Combination Chemotherapy Plus Peripheral Stem Cell Transplantation With or Without Rituximab in Treating Patients With Relapsed Non-Hodgkin's Lymphoma

This study has been completed.
Sponsor:
Collaborator:
Lymphoma Trials Office
Information provided by:
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00005589
First received: May 2, 2000
Last updated: September 16, 2013
Last verified: March 2007

May 2, 2000
September 16, 2013
October 1999
Not Provided
Time to disease progression [ Designated as safety issue: No ]
Not Provided
Complete list of historical versions of study NCT00005589 on ClinicalTrials.gov Archive Site
  • Response rate and survival [ Designated as safety issue: No ]
  • Molecular remission rates [ Designated as safety issue: No ]
  • Safety [ Designated as safety issue: Yes ]
Not Provided
Not Provided
Not Provided
 
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.

OBJECTIVES:

  • 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.

Interventional
Phase 3
Allocation: Randomized
Masking: Open Label
Primary Purpose: Treatment
Lymphoma
  • 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
Not Provided
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 ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
460
April 2013
Not Provided

DISEASE CHARACTERISTICS:

  • 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

PATIENT CHARACTERISTICS:

Age:

  • 18 and over

Performance status:

  • WHO 0-1

Life expectancy:

  • Not specified

Hematopoietic:

  • See Disease Characteristics

Hepatic:

  • 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

Renal:

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

Cardiovascular:

  • No inadequate cardiac function

Pulmonary:

  • No inadequate pulmonary function

Other:

  • 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

PRIOR CONCURRENT THERAPY:

Biologic therapy:

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

Chemotherapy:

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

Endocrine therapy:

  • Not specified

Radiotherapy:

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

Surgery:

  • Not specified
Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
Denmark,   United Kingdom,   Belgium,   Austria,   Germany,   New Zealand,   France,   Spain,   Israel,   Australia,   Turkey,   Portugal,   Poland,   Switzerland,   Sweden,   Canada,   Czech Republic
 
NCT00005589
CDR0000067665, EBMT-EBMTLYM1, BNLI-EBMT-EBMTLYM1, EU-99050
Not Provided
Not Provided
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