Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outcomes
Outline
Published Results
Related Publications
Trial Contact Information
Registry Information

Alternate Title

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

Basic Trial Information

Phase	Type	Status	Age	Sponsor	Protocol IDs
Phase III	Treatment	Closed	18 and over	Other	EORTC-20981 ALLG-NHLLOW4, BNLI-EORTC-20981, HOVON-H039, CAN-NCIC-LY7, NORDIC-EORTC-20981, NCT00004179, LY7

Objectives

1. 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.
2. Compare the event-free survival and overall survival of patients treated with these regimens.
3. Determine the effect of rituximab as maintenance therapy on progression-free survival of these patients.

Entry 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.]

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

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

Expected Enrollment

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

Outcomes

Response as assessed by modified Lexcor criteria after induction therapy
Progression-free survival after maintenance therapy

Overall survival
Event-free survival after induction therapy
Time to new lymphoma treatment after maintenance therapy

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.

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, et al.: 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 108 (10): 3295-301, 2006.[PUBMED Abstract]

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.

Trial Contact Information

Trial Lead Organizations

European Organization for Research and Treatment of Cancer

M. H. J. Van Oers, MD, Study coordinator		Ph: 31-20-566-5785 Email: m.H.vanoers@amc.uva.nl

Lymphoma Trials Office

Robert Marcus, MD, Protocol chair		Ph: 44-1223-217-071

Stichting Hemato-Oncologie voor Volwassenen Nederland

M. H. J. Van Oers, MD, Protocol chair		Ph: 31-20-566-5785 Email: m.H.vanoers@amc.uva.nl

Australasian Leukemia and Lymphoma Group

Max Wolf, MD, Protocol chair		Ph: 61-3-9656-1087 Email: max.wolf@petermac.org

NCIC-Clinical Trials Group

Richard Klasa, MD, Protocol chair		Ph: 604-877-6000 ext. 2730; 800-663-3333 Email: rklasa@bccancer.bc.ca

Nordic Lymphoma Group

Eva Kimby, MD, PhD, Protocol chair		Ph: 46-8-746-1000 Email: eva.kimby@karolinska.se

Registry Information
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
Trial Start Date		1999-05-21
Registered in ClinicalTrials.gov		NCT00004179
Date Submitted to PDQ		1999-10-27
Information Last Verified		2006-01-05

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