Chemotherapy and Peripheral Stem Cell Transplant With or Without Monoclonal Antibody Therapy in Treating Patients With Non-Hodgkin's Lymphoma

Sponsor

Commissie Voor Klinisch Toegepast Onderzoek (Other)

Overall Status

Completed

CT.gov ID

NCT00012051

Collaborator

(none)

340

Enrollment

Locations

Duration (Months)

Patients Per Site

0.2

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

RATIONALE: Drugs used in chemotherapy work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Peripheral stem cell transplant may be able to replace immune cells that were destroyed by the chemotherapy. Monoclonal antibodies, such as rituximab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. It is not yet known if giving more than one drug (combination chemotherapy) plus peripheral stem cell transplant is more effective with or without monoclonal antibody therapy in treating non-Hodgkin's lymphoma.

PURPOSE: This randomized phase III trial is studying how well chemotherapy plus peripheral stem cell transplant with or without monoclonal antibody therapy works in treating patients with relapsed non-Hodgkin's lymphoma.

Condition or Disease	Intervention/Treatment	Phase
Lymphoma	Biological: filgrastim Biological: rituximab Drug: carmustine Drug: cisplatin Drug: cytarabine Drug: dexamethasone Drug: etoposide Drug: ifosfamide Drug: melphalan Drug: methotrexate Procedure: bone marrow ablation with stem cell support Procedure: peripheral blood stem cell transplantation Radiation: radiation therapy	Phase 3

Detailed Description

OBJECTIVES:

Compare the partial and complete response rates in patients with relapsed, CD20 positive, aggressive B-cell non-Hodgkin's lymphoma treated with dexamethasone, cisplatin, and cytarabine in combination with etoposide, ifosfamide, and methotrexate with or without rituximab followed by carmustine, etoposide, cytarabine, melphalan, and autologous peripheral blood stem cell transplantation (APBSCT).
Compare the effect of APBSCT with or without rituximab on the overall and event-free survival of these patients.

OUTLINE: This is a randomized, multicenter study. Patients are stratified according to participating center. Patients are randomized to one of two treatment arms.

Arm I: Patients receive DHAP induction chemotherapy comprising dexamethasone orally or IV on days 1-4, cisplatin IV continuously over 24 hours on day 1, and cytarabine IV over 3 hours every 12 hours on day 2. Beginning 3-4 weeks after DHAP, patients receive VIM induction chemotherapy comprising etoposide IV over 2 hours on days 1, 3, and 5; ifosfamide IV over 1 hour on days 1-5; and methotrexate IV on days 1 and 5. Beginning 3-4 weeks after VIM, patients with partial or complete response after DHAP and VIM receive a second course of DHAP (patients with progressive or unresponsive disease after DHAP but responsive disease after VIM receive a second course of VIM) followed by filgrastim (G-CSF) subcutaneously beginning on day 10 and continuing until a target number of cells are collected.
Arm II: Patients receive induction chemotherapy and G-CSF as in arm I. At 1 day after the last dose of each chemotherapy course, patients also receive rituximab IV once for a maximum of 3 courses.

At 4-5 weeks after the completion of the last induction chemotherapy course, responsive patients in both arms receive BEAM conditioning chemotherapy comprising carmustine IV over 60 minutes on day -6, etoposide IV over 60 minutes and cytarabine IV over 30 minutes on days -5 to -2, and melphalan IV over 15 minutes on day -1. Patients undergo autologous peripheral blood stem cell transplantation on day 0. After transplantation, patients in partial remission may undergo radiotherapy to nodal sites with residual tumor mass.

Patients are followed every 6 months for 3 years and then annually thereafter.

PROJECTED ACCRUAL: A total of 296-340 patients (148-170 per treatment arm) will be accrued for this study within 4-5 years.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

340 participants

Allocation:

Randomized

Primary Purpose:

Treatment

Official Title:

A Randomised Phase III Study On The Effect Of The Chimeric Anti-CD20 Monoclonal Antibody (Mabthera) During Sequential Chemotherapy Followed By Autologous Stem Cell Transplantation In Patients With Relapse B-Cell Non-Hodgkin Lymphoma(HOVON 44 STUDY)

Study Start Date :

Sep 1, 2000

Actual Study Completion Date :

Oct 1, 2007

Outcome Measures

Primary Outcome Measures

Overall survival []

Secondary Outcome Measures

Response rate []
Event-free survival []

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 65 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

DISEASE CHARACTERISTICS:

Histologically confirmed relapsed B-cell non-Hodgkin's lymphoma (NHL)
Diffuse large cell B-cell lymphoma
Grade III follicular center-cell lymphoma
Primary mediastinal B-cell lymphoma
CD20 positive
First relapse after doxorubicin containing regimen
Documented remission of at least 3 months after first-line chemotherapy
No Epstein-Barr virus post-transplantation lymphoproliferative disorder
No CNS involvement

PATIENT CHARACTERISTICS:

Age:

18 to 65

Performance status:

WHO 0-1

Life expectancy:

Not specified

Hematopoietic:

Not specified

Hepatic:

No hepatic dysfunction
Bilirubin less than 2.5 times upper limit of normal (ULN)
Transaminases less than 2.5 times ULN

Renal:

No renal dysfunction
Creatinine less than 2.0 mg/dL OR
Creatinine clearance greater than 40 mL/min

Cardiovascular:

No severe cardiac dysfunction
No New York Heart association class II-IV heart disease

Pulmonary:

No severe pulmonary dysfunction
Vital capacity or diffusion capacity at least 70% predicted unless related to NHL involvement

Other:

No active uncontrolled infection
HIV negative
No intolerance to exogenous protein administration

PRIOR CONCURRENT THERAPY:

Biologic therapy:

At least 1 month since prior immunotherapy

Chemotherapy:

See Disease Characteristics
At least 1 month since prior chemotherapy

Endocrine therapy:

Not specified

Radiotherapy:

At least 1 month since prior radiotherapy

Surgery:

Not specified

Contacts and Locations

Locations

	Site	City	Country	Postal Code
1	U.Z. Gasthuisberg	Leuven	Belgium	B-3000
2	HagaZiekenhuis - Locatie Leyenburg	's-Gravenhage	Netherlands	2545 CH
3	Jeroen Bosch Ziekenhuis	's-Hertogenbosch	Netherlands	5211 NL
4	Meander Medisch Centrum	Amersfoort	Netherlands	3816 CP
5	Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital	Amsterdam	Netherlands	1066 BE
6	Vrije Universiteit Medisch Centrum	Amsterdam	Netherlands	1081HV
7	Academisch Medisch Centrum at University of Amsterdam	Amsterdam	Netherlands	1105 AZ
8	Medisch Spectrum Twente	Enschede	Netherlands	7500 KA
9	University Medical Center Groningen	Groningen	Netherlands	9713 EZ
10	Medisch Centrum Leeuwarden - Zuid	Leeuwarden	Netherlands	8934 AD
11	Leiden University Medical Center	Leiden	Netherlands	2300 CA
12	Academisch Ziekenhuis Maastricht	Maastricht	Netherlands	6202 AZ
13	Sint Antonius Ziekenhuis	Nieuwegein	Netherlands	3435 CM
14	Universitair Medisch Centrum St. Radboud - Nijmegen	Nijmegen	Netherlands	NL-6500 HB
15	Daniel Den Hoed Cancer Center at Erasmus Medical Center	Rotterdam	Netherlands	3008 AE
16	University Medical Center Utrecht	Utrecht	Netherlands	3584 CX
17	Isala Klinieken - locatie Sophia	Zwolle	Netherlands	8000 GK