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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 : February 15, 2021
Sponsor:
Collaborators:
Lymphoma Trials Office
Stichting Hemato-Oncologie voor Volwassenen Nederland
Australasian Leukaemia and Lymphoma Group
NCIC Clinical Trials Group
Nordic Lymphoma Group
Information provided by (Responsible Party):
European Organisation for Research and Treatment of Cancer - EORTC

Tracking Information
First Submitted Date  ICMJE January 21, 2000
First Posted Date  ICMJE January 27, 2003
Last Update Posted Date February 15, 2021
Actual Study Start Date  ICMJE May 1999
Actual Primary Completion Date April 2004   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: February 3, 2016)
Response to treatment
Original Primary Outcome Measures  ICMJE Not Provided
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: February 3, 2016)
  • Overall survival [ Time Frame: from randomization ]
  • Progression Free survival [ Time Frame: from randomization ]
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 Combination Chemotherapy With or Without Rituximab in Treating Patients With Relapsed Non-Hodgkin's Lymphoma
Official Title  ICMJE 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
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.

Detailed Description

OBJECTIVES:

  • 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 Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Primary Purpose: Treatment
Condition  ICMJE Lymphoma
Intervention  ICMJE
  • Biological: rituximab
  • Drug: CHOP regimen
  • Drug: cyclophosphamide
  • Drug: doxorubicin hydrochloride
  • Drug: prednisone
  • Drug: vincristine sulfate
Study Arms  ICMJE Not Provided
Publications *

*   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
Actual Enrollment  ICMJE
 (submitted: February 10, 2015)
475
Original Enrollment  ICMJE Not Provided
Actual Study Completion Date  ICMJE July 19, 2017
Actual Primary Completion Date April 2004   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

DISEASE CHARACTERISTICS:

  • 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.

PATIENT CHARACTERISTICS:

Age:

  • 18 and over

Performance status:

  • WHO 0-2

Life expectancy:

  • Not specified

Hematopoietic:

  • Not specified

Hepatic:

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

Renal:

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

Cardiovascular:

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

Pulmonary:

  • No severe pulmonary disease

Other:

  • 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

PRIOR CONCURRENT THERAPY:

Biologic therapy:

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

Chemotherapy:

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

Endocrine therapy:

  • Not specified

Radiotherapy:

  • Not specified

Surgery:

  • Not specified
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 120 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 Australia,   Belgium,   Canada,   Denmark,   Egypt,   France,   Hungary,   Italy,   Netherlands,   New Zealand,   Norway,   Poland,   Portugal,   Slovakia,   Slovenia,   South Africa,   Sweden,   United Kingdom
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00004179
Other Study ID Numbers  ICMJE 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 )
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party European Organisation for Research and Treatment of Cancer - EORTC
Study Sponsor  ICMJE European Organisation for Research and Treatment of Cancer - EORTC
Collaborators  ICMJE
  • Lymphoma Trials Office
  • Stichting Hemato-Oncologie voor Volwassenen Nederland
  • Australasian Leukaemia and Lymphoma Group
  • NCIC Clinical Trials Group
  • Nordic Lymphoma Group
Investigators  ICMJE
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
PRS Account European Organisation for Research and Treatment of Cancer - EORTC
Verification Date February 2021

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