Clinical trial NCT00025636: Combination Chemotherapy and Peripheral Stem Cell Transplant in Treating Patients With Relapsed Hodgkin's Lymphoma
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
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE3
Conditions: Lymphoma
Keywords: recurrent adult Hodgkin lymphoma
Lead sponsor: National Cancer Institute (NCI)
Sponsor class: NIH
Collaborators: name: European Organisation for Research and Treatment of Cancer - EORTC
name: EBMT Solid Tumors Working Party
First posted: 2003-01-27
Enrollment: 220
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Primary purpose: TREATMENT

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.

Eligibility 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

Primary outcomes:
measure: Efficacy at 3 months
measure: Toxicity at 3 months
Secondary outcomes:
measure: Complete remission at 3 months
measure: Relapse-free survival at 3 months
measure: Overall survival at 3 months
Other outcomes:
Locations:
city: Antwerp
country: Belgium
facility: Ziekenhuis Netwerk Antwerpen Middelheim
city: Brussels
country: Belgium
facility: Institut Jules Bordet
city: Edegem
country: Belgium
facility: Universitair Ziekenhuis Antwerpen
city: Ghent
country: Belgium
facility: Algemeen Ziekenhuis Sint Lucas
city: Zagreb
country: Croatia
facility: University Hospital Rebro
city: Copenhagen
country: Denmark
facility: Rigshospitalet - Copenhagen University Hospital
city: Berlin
country: Germany
facility: Charite - Campus Charite Mitte
city: Berlin
country: Germany
facility: Charite - Universitaetsmedizin Berlin - Campus Benjamin Franklin
city: Berlin
country: Germany
facility: Charite - Campus Virchow Klinikum
city: Bonn
country: Germany
facility: Medizinische Poliklinik
city: Cologne
country: Germany
facility: Medizinische Universitaetsklinik I at the University of Cologne
city: Dessau
country: Germany
facility: Staedtisches Klinikum Dessau
city: Essen
country: Germany
facility: Universitaetsklinikum Essen
city: Essen
country: Germany
facility: Evangelisches Krankenhaus Essen Werden
city: Greifswald
country: Germany
facility: Klinik Fuer Innere Medizin, Hematology/Oncology, Ernst Moritz Armdt Universitaet
city: Halle
country: Germany
facility: Martin Luther Universitaet
city: Hamburg
country: Germany
facility: Asklepios Klinik St. Georg
city: Hamburg
country: Germany
facility: Universitaetsklinikum Hamburg-Eppendorf
city: Hamm
country: Germany
facility: Evangelische Krankenhaus Hamm
city: Hannover
country: Germany
facility: Krankenhaus Siloah - Medizinische Klinik II
city: Hannover
country: Germany
facility: Medizinische Hochschule Hannover
city: Heidelberg
country: Germany
facility: Medizinische Universitaetsklinik und Poliklinik
city: Hildeshem
country: Germany
facility: St. Bernward Krankenhaus
city: Homburg
country: Germany
facility: Universitaetsklinikum des Saarlandes
city: Idar-Oberstein
country: Germany
facility: Clinic for Bone Marrow Transplantation and Hematology and Oncology
city: Jena
country: Germany
facility: Klinikum der Friedrich-Schiller Universitaet Jena
city: Karlsruhe
country: Germany
facility: Staedtisches Klinikum Karlsruhe gGmbH
city: Luebeck
country: Germany
facility: Universitaetsklinikum Schleswig-Holstein - Campus Luebeck
city: Munich
country: Germany
facility: Krankenhaus Muenchen Schwabing
city: Munich
country: Germany
facility: Klinikum der Universitaet Muenchen - Grosshadern Campus
city: Munich
country: Germany
facility: Klinikum Rechts Der Isar - Technische Universitaet Muenchen
city: Stuttgart
country: Germany
facility: Diakonie Klinikum Stuttgart
city: Wiesbaden
country: Germany
facility: Dr. Horst-Schmidt-Kliniken
city: Amsterdam
country: Netherlands
facility: Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital
city: Amsterdam
country: Netherlands
facility: Onze Lieve Vrouwe Gasthuis
city: Amsterdam
country: Netherlands
facility: Academisch Medisch Centrum at University of Amsterdam
city: Groningen
country: Netherlands
facility: University Medical Center Groningen
city: Leiden
country: Netherlands
facility: Leiden University Medical Center
city: Maastricht
country: Netherlands
facility: Academisch Ziekenhuis Maastricht
city: Nijmegen
country: Netherlands
facility: Universitair Medisch Centrum St. Radboud - Nijmegen
city: Veldhoven
country: Netherlands
facility: Maxima Medisch Centrum - Veldhoven
city: Warsaw
country: Poland
facility: Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology
city: Coimbra
country: Portugal
facility: Hospitais da Universidade de Coimbra (HUC)
city: Zurich
country: Switzerland
facility: UniversitaetsSpital Zuerich
Study officials:
affiliation: Medizinische Universitaetsklinik I at the University of Cologne
name: Andreas Engert, MD
affiliation: The Netherlands Cancer Institute
name: J. W. Baars, MD, PhD
affiliation: Asklepios Klinik St. Georg
name: Norbert Schmitz, MD, PhD
References:
citation: 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.