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 doctors to give higher doses of chemotherapy drugs and kill more cancer cells. It is not yet known which combination chemotherapy regimen given before peripheral stem cell transplantation is more effective in treating relapsed Hodgkin's lymphoma.

PURPOSE: Randomized phase III trial to compare different combination chemotherapy regimens followed by peripheral stem cell transplantation in treating patients who have relapsed Hodgkin's lymphoma.

Condition	Treatment or Intervention	Phase
recurrent adult Hodgkin's lymphoma	Drug: carmustine  Drug: cisplatin  Drug: cyclophosphamide  Drug: cytarabine  Drug: dexamethasone  Drug: etoposide  Drug: filgrastim  Drug: melphalan  Drug: methotrexate  Drug: vincristine  Procedure: biological response modifier therapy  Procedure: bone marrow ablation with stem cell support  Procedure: chemotherapy  Procedure: colony-stimulating factor therapy  Procedure: cytokine therapy  Procedure: high-dose chemotherapy  Procedure: peripheral blood stem cell transplantation	Phase III

Further Study Details: 

OBJECTIVES:

• Compare the efficacy of induction chemotherapy followed by combination chemotherapy and autologous peripheral blood stem cell transplantation with or without high-dose sequential chemotherapy in terms of freedom from treatment failure in patients with relapsed Hodgkin's lymphoma.
• Compare the toxicity of these regimens in these patients.
• Compare the complete remission/unconfirmed complete remission rate at 3 months, relapse-free survival, and overall survival of patients treated with these regimens.
• Compare the frequency of severe toxic effects and secondary neoplasia in patients treated with these regimens.

OUTLINE: This is a randomized, multicenter study. Patients are stratified according to participating center, type of relapse (early first relapse [remission duration 3-12 months] vs late first relapse [remission duration more than 12 months] vs second relapse without prior high-dose chemotherapy salvage [remission duration after salvage at least 3 months]), disease status at relapse (stage I or II vs stage III or IV), age (18 to 49 vs 50 to 60), and response after 2 courses of study induction chemotherapy (complete remission vs partial remission vs no change).

All patients receive induction chemotherapy comprising dexamethasone IV over 30 minutes on days 1-4 and 15-18, cisplatin IV continuously over 24 hours on days 1 and 15, cytarabine IV over 3 hours every 12 hours on days 2 and 16, and filgrastim (G-CSF) subcutaneously (SC) once daily on days 5-12 and days 19-26. Patients with complete remission (CR), unconfirmed CR, partial remission, or no change are randomized to one of two treatment arms.

• Arm I: Patients receive BEAM chemotherapy comprising carmustine IV over 30 minutes and melphalan IV over 30 minutes on day 37 and etoposide IV over 30 minutes every 12 hours and cytarabine IV over 30 minutes every 12 hours on days 37-40. Patients also receive G-CSF SC twice daily beginning on day 41 and continuing until blood counts recover. Autologous peripheral blood stem cells (PBSCs) are reinfused on day 42.
• Arm II: Patients receive high-dose cyclophosphamide IV over 8 hours on day 37, high-dose methotrexate IV over 6 hours and high-dose vincristine IV on day 51, and high-dose etoposide IV over 8 hours on days 58-61. Patients then receive BEAM chemotherapy comprising carmustine IV over 30 minutes and melphalan IV over 30 minutes on day 80 and etoposide IV over 30 minutes every 12 hours and cytarabine IV over 30 minutes every 12 hours on days 80-83. Patients also receive G-CSF SC once on days 38 and 62 and twice daily beginning on day 84 and continuing until blood counts recover. Autologous PBSCs are reinfused on day 85. Patients with residual lymphoma at 100 days after completion of BEAM chemotherapy may receive radiotherapy.

Patients are followed at 100 days after PBSC transplantation, every 3 months for 2 years, every 6 months for 2 years, and then annually thereafter.

PROJECTED ACCRUAL: A minimum of 220 patients (110 per treatment arm) will be accrued for this study within 5 years.

Ages Eligible for Study:  18 Years   -   60 Years,  Genders Eligible for Study:  Both

Criteria

DISEASE CHARACTERISTICS:

• Histologically confirmed Hodgkin's lymphoma
• Early or late first relapse
• Complete or partial remission for at least 3 months after completion of prior COPP/ABVD, COPP/ABV/IMEP, MOPP/ABV, ABVD, BEACOPP, or other polychemotherapy regimen with or without radiotherapy
• No prior salvage therapy OR
• Second relapse
• Any prior salvage therapy
• No prior high-dose chemotherapy

PATIENT CHARACTERISTICS: Age:

• 18 to 60

Performance status:

• Karnofsky 70-100% OR
• ECOG 0-2

Life expectancy:

• More than 3 months with treatment

Hematopoietic:

• Absolute neutrophil count at least 2,500/mm^3
• Platelet count at least 100,000/mm^3

Hepatic:

• Not specified

Renal:

• Creatinine clearance at least 60 mL/min

Cardiovascular:

• No uncontrolled hypertension (diastolic blood pressure greater than 115 mm Hg)
• No unstable angina
• No New York Heart Association class III or IV heart disease (congestive heart failure)
• No myocardial infarction within the past 6 months
• No uncontrolled atrial or ventricular cardiac arrhythmias

Pulmonary:

• No chronic pulmonary disease

Other:

• Not pregnant or nursing
• Fertile patients must use effective contraception
• HIV negative
• No active infection
• No poorly controlled diabetes
• No cerebral disorder
• No other concurrent malignancy except adequately treated basal cell skin cancer or cervical intraepithelial neoplasia
• No significant non-malignant disease
• No psychiatric, addictive, or other disorder that would preclude study compliance

PRIOR CONCURRENT THERAPY: Biologic therapy:

• Not specified

Chemotherapy:

• See Disease Characteristics
• No other concurrent chemotherapy

Endocrine therapy:

• Not specified

Radiotherapy:

• See Disease Characteristics

Surgery:

• Not specified

Other:

• At least 6 months since prior coronary angioplasty
• No other concurrent investigational drugs
• No concurrent non-steroidal anti-inflammatory drugs, salicylate, sulfonamide, trimethoprim, allopurinol, aminoglycoside, amoxicillin, or probenecid during high-dose methotrexate administration

Belgium
      Algemeen Ziekenhuis Sint Lucas, Gent,  B-9000,  Belgium; Recruiting
      Institut Jules Bordet, Brussels,  1000,  Belgium; Recruiting
      Universitair Ziekenhuis Antwerpen, Edegem,  B-2650,  Belgium; Recruiting
      Ziekenhuis Network Antwerpen Middelheim, Antwerp,  2020,  Belgium; Recruiting
Croatia
      University Hospital Rebro, Zagreb,  10000,  Croatia; Recruiting
Denmark
      Rigshospitalet, Copenhagen,  2100,  Denmark; Recruiting
Germany
      Carl - Thiem - Klinkum Cottbus, Cottbus,  D-03048,  Germany; Recruiting
      Charite - Campus Charite Mitte, Berlin,  D-10117,  Germany; Recruiting
      Charite - Campus Virchow Klinikum, Berlin,  D-13353,  Germany; Recruiting
      Charite - Universitaetsmedizin Berlin - Campus Benjamin Franklin, Berlin,  D-12200,  Germany; Recruiting
      Clinic for Bone Marrow Transplantation and Hematology and Oncology, Idar-Oberstein,  D-55743,  Germany; Recruiting
      Diakonissen-Krankenhaus Stuttgart, Stuttgart,  D-70176,  Germany; Recruiting
      Dr. Horst-Schmidt-Kliniken, Wiesbaden,  D-65199,  Germany; Recruiting
      Evangelische Krankenhaus Hamm, Hamm,  DOH-59063,  Germany; Recruiting
      Evangelisches Krankenhaus Essen Werden, ESSEN,  D-45239,  Germany; Recruiting
      Klinik Fuer Innere Medizin, Hematology/Oncology, Ernst Moritz Armdt Universitaet, Greifswald,  D-17487,  Germany; Recruiting
      Klinikum der Friedrich-Schiller Universitaet Jena, Jena,  D-07740,  Germany; Recruiting
      Klinikum Grosshadern der Ludwig-Maximilians Universitaet Muenchen, Munich,  D-81377,  Germany; Recruiting
      Klinikum Oldenburg, Oldenburg,  D-26133,  Germany; Recruiting
      Klinikum Rechts Der Isar - Technische Universitaet Muenchen, Munich,  D-81675,  Germany; Recruiting
      Krankenhaus Maria Hilf GmbH, Moenchengladbach,  DOH-41063,  Germany; Recruiting
      Krankenhaus Muenchen Schwabing, Munich,  80804,  Germany; Recruiting
      Krankenhaus Siloah - Medizinische Klinik II, Hannover,  D-30449,  Germany; Recruiting
      Martin Luther Universitaet, Halle,  D-06120,  Germany; Recruiting
      Medizinische Hochschule Hannover, Hannover,  D-30625,  Germany; Recruiting
      Medizinische Poliklinik, Bonn,  D-53111,  Germany; Recruiting
      Medizinische Universitaetsklinik I, Cologne,  D-50924,  Germany; Recruiting
      Medizinische Universitaetsklinik und Poliklinik, Heidelberg,  69115,  Germany; Recruiting
      Saint Georg-Hospital, Hamburg,  D-20099,  Germany; Recruiting
      St. Bernward Krankenhaus 1267, Hildeshem,  D-31134,  Germany; Recruiting
      Staedt Klinikum Karlsruhe GGMBH, Karlsruhe,  76133,  Germany; Recruiting
      Staedtisches Klinikum Dessau, Dessau,  D-06822,  Germany; Recruiting
      Universitaetsklinikum Essen, ESSEN,  D-45122,  Germany; Recruiting
      Universitaetsklinikum Schleswig-Holstein - Campus Luebeck, Luebeck,  D-23538,  Germany; Recruiting
      Universitaets-Krankenhaus Eppendorf, Hamburg,  D-20246,  Germany; Recruiting
      Universitatsklinik - Saarland, Homburg,  D-66421,  Germany; Recruiting
      Urologische Klinik, Giessen,  D-35392,  Germany; Recruiting
Netherlands
      Academisch Medisch Centrum, Amsterdam,  1105 AZ,  Netherlands; Recruiting
      Academisch Ziekenhuis Maastricht, Maastricht,  6202 AZ,  Netherlands; Recruiting
      Leiden University Medical Center, Leiden,  2300 RC,  Netherlands; Recruiting
      Maxima Medisch Centrum - locatie Veldhoven, VELDHOVEN,  5500 MB,  Netherlands; Recruiting
      Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital, Amsterdam,  1066 CX,  Netherlands; Recruiting
      Onze Lieve Vrouwe Gasthuis, Amsterdam,  1091 HA,  Netherlands; Recruiting
      University Medical Center Groningen, Groningen,  9700 RB,  Netherlands; Recruiting
      University Medical Center Nijmegen, Nijmegen,  NL-6500 HB,  Netherlands; Recruiting
Poland
      Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Warsaw,  02-781,  Poland; Recruiting
Portugal
      Hospitais da Universidade de Coimbra (HUC), Coimbra,  P-3001-301,  Portugal; Recruiting
Switzerland
      UniversitaetsSpital, Zurich,  CH-8091,  Switzerland; Recruiting

Study chairs or principal investigators

Andreas Engert, MD,  Medizinische Universitaetsklinik I   
J. W. Baars, MD, PhD,  Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital   
Norbert Schmitz, MD, PhD,  Saint Georg-Hospital   

Study ID Numbers:  CDR0000068981; GHSG-HD-R2; EBMT-GHSG-HD-R2; EORTC-20011; NCT00025636
Record last reviewed:  December 2004
Last Updated:  April 4, 2005
Record first received:  October 11, 2001
ClinicalTrials.gov Identifier:  NCT00025636
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08