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

Lymphoma Clinical Trial

Official title:

A Randomized Trial Of BEAM Plus PBSCT Versus Single Agent High-Dose Therapy Followed By BEAM Plus PBSCT In Patients With Relapsed Hodgkin's Disease

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT00025636
• Other study ID #: CDR0000068981
• Secondary ID: GHSG-HD-R2EBMT-G
• Status: Active, not recruiting
• Phase: Phase 3
• First received: October 11, 2001
• Last updated: September 16, 2013
• Start date: July 2001

Study information

• Verified date: June 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 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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 220
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 60 Years

Eligibility

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

Study Design

Allocation: Randomized, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Lymphoma

Intervention

Biological:
• filgrastim

Drug:
• carmustine

• cisplatin

• cyclophosphamide

• cytarabine

• dexamethasone

• etoposide

• melphalan

• methotrexate

• vincristine sulfate

Procedure:
• bone marrow ablation with stem cell support

• peripheral blood stem cell transplantation

Locations

Country	Name	City	State
Belgium	Ziekenhuis Netwerk Antwerpen Middelheim	Antwerp
Belgium	Institut Jules Bordet	Brussels
Belgium	Universitair Ziekenhuis Antwerpen	Edegem
Belgium	Algemeen Ziekenhuis Sint Lucas	Ghent
Croatia	University Hospital Rebro	Zagreb
Denmark	Rigshospitalet - Copenhagen University Hospital	Copenhagen
Germany	Charite - Campus Charite Mitte	Berlin
Germany	Charite - Campus Virchow Klinikum	Berlin
Germany	Charite - Universitaetsmedizin Berlin - Campus Benjamin Franklin	Berlin
Germany	Medizinische Poliklinik	Bonn
Germany	Medizinische Universitaetsklinik I at the University of Cologne	Cologne
Germany	Staedtisches Klinikum Dessau	Dessau
Germany	Evangelisches Krankenhaus Essen Werden	Essen
Germany	Universitaetsklinikum Essen	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	Hannover
Germany	Medizinische Hochschule Hannover	Hannover
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	Luebeck
Germany	Klinikum der Universitaet Muenchen - Grosshadern Campus	Munich
Germany	Klinikum Rechts Der Isar - Technische Universitaet Muenchen	Munich
Germany	Krankenhaus Muenchen Schwabing	Munich
Germany	Diakonie Klinikum Stuttgart	Stuttgart
Germany	Dr. Horst-Schmidt-Kliniken	Wiesbaden
Netherlands	Academisch Medisch Centrum at University of Amsterdam	Amsterdam
Netherlands	Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital	Amsterdam
Netherlands	Onze Lieve Vrouwe Gasthuis	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
Poland	Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology	Warsaw
Portugal	Hospitais da Universidade de Coimbra (HUC)	Coimbra
Switzerland	UniversitaetsSpital Zuerich	Zurich

Sponsors (3)

Lead Sponsor	Collaborator
German Hodgkin's Lymphoma Study Group	EBMT Solid Tumors Working Party, European Organisation for Research and Treatment of Cancer - EORTC

Countries where clinical trial is conducted

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

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Efficacy at 3 months			No
Primary	Toxicity at 3 months			Yes
Secondary	Complete remission at 3 months			No
Secondary	Relapse-free survival at 3 months			No
Secondary	Overall survival at 3 months			No