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

The recruitment status of this study is unknown because the information has not been verified recently.
Verified January 2006 by National Cancer Institute (NCI).
Recruitment status was  Active, not recruiting
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:
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00004179
First received: January 21, 2000
Last updated: May 7, 2010
Last verified: January 2006
  Purpose

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 Intervention Phase
Lymphoma
Biological: rituximab
Drug: CHOP regimen
Drug: cyclophosphamide
Drug: doxorubicin hydrochloride
Drug: prednisone
Drug: vincristine sulfate
Phase 3

Study Type: Interventional
Study Design: 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

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Response as assessed by modified Lexcor criteria after induction therapy [ Designated as safety issue: No ]
  • Progression-free survival after maintenance therapy [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Overall survival [ Designated as safety issue: No ]
  • Event-free survival after induction therapy [ Designated as safety issue: No ]
  • Time to new lymphoma treatment after maintenance therapy [ Designated as safety issue: No ]

Study Start Date: May 1999
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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: 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
Investigators
Investigator: 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: M. H. J. Van Oers, MD Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
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

Additional Information:
Publications:
van Oers MHJ, van Glabbeke M, Baila L, et al.: Rituximab maintenance treatment of relapsed/resistant follicular non- Hodgkin's lymphoma: long-term outcome of the EORTC 20981 phase III randomized intergroup study. [Abstract] Blood 112 (11): A-836, 2008.
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.
Van Oers MHJ, Van Glabbeke M, Teodorovic I, et al.: Chimeric anti-CD20 monoclonal antibody (rituximab; mabtheraâ) in remission induction and maintenance treatment of relapsed /resistant follicular non-Hodgkin's lymphoma: a phase III randomized intergroup clinical trial. [Abstract] Blood 104 (11): A-586, 2004.

ClinicalTrials.gov Identifier: NCT00004179     History of Changes
Other Study ID Numbers: CDR0000067393, EORTC-20981, ALLG-NHLLOW4, BNLI-EORTC-20981, HOVON-H039, CAN-NCIC-LY7, NORDIC-EORTC-20981
Study First Received: January 21, 2000
Last Updated: May 7, 2010
Health Authority: United States: Federal Government

Keywords provided by National Cancer Institute (NCI):
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
Lymphoma, Follicular
Lymphoma, Non-Hodgkin
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Antibodies, Monoclonal
Cyclophosphamide
Rituximab
Liposomal doxorubicin
Doxorubicin
Prednisone
Vincristine
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Immunosuppressive Agents
Antirheumatic Agents
Therapeutic Uses
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists
Antibiotics, Antineoplastic
Topoisomerase II Inhibitors
Topoisomerase Inhibitors

ClinicalTrials.gov processed this record on August 28, 2014