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Combination Chemotherapy With or Without Rituximab in Treating Patients With Relapsed Non-Hodgkin's Lymphoma

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ClinicalTrials.gov Identifier: NCT00004179
Recruitment Status : Completed
First Posted : January 27, 2003
Last Update Posted : July 27, 2017
Information provided by (Responsible Party):

Study Description
Brief Summary:

RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. 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 whether chemotherapy is more effective with or without rituximab for relapsed non-Hodgkin's lymphoma.

PURPOSE: This randomized phase III trial is studying combination chemotherapy and rituximab to see how well they work compared to combination chemotherapy alone in treating patients with relapsed non-Hodgkin's lymphoma.

Condition or disease Intervention/treatment Phase
Lymphoma Biological: rituximab Drug: CHOP regimen Drug: cyclophosphamide Drug: doxorubicin hydrochloride Drug: prednisone Drug: vincristine sulfate Phase 3

Detailed Description:


  • Compare the response rate and quality of remission in patients with relapsed follicular non-Hodgkin's lymphoma treated with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) with or without rituximab.
  • Compare the event-free survival and overall survival of patients treated with these regimens.
  • Determine the effect of rituximab as maintenance therapy on progression-free survival of these patients.

OUTLINE: This is a randomized, multicenter study.

  • Induction: Patients are randomized to one of two treatment arms. Patients are stratified according to participating center, prior treatment with purine analogues, age, number of prior induction treatments and best response obtained (complete vs partial remission vs no change/progressive disease), time since diagnosis (less than 2 years vs more than 2 years), and bulky disease (less than 10 cm vs greater than 10 cm).

    • Arm I (closed as of 12/20/04): Patients receive induction chemotherapy comprising cyclophosphamide IV, doxorubicin IV, and vincristine IV on day 1 and oral prednisone on days 1-5 (CHOP chemotherapy). Treatment repeats every 3 weeks for 6 courses in the absence of disease progression or unacceptable toxicity.
    • Arm II: Patients receive CHOP chemotherapy as in arm I. Rituximab IV is administered 1 hour after prednisone and before the IV drugs.
  • Maintenance: Patients who achieve partial or complete remission are then randomized to one of two treatment arms. Patients are stratified according to rituximab administration during induction (yes vs no), quality of the response (complete vs partial remission vs no change/progressive disease), and participating center.

    • Arm I: Patients receive no further therapy.
    • Arm II: Beginning 8 weeks after the last CHOP course, patients receive rituximab IV once every 3 months for up to 2 years in the absence of disease progression or unacceptable toxicity.

Patients are followed every 3 months for 2 years and then every 4 months thereafter.

PROJECTED ACCRUAL: A total of 752 patients will be accrued for this study within 6 years.

Study Design

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 475 participants
Allocation: Randomized
Primary Purpose: Treatment
Official Title: Chimeric Anti-CD20 Monoclonal Antibody (Mabthera) in Remission Induction and Maintenance Treatment of Relapsed Follicular Non-Hodgkin's Lymphoma: A Phase III Randomized Clinical Trial - Intergroup Collaborative Study
Study Start Date : May 1999
Primary Completion Date : April 2004
Study Completion Date : July 19, 2017

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Lymphoma
U.S. FDA Resources

Arms and Interventions

Outcome Measures

Primary Outcome Measures :
  1. Response to treatment

Secondary Outcome Measures :
  1. Overall survival [ Time Frame: from randomization ]
  2. Progression Free survival [ Time Frame: from randomization ]

Eligibility Criteria

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 120 Years   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No


  • Histologically or cytologically proven stage III or IV follicular non-Hodgkin's lymphoma (NHL)

    • Relapsed after or no response (no change/progressive disease) to no more than 2 adequate non-anthracycline-containing systemic chemotherapy regimens
    • At least 2 months of single-agent therapy (e.g., chlorambucil) AND/OR
    • At least 2 consecutive courses of polychemotherapy (e.g., cyclophosphamide, vincristine, and prednisone) or purine analogues
  • Complete or partial remission or no change for at least 4 weeks after completion of prior therapy OR progression during one of a maximum of 2 prior therapy regimens
  • CD20 positive
  • At least 1 bidimensionally measurable mass
  • No greater than 10,000,000/mL circulating tumor cells
  • IgG levels at least 3 g/L
  • No low-grade NHL transformed into intermediate- or high-grade NHL
  • No symptomatic CNS lymphoma
  • No bone marrow involvement only NOTE: A new classification scheme for adult non-Hodgkin's lymphoma has been adopted by PDQ. The terminology of "indolent" or "aggressive" lymphoma will replace the former terminology of "low", "intermediate", or "high" grade lymphoma. However, this protocol uses the former terminology.



  • 18 and over

Performance status:

  • WHO 0-2

Life expectancy:

  • Not specified


  • Not specified


  • Bilirubin less than 2.5 times upper limit of normal (ULN)
  • Alkaline phosphatase less than 2.5 times ULN


  • Creatinine less than 2.5 times ULN
  • BUN less than 2.5 times ULN


  • No severe cardiac disease (i.e., severe heart failure requiring symptomatic treatment)


  • No severe pulmonary disease


  • No severe neurologic or psychiatric disease
  • No severe metabolic disease
  • Not pregnant
  • Fertile patients must use effective contraception
  • No prior malignancy within the past 5 years except nonmelanomatous skin cancer, carcinoma in situ of the cervix, or other cancer curatively treated with surgical therapy
  • HIV negative
  • No uncontrolled asthma or allergy requiring steroids
  • No known hypersensitivity or prior anaphylactic reaction to murine proteins or any component of study drug


Biologic therapy:

  • No prior rituximab
  • No prior allogeneic or autologous peripheral blood stem cell transplantation
  • Concurrent filgrastim (G-CSF) for stem cell mobilization allowed


  • See Disease Characteristics
  • No prior anthracyclines or mitoxantrone
  • No concurrent chemotherapy for stem cell mobilization

Endocrine therapy:

  • Not specified


  • Not specified


  • Not specified
Contacts and Locations

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00004179

  Show 261 Study Locations
Sponsors and Collaborators
European Organisation for Research and Treatment of Cancer - EORTC
Lymphoma Trials Office
Stichting Hemato-Oncologie voor Volwassenen Nederland
Australasian Leukaemia and Lymphoma Group
NCIC Clinical Trials Group
Nordic Lymphoma Group
Study Chair: M. H. J. Van Oers, MD Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
Study Chair: Robert Marcus, MD Cambridge University Hospitals NHS Foundation Trust
Study Chair: Max M. Wolf, MD Peter MacCallum Cancer Centre, Australia
Study Chair: Richard J. Klasa, MD British Columbia Cancer Agency
Study Chair: Eva K. Kimby, MD, PhD Karolinska Institutet
More Information

Pompen M, Huijgens PC, et al.: Cost-effectiveness of rituximab for maintenance in patients with follicular non-Hodgkin's lymphoma in the Dutch setting. [Abstract] Blood 112 (11): A-2364, 2008.

Responsible Party: European Organisation for Research and Treatment of Cancer - EORTC
ClinicalTrials.gov Identifier: NCT00004179     History of Changes
Other Study ID Numbers: EORTC-20981
EORTC-20981 ( Other Identifier: EORTC )
ALLG-NHLLOW4 ( Other Identifier: ALLG )
BNLI-EORTC-20981 ( Other Identifier: BNLI )
HOVON-H039 ( Other Identifier: HOVON )
CAN-NCIC-LY7 ( Other Identifier: NCIC CTG )
NORDIC-EORTC-20981 ( Other Identifier: NLG )
First Posted: January 27, 2003    Key Record Dates
Last Update Posted: July 27, 2017
Last Verified: July 2017

Keywords provided by European Organisation for Research and Treatment of Cancer - EORTC:
stage III grade 1 follicular lymphoma
stage III grade 2 follicular lymphoma
stage III grade 3 follicular lymphoma
stage IV grade 1 follicular lymphoma
stage IV grade 2 follicular lymphoma
stage IV grade 3 follicular lymphoma
recurrent grade 1 follicular lymphoma
recurrent grade 2 follicular lymphoma
recurrent grade 3 follicular lymphoma

Additional relevant MeSH terms:
Lymphoma, Non-Hodgkin
Neoplasms by Histologic Type
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Liposomal doxorubicin
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists
Antibiotics, Antineoplastic
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Anti-Inflammatory Agents