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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00012051
Recruitment Status : Completed
First Posted : January 27, 2003
Last Update Posted : August 12, 2013
Sponsor:
Information provided by:
National Cancer Institute (NCI)

Tracking Information
First Submitted Date  ICMJE March 3, 2001
First Posted Date  ICMJE January 27, 2003
Last Update Posted Date August 12, 2013
Study Start Date  ICMJE September 2000
Primary Completion Date Not Provided
Current Primary Outcome Measures  ICMJE
 (submitted: December 11, 2006)
Overall survival
Original Primary Outcome Measures  ICMJE Not Provided
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: December 11, 2006)
  • Response rate
  • Event-free survival
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Chemotherapy and Peripheral Stem Cell Transplant With or Without Monoclonal Antibody Therapy in Treating Patients With Non-Hodgkin's Lymphoma
Official Title  ICMJE 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)
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.

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  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Primary Purpose: Treatment
Condition  ICMJE Lymphoma
Intervention  ICMJE
  • 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
Study Arms  ICMJE Not Provided
Publications * Vellenga E, van Putten WL, van 't Veer MB, Zijlstra JM, Fibbe WE, van Oers MH, Verdonck LF, Wijermans PW, van Imhoff GW, Lugtenburg PJ, Huijgens PC. Rituximab improves the treatment results of DHAP-VIM-DHAP and ASCT in relapsed/progressive aggressive CD20+ NHL: a prospective randomized HOVON trial. Blood. 2008 Jan 15;111(2):537-43. Epub 2007 Oct 30.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Estimated Enrollment  ICMJE
 (submitted: November 8, 2006)
340
Original Enrollment  ICMJE Not Provided
Actual Study Completion Date  ICMJE October 2007
Primary Completion Date Not Provided
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 65 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Belgium,   Netherlands
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00012051
Other Study ID Numbers  ICMJE CKTO-2000-06
CDR0000068476 ( Registry Identifier: PDQ (Physician Data Query) )
HOVON-44
HOVON-44/CKVO-2000-06
EU-20042
ISRCTN95614846
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Not Provided
Study Sponsor  ICMJE Commissie Voor Klinisch Toegepast Onderzoek
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Chair: Edo Vellenga, MD University Medical Center Groningen
PRS Account National Cancer Institute (NCI)
Verification Date March 2007

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP