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

Sponsors and Collaborators:	European Organization for Research and Treatment of Cancer Lymphoma Trials Office Stichting Hemato-Oncologie voor Volwassenen Nederland Australasian Leukaemia and Lymphoma Group (ALLG) National Cancer Institute of Canada Nordic Lymphoma Group
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00004179

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 III

MedlinePlus related topics: Cancer Lymphoma

Drug Information available for: Cyclophosphamide Prednisone Vincristine Doxorubicin Doxorubicin hydrochloride Myocet Rituximab Vincristine sulfate

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Randomized, Active Control
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

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

Please refer to this study by its ClinicalTrials.gov identifier: NCT00004179

Show 261 Study Locations

Sponsors and Collaborators

European Organization for Research and Treatment of Cancer

Lymphoma Trials Office

Stichting Hemato-Oncologie voor Volwassenen Nederland

Australasian Leukaemia and Lymphoma Group (ALLG)

National Cancer Institute of Canada

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 University Hospital - Huddinge

More Information

Additional Information:

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

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.

van Oers MH, Klasa R, Marcus RE, Wolf M, Kimby E, Gascoyne RD, Jack A, Van't Veer M, Vranovsky A, Holte H, van Glabbeke M, Teodorovic I, Rozewicz C, Hagenbeek A. Rituximab maintenance improves clinical outcome of relapsed/resistant follicular non-Hodgkin lymphoma in patients both with and without rituximab during induction: results of a prospective randomized phase 3 intergroup trial. Blood. 2006 Nov 15;108(10):3295-301. Epub 2006 Jul 27.

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.

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:	February 6, 2009
ClinicalTrials.gov Identifier:	NCT00004179 History of Changes
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

Study placed in the following topic categories:

Anti-Inflammatory Agents
Prednisone
Immunologic Factors
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Lymphoma, Follicular
Cyclophosphamide
Follicular Lymphoma
Hormones
Lymphoma, Small Cleaved-cell, Diffuse
Antibodies, Monoclonal
Anti-Bacterial Agents
Lymphoma
Alkylating Agents
Immunoglobulins

Immunoproliferative Disorders
Antineoplastic Agents, Hormonal
Rituximab
Vincristine
Antimitotic Agents
Immunosuppressive Agents
Glucocorticoids
Doxorubicin
Recurrence
Lymphatic Diseases
Antibodies
Tubulin Modulators
Antineoplastic Agents, Alkylating
Lymphoproliferative Disorders
Lymphoma, Non-Hodgkin

Additional relevant MeSH terms:

Anti-Inflammatory Agents
Prednisone
Immunologic Factors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Physiological Effects of Drugs
Hormones, Hormone Substitutes, and Hormone Antagonists
Lymphoma, Follicular
Cyclophosphamide
Antibiotics, Antineoplastic
Hormones
Therapeutic Uses
Lymphoma
Alkylating Agents
Immunoproliferative Disorders

Neoplasms by Histologic Type
Antineoplastic Agents, Hormonal
Immune System Diseases
Rituximab
Mitosis Modulators
Vincristine
Antimitotic Agents
Glucocorticoids
Immunosuppressive Agents
Doxorubicin
Pharmacologic Actions
Lymphatic Diseases
Neoplasms
Tubulin Modulators
Myeloablative Agonists

ClinicalTrials.gov processed this record on May 07, 2009