Combination Chemotherapy Plus Peripheral Stem Cell Transplantation With or Without Rituximab in Treating Patients With Relapsed 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. Identifier: NCT00005589
Recruitment Status : Completed
First Posted : January 27, 2003
Last Update Posted : September 17, 2013
Lymphoma Trials Office
Information provided by:
National Cancer Institute (NCI)

May 2, 2000
January 27, 2003
September 17, 2013
October 1999
Not Provided
Time to disease progression
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Complete list of historical versions of study NCT00005589 on Archive Site
  • Response rate and survival
  • Molecular remission rates
  • Safety
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Combination Chemotherapy Plus Peripheral Stem Cell Transplantation With or Without Rituximab in Treating Patients With Relapsed Non-Hodgkin's Lymphoma
Randomized Study of Rituximab (Mabthera) in Patients With Relapsed Follicular Lymphoma Prior to High-Dose Therapy as In Vivo Purging and to Maintain Remission Following High-Dose Therapy

RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Peripheral stem cell transplantation may allow the doctor to give higher doses of chemotherapy drugs and kill more cancer cells. Monoclonal antibodies such as rituximab can locate cancer cells and either kill them or deliver cancer-killing substances to them without harming normal cells. It is not yet known if combination chemotherapy plus peripheral stem cell transplantation is more effective with or without rituximab for non-Hodgkin's lymphoma.

PURPOSE: This randomized phase III trial is studying giving combination chemotherapy and peripheral stem cell transplantation together with rituximab to see how well it works compared to combination chemotherapy and peripheral stem cell transplantation alone in treating patients with relapsed non-Hodgkin's lymphoma.


  • Determine the effects of in vivo rituximab purging and maintenance on progression-free survival in patients with relapsed or resistant follicular non-Hodgkin's lymphoma undergoing high-dose chemotherapy.
  • Determine the effects of this regimen on response rate and overall survival in this patient population.
  • Determine the effects of in vivo purging with rituximab on molecular remission rates in the hematopoietic product and the patients.
  • Determine the safety of rituximab in the transplant setting.

OUTLINE: This is a randomized, open-label, multicenter study. Patients are stratified according to type of remission (complete vs good partial) and which remission (second vs third). Patients are randomized to one of four treatment arms.

All patients receive induction chemotherapy comprising cyclophosphamide IV over 3-4 hours on day 0 or a standard induction chemotherapy regimen. Filgrastim (G-CSF) is administered subcutaneously daily beginning on day 1.

Patients are then randomized to receive either in vivo rituximab purging or no purging following restaging after completion of induction. For those patients receiving purging (arms I and II), rituximab is administered IV once weekly for 4 weeks.

Peripheral blood stem cells (PBSC) are collected between days 8 and 12 post induction chemotherapy. Within 4 weeks of PBSC collection, patients receive carmustine IV over 2 hours on day -6, etoposide IV over 2 hours on days -5 to -2, cytarabine IV over 5 minutes twice daily on days -5 to -2, and melphalan IV over 10-15 minutes on day -1. (Alternatively, high dose cyclophosphamide and total body irradiation beginning 2-4 weeks after cyclophosphamide or standard induction chemotherapy priming is also allowed.) PBSC are reinfused on day 0.

Patients are further randomized to receive either rituximab maintenance or observation only. For those patients receiving maintenance (arms I and III), rituximab is administered IV once every 2 months for 4 doses beginning 30 days after PBSC reinfusion.

Patients are followed at 30 days, 3, 6, 9, and 12 months after PBSC transplant, every 6 months for 2 years, and then annually thereafter.

PROJECTED ACCRUAL: A total of 460 patients (115 per treatment arm) will be accrued for this study within 5 years.

Phase 3
Allocation: Randomized
Masking: None (Open Label)
Primary Purpose: Treatment
  • Biological: filgrastim
  • Biological: rituximab
  • Drug: carmustine
  • Drug: cyclophosphamide
  • Drug: cytarabine
  • Drug: etoposide
  • Drug: melphalan
  • Procedure: bone marrow ablation with stem cell support
  • Procedure: peripheral blood stem cell transplantation
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Pettengell R, Schmitz N, Gisselbrecht C, Smith G, Patton WN, Metzner B, Caballero D, Tilly H, Walewski JA, Bence-Bruckler I, To B, Geisler CH, Schots R, Kimby E, Taverna CJ, Kozák T, Dreger P, Uddin R, Ruiz de Elvira C, Goldstone AH. Rituximab purging and/or maintenance in patients undergoing autologous transplantation for relapsed follicular lymphoma: a prospective randomized trial from the lymphoma working party of the European group for blood and marrow transplantation. J Clin Oncol. 2013 May 1;31(13):1624-30. doi: 10.1200/JCO.2012.47.1862. Epub 2013 Apr 1.

*   Includes publications given by the data provider as well as publications identified by Identifier (NCT Number) in Medline.
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April 2013
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  • Relapsed or resistant follicular non-Hodgkin's lymphoma (NHL)

    • No evidence of transformation to high grade or diffuse large B-cell NHL
  • CD20 positive with no evidence of transformation
  • Achievement of complete remission (CR) or very good partial remission (VGPR) following reinduction chemotherapy with any standard regimen

    • Includes patients who fail to respond to first-line chemotherapy but who achieve CR or VGPR after proceeding directly to second-line chemotherapy
  • Platelet count greater than 100,000/mm^3 after induction chemotherapy and before randomization
  • No CNS involvement



  • 18 and over

Performance status:

  • WHO 0-1

Life expectancy:

  • Not specified


  • See Disease Characteristics


  • Bilirubin normal
  • ALT no greater than 2 times upper limit of normal (ULN)
  • Alkaline phosphatase no greater than 2 times ULN
  • Hepatitis B negative
  • Hepatitis C negative


  • Creatinine no greater than 2 times ULN
  • BUN no greater than 2 times ULN


  • No inadequate cardiac function


  • No inadequate pulmonary function


  • Not pregnant or nursing
  • HIV negative
  • No other uncontrolled serious medical conditions
  • No other malignancy within the past 5 years except nonmelanoma skin tumors or carcinoma in situ of the cervix


Biologic therapy:

  • More than 12 months since prior CD20 therapy, including rituximab
  • No prior peripheral blood stem cell transplantation


  • See Disease Characteristics
  • No more than 3 prior chemotherapy regimens for NHL

Endocrine therapy:

  • Not specified


  • No prior radiotherapy to greater than 30% of bone marrow


  • Not specified
Sexes Eligible for Study: All
18 Years and older   (Adult, Older Adult)
Contact information is only displayed when the study is recruiting subjects
Australia,   Austria,   Belgium,   Canada,   Czech Republic,   Denmark,   France,   Germany,   Israel,   New Zealand,   Poland,   Portugal,   Spain,   Sweden,   Switzerland,   Turkey,   United Kingdom
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EBMT Solid Tumors Working Party
Lymphoma Trials Office
Study Chair: Ruth Pettengell, MD St George's, University of London
Study Chair: David C. Linch Middlesex Hospital
National Cancer Institute (NCI)
March 2007

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