 5 years since prior systemic therapy for cancer

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized

Collaborators and Investigators

• Sponsor: Lymphoma Trials Office
• Investigators: Study Chair: David C. Linch, University College London Hospitals

Study record dates

Study Major Dates

• Study Start: January 1, 1993

Study Registration Dates

• First Submitted: November 1, 1999
• First Submitted That Met QC Criteria: January 26, 2004
• First Posted (Estimate): January 27, 2004

Study Record Updates

• Last Update Posted (Estimate): September 20, 2013
• Last Update Submitted That Met QC Criteria: September 19, 2013
• Last Verified: May 1, 2007

More Information

Terms related to this study

• Keywords: stage III adult diffuse large cell lymphoma; stage III adult immunoblastic large cell lymphoma; stage IV grade 3 follicular lymphoma; stage IV adult diffuse large cell lymphoma; stage IV adult immunoblastic large cell lymphoma; stage III grade 3 follicular lymphoma; stage III adult diffuse mixed cell lymphoma; stage IV adult diffuse mixed cell lymphoma
• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Lymphoma; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Enzyme Inhibitors; Anti-Inflammatory Agents; Antirheumatic Agents; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Antineoplastic Agents, Alkylating; Alkylating Agents; Myeloablative Agonists; Antineoplastic Agents, Phytogenic; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Antibiotics, Antineoplastic; Cyclophosphamide; Etoposide; Prednisone; Melphalan; Doxorubicin; Liposomal doxorubicin; Cytarabine; Vincristine; Carmustine
• Other Study ID Numbers: CDR0000066645; BNLI-LY02; EU-98039