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

This study has been completed.
Sponsor:
Information provided by:
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00012051
First received: March 3, 2001
Last updated: August 9, 2013
Last verified: March 2007
  Purpose

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 Intervention 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

Study Type: Interventional
Study Design: 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)

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Overall survival [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Response rate [ Designated as safety issue: No ]
  • Event-free survival [ Designated as safety issue: No ]

Estimated Enrollment: 340
Study Start Date: September 2000
Study Completion Date: October 2007
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.

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
Please refer to this study by its ClinicalTrials.gov identifier: NCT00012051

Locations
Belgium
U.Z. Gasthuisberg
Leuven, Belgium, B-3000
Netherlands
HagaZiekenhuis - Locatie Leyenburg
's-Gravenhage, Netherlands, 2545 CH
Jeroen Bosch Ziekenhuis
's-Hertogenbosch, Netherlands, 5211 NL
Meander Medisch Centrum
Amersfoort, Netherlands, 3816 CP
Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital
Amsterdam, Netherlands, 1066 BE
Vrije Universiteit Medisch Centrum
Amsterdam, Netherlands, 1081HV
Academisch Medisch Centrum at University of Amsterdam
Amsterdam, Netherlands, 1105 AZ
Medisch Spectrum Twente
Enschede, Netherlands, 7500 KA
University Medical Center Groningen
Groningen, Netherlands, 9713 EZ
Medisch Centrum Leeuwarden - Zuid
Leeuwarden, Netherlands, 8934 AD
Leiden University Medical Center
Leiden, Netherlands, 2300 CA
Academisch Ziekenhuis Maastricht
Maastricht, Netherlands, 6202 AZ
Sint Antonius Ziekenhuis
Nieuwegein, Netherlands, 3435 CM
Universitair Medisch Centrum St. Radboud - Nijmegen
Nijmegen, Netherlands, NL-6500 HB
Daniel Den Hoed Cancer Center at Erasmus Medical Center
Rotterdam, Netherlands, 3008 AE
University Medical Center Utrecht
Utrecht, Netherlands, 3584 CX
Isala Klinieken - locatie Sophia
Zwolle, Netherlands, 8000 GK
Sponsors and Collaborators
Commissie Voor Klinisch Toegepast Onderzoek
Investigators
Study Chair: Edo Vellenga, MD University Medical Centre Groningen
  More Information

Additional Information:
Publications:
ClinicalTrials.gov Identifier: NCT00012051     History of Changes
Other Study ID Numbers: CKTO-2000-06, CDR0000068476, HOVON-44, HOVON-44/CKVO-2000-06, EU-20042, ISRCTN95614846
Study First Received: March 3, 2001
Last Updated: August 9, 2013
Health Authority: Unspecified

Keywords provided by National Cancer Institute (NCI):
recurrent grade 3 follicular lymphoma
recurrent adult diffuse large cell lymphoma

Additional relevant MeSH terms:
Lymphoma
Lymphoma, Non-Hodgkin
Lymphoma, B-Cell
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Antibodies, Monoclonal
Cytarabine
Melphalan
Methotrexate
Lenograstim
Rituximab
Carmustine
Ifosfamide
Isophosphamide mustard
Cisplatin
Dexamethasone
Etoposide
Dexamethasone acetate
Dexamethasone 21-phosphate
BB 1101
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on April 15, 2014