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

August 9, 2013 updated by: Commissie Voor Klinisch Toegepast Onderzoek

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)

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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 Type

Interventional

Enrollment (Anticipated)

340

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

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

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 65 years (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: RANDOMIZED

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Overall survival

Secondary Outcome Measures

Outcome Measure
Response rate
Event-free survival

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Commissie Voor Klinisch Toegepast Onderzoek

Investigators

  • Study Chair: Edo Vellenga, MD, University Medical Center Groningen

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

September 1, 2000

Study Completion (Actual)

October 1, 2007

Study Registration Dates

First Submitted

March 3, 2001

First Submitted That Met QC Criteria

January 26, 2003

First Posted (Estimate)

January 27, 2003

Study Record Updates

Last Update Posted (Estimate)

August 12, 2013

Last Update Submitted That Met QC Criteria

August 9, 2013

Last Verified

March 1, 2007

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CKTO-2000-06
  • CDR0000068476 (Registry Identifier: PDQ (Physician Data Query))
  • HOVON-44
  • HOVON-44/CKVO-2000-06
  • EU-20042
  • ISRCTN95614846

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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