Combination Chemotherapy and Peripheral Stem Cell Transplant in Treating Patients With Relapsed Hodgkin's Lymphoma

NCT ID: NCT00025636

Last Updated: 2013-09-17

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE3
• Total Enrollment: 220 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2001-07-31

Brief Summary

RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Peripheral stem cell transplant 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 transplant is more effective in treating relapsed Hodgkin's lymphoma.

PURPOSE: This randomized phase III trial is comparing different regimens of combination chemotherapy followed by peripheral stem cell transplant to see how well they work in treating patients with relapsed Hodgkin's lymphoma.

Detailed Description

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.

Conditions

Lymphoma

Keywords

recurrent adult Hodgkin lymphoma

Study Design

• Allocation Method: RANDOMIZED
• Primary Study Purpose: TREATMENT

Interventions

filgrastim

Intervention Type: BIOLOGICAL

carmustine

Intervention Type: DRUG

cisplatin

Intervention Type: DRUG

cyclophosphamide

Intervention Type: DRUG

cytarabine

Intervention Type: DRUG

dexamethasone

Intervention Type: DRUG

etoposide

Intervention Type: DRUG

melphalan

Intervention Type: DRUG

methotrexate

Intervention Type: DRUG

vincristine sulfate

Intervention Type: DRUG

bone marrow ablation with stem cell support

Intervention Type: PROCEDURE

peripheral blood stem cell transplantation

Intervention Type: PROCEDURE

Eligibility Criteria

Inclusion 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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 60 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

European Organisation for Research and Treatment of Cancer - EORTC

NETWORK

Sponsor Role: collaborator

EBMT Solid Tumors Working Party

OTHER

Sponsor Role: collaborator

German Hodgkin's Lymphoma Study Group

OTHER

Sponsor Role: lead

Principal Investigators

Andreas Engert, MD

Role:

Medizinische Universitaetsklinik I at the University of Cologne

J. W. Baars, MD, PhD

Role:

The Netherlands Cancer Institute

Norbert Schmitz, MD, PhD

Role:

Asklepios Klinik St. Georg

Locations

Ziekenhuis Netwerk Antwerpen Middelheim

Antwerp, , Belgium

Institut Jules Bordet

Brussels, , Belgium

Universitair Ziekenhuis Antwerpen

Edegem, , Belgium

Algemeen Ziekenhuis Sint Lucas

Ghent, , Belgium

University Hospital Rebro

Zagreb, , Croatia

Rigshospitalet - Copenhagen University Hospital

Copenhagen, , Denmark

Charite - Campus Charite Mitte

Berlin, , Germany

Charite - Universitaetsmedizin Berlin - Campus Benjamin Franklin

Berlin, , Germany

Charite - Campus Virchow Klinikum

Berlin, , Germany

Medizinische Poliklinik

Bonn, , Germany

Medizinische Universitaetsklinik I at the University of Cologne

Cologne, , Germany

Staedtisches Klinikum Dessau

Dessau, , Germany

Universitaetsklinikum Essen

Essen, , Germany

Evangelisches Krankenhaus Essen Werden

Essen, , Germany

Klinik Fuer Innere Medizin, Hematology/Oncology, Ernst Moritz Armdt Universitaet

Greifswald, , Germany

Martin Luther Universitaet

Halle, , Germany

Asklepios Klinik St. Georg

Hamburg, , Germany

Universitaetsklinikum Hamburg-Eppendorf

Hamburg, , Germany

Evangelische Krankenhaus Hamm

Hamm, , Germany

Krankenhaus Siloah - Medizinische Klinik II

Hanover, , Germany

Medizinische Hochschule Hannover

Hanover, , Germany

Medizinische Universitaetsklinik und Poliklinik

Heidelberg, , Germany

St. Bernward Krankenhaus

Hildeshem, , Germany

Universitaetsklinikum des Saarlandes

Homburg, , Germany

Clinic for Bone Marrow Transplantation and Hematology and Oncology

Idar-Oberstein, , Germany

Klinikum der Friedrich-Schiller Universitaet Jena

Jena, , Germany

Staedtisches Klinikum Karlsruhe gGmbH

Karlsruhe, , Germany

Universitaetsklinikum Schleswig-Holstein - Campus Luebeck

Lübeck, , Germany

Krankenhaus Muenchen Schwabing

Munich, , Germany

Klinikum der Universitaet Muenchen - Grosshadern Campus

Munich, , Germany

Klinikum Rechts Der Isar - Technische Universitaet Muenchen

Munich, , Germany

Diakonie Klinikum Stuttgart

Stuttgart, , Germany

Dr. Horst-Schmidt-Kliniken

Wiesbaden, , Germany

Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital

Amsterdam, , Netherlands

Onze Lieve Vrouwe Gasthuis

Amsterdam, , Netherlands

Academisch Medisch Centrum at University of Amsterdam

Amsterdam, , Netherlands

University Medical Center Groningen

Groningen, , Netherlands

Leiden University Medical Center

Leiden, , Netherlands

Academisch Ziekenhuis Maastricht

Maastricht, , Netherlands

Universitair Medisch Centrum St. Radboud - Nijmegen

Nijmegen, , Netherlands

Maxima Medisch Centrum - Veldhoven

Veldhoven, , Netherlands

Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology

Warsaw, , Poland

Hospitais da Universidade de Coimbra (HUC)

Coimbra, , Portugal

UniversitaetsSpital Zuerich

Zurich, , Switzerland

Countries

Belgium; Croatia; Denmark; Germany; Netherlands; Poland; Portugal; Switzerland

References

Brockelmann PJ, Muller H, Casasnovas O, Hutchings M, von Tresckow B, Jurgens M, McCall SJ, Morschhauser F, Fuchs M, Borchmann P, Moskowitz CH, Engert A. Risk factors and a prognostic score for survival after autologous stem-cell transplantation for relapsed or refractory Hodgkin lymphoma. Ann Oncol. 2017 Jun 1;28(6):1352-1358. doi: 10.1093/annonc/mdx072.

Reference Type: DERIVED

PMID: 28327958 (View on PubMed)

Other Identifiers

GHSG-HD-R2

Identifier Type: -

Identifier Source: secondary_id

EBMT-GHSG-HD-R2

Identifier Type: -

Identifier Source: secondary_id

EORTC-20011

Identifier Type: -

Identifier Source: secondary_id

CDR0000068981

Identifier Type: -

Identifier Source: org_study_id