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

Lymphoma Clinical Trial

— IDEC-C2B8  

Official title:

Randomized Intergroup Trial of First Line Treatment for Patients With Diffuse Large B-Cell Non-Hodgkin's Lymphoma With a CHOP-Like Chemotherapy Regimen With or Without the Anti-CD20 Antibody Rituximab

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00064116
• Other study ID #: LY9
• Secondary ID: CAN-NCIC-LY9ROCH
• Status: Completed
• Phase: Phase 3
• Start date: May 8, 2001
• Est. completion date: January 16, 2014

Study information

• Verified date: March 2020
• Source: Canadian Cancer Trials Group
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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 combination chemotherapy is more effective with or without rituximab in treating patients with non-Hodgkin's lymphoma.

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

Description:

OBJECTIVES:

• Compare the time to treatment failure in patients with CD20-positive diffuse large B-cell non-Hodgkin's lymphoma treated with CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone)-like chemotherapy with vs without rituximab.

• Compare the tumor control, progression rate, and complete remission rate in patients treated with these regimens.

• Compare the disease-free and overall survival rate of patients treated with these regimens.

• Compare the toxicity of these regimens in these patients.

OUTLINE: This is a randomized, open-label, multicenter study. Patients are stratified according to participating center, bulky disease (no vs yes), International Prognostic Index score (0 vs 1), and chemotherapy (CHOP vs CHOEP vs PMitCEBO vs MACOP-B). Patients are randomized to 1 of 2 treatment arms.

• Arm I: Patients receive 1 of the following chemotherapy regimens according to participating country:

• CHOP: Patients receive cyclophosphamide IV, doxorubicin IV, and vincristine IV on day 1 and oral prednisone or prednisolone on days 1-5. Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity.

• CHOEP-21: Patients receive cyclophosphamide IV, doxorubicin IV, and vincristine IV on day 1; etoposide IV on days 1-3; and oral prednisone on days 1-5. Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity.

• PMitCEBO: Patients receive mitoxantrone IV, cyclophosphamide IV, and etoposide IV on day 1; vincristine IV and bleomycin IV on day 8; and oral prednisolone daily during weeks 1-4 and every other day during week 5. Treatment repeats every 14 days for 6 courses in the absence of disease progression or unacceptable toxicity.

• MACOP-B: Patients receive cyclophosphamide IV and doxorubicin IV on days 1, 15, 29, 43, 57, and 71; methotrexate IV and vincristine IV on days 8, 36, and 64; bleomycin IV and vincristine IV on days 22, 50, and 78; and oral or intramuscular prednisone on days 1-84. Treatment continues in the absence of disease progression or unacceptable toxicity.

• Arm II: Patients receive arm I regimens (according to participating country) and rituximab as follows:

• CHOP and rituximab: Patients receive CHOP as in arm I and rituximab IV on day 1.

• CHOEP-21 and rituximab: Patients receive CHOEP-21 as in arm I and rituximab IV on day 1.

• PMitCEBO and rituximab: Patients receive PMitCEBO as in arm I and rituximab IV on day 1 during courses 1 and 4; on day 8 during courses 2 and 5; and on day 1 at 1 and 4 weeks after completion of the last course of PMitCEBO chemotherapy.

• MACOP-B and rituximab: Patients receive MACOP-B as in arm I and rituximab IV on days 1, 22, 43, 64, 85, and 106.

Patients are followed every 3 months for 2 years, every 6 months for 3 years, and then annually thereafter.

PROJECTED ACCRUAL: A total of 820 patients will be accrued for this study within approximately 2 years.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 824
• Est. completion date: January 16, 2014
• Est. primary completion date: December 2010
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 60 Years

Eligibility

DISEASE CHARACTERISTICS:

• Histologically confirmed diffuse large B-cell non-Hodgkin's lymphoma according to REAL classification

• Diagnosed within the past 6 weeks

• CD20+ disease

• Ann Arbor stage II, III, or IV disease or stage I bulky disease

• International Prognostic Index (IPI) score of 0 or 1

• Score 0 defined by all of the following:

• Stage I or II disease

• ECOG performance status of 0 or 1

• Lactic dehydrogenase (LDH) no greater than upper limit of normal (ULN)

• Score 1 defined by 1 of the following:

• Stage I or II disease; ECOG performance status of 0 or 1; and LDH greater than ULN

• Stage I or II disease; ECOG performance status 2 or 3; and LDH no greater than ULN

• Stage III or IV disease; ECOG performance status 0 or 1; and LDH no greater than ULN

• Previously untreated disease

• Mediastinal B-cell lymphoma allowed

• No secondary lymphoma after prior chemotherapy or radiotherapy for other malignancies

• No transformed lymphoma

• No primary CNS lymphoma

• No primary gastrointestinal (MALT) lymphoma

• No post-transplant lymphoproliferative disorder

PATIENT CHARACTERISTICS:

Age

• 18 to 60

Performance status

• See Disease Characteristics

• ECOG 0-3

Life expectancy

• At least 3 months

Hematopoietic

• Not specified

Hepatic

• Bilirubin no greater than 2.0 mg/dL*

• Transaminases no greater than 3 times normal*

• No active chronic hepatitis B or C infection NOTE: *Unless related to lymphoma

Renal

• Creatinine no greater than 2 times normal* NOTE: *Unless related to lymphoma

Cardiovascular

• No myocardial infarction within the past 6 months

• No uncompensated heart failure

• No dilatative cardiomyopathy

• No coronary heart disease with ST segment depression on ECG

• No severe uncompensated hypertension

Pulmonary

• No chronic lung disease with hypoxemia

Other

• Not pregnant or nursing

• Negative pregnancy test

• Fertile patients must use effective contraception

• HIV negative

• No known allergic reactions against foreign proteins

• No other prior malignancy except basal cell skin cancer or carcinoma in situ of the cervix

• No concurrent disease that would preclude study treatment

• No active infections requiring systemic antibiotics or antiviral medications

• No severe uncompensated diabetes mellitus

• No clinical signs of cerebral dysfunction

• No severe psychiatric disease

PRIOR CONCURRENT THERAPY:

Biologic therapy

• No prior murine antibodies

Chemotherapy

• No other concurrent anticancer chemotherapy

Endocrine therapy

• Not specified

Radiotherapy

• No concurrent response-adapted (slow response or unconfirmed complete response) radiotherapy

Surgery

• Not specified

Other

• No prior lymphoma-specific treatment

• More than 12 weeks since prior participation in another clinical trial

• No prior participation in this study

• No other concurrent study medication

Related Conditions & MeSH terms

• Lymphoma
• Lymphoma, Non-Hodgkin

Intervention

Biological:
• rituximab
Rituximab 375 mg/m² i.v. day 1

Drug:
• CHOP regimen
Cyclophosphamide 750 mg/m² i.v. day 1 Doxorubicin 50 mg/m² i.v. day 1 Vincristine 2 mg (abs.) i.v. day 1 Prednisone 100 mg/d p.o. days 1 to 5 Recycle day 22 Total number of cycles: 6

Locations

Country	Name	City	State
Canada	Tom Baker Cancer Centre	Calgary	Alberta
Canada	PEI Cancer Treatment Centre,Queen Elizabeth Hospital	Charlottetown	Prince Edward Island
Canada	Cross Cancer Institute	Edmonton	Alberta
Canada	Hopital Charles LeMoyne	Greenfield Park	Quebec
Canada	QEII Health Sciences Center	Halifax	Nova Scotia
Canada	Cancer Centre of Southeastern Ontario at Kingston	Kingston	Ontario
Canada	Grand River Regional Cancer Centre	Kitchener	Ontario
Canada	London Regional Cancer Program	London	Ontario
Canada	The Moncton Hospital	Moncton	New Brunswick
Canada	CHUM - Hopital Notre-Dame	Montreal	Quebec
Canada	Hopital du Sacre-Coeur de Montreal	Montreal	Quebec
Canada	Hopital Maisonneuve-Rosemont	Montreal	Quebec
Canada	McGill University - Dept. Oncology	Montreal	Quebec
Canada	Ottawa Health Research Institute - General Division	Ottawa	Ontario
Canada	CHA-Hopital Du St-Sacrement	Quebec City	Quebec
Canada	Allan Blair Cancer Centre	Regina	Saskatchewan
Canada	Saskatoon Cancer Centre	Saskatoon	Saskatchewan
Canada	Centre hospitalier universitaire de Sherbrooke	Sherbrooke	Quebec
Canada	Niagara Health System	St. Catharines	Ontario
Canada	Dr. H. Bliss Murphy Cancer Centre	St. John's	Newfoundland and Labrador
Canada	Odette Cancer Centre	Toronto	Ontario
Canada	Trillium Health Centre - West Toronto	Toronto	Ontario
Canada	Univ. Health Network-Princess Margaret Hospital	Toronto	Ontario
Canada	Univ. Health Network-The Toronto General Hospital	Toronto	Ontario
Canada	CancerCare Manitoba	Winnipeg	Manitoba

Sponsors (1)

Lead Sponsor	Collaborator
NCIC Clinical Trials Group

Country where clinical trial is conducted

Canada, 

References & Publications (2)

Pfreundschuh M, Ho AD, Cavallin-Stahl E, Wolf M, Pettengell R, Vasova I, Belch A, Walewski J, Zinzani PL, Mingrone W, Kvaloy S, Shpilberg O, Jaeger U, Hansen M, Corrado C, Scheliga A, Loeffler M, Kuhnt E; MabThera International Trial (MInT) Group. Prognos — View Citation

Pfreundschuh M, Trümper L, Osterborg A, Pettengell R, Trneny M, Imrie K, Ma D, Gill D, Walewski J, Zinzani PL, Stahel R, Kvaloy S, Shpilberg O, Jaeger U, Hansen M, Lehtinen T, López-Guillermo A, Corrado C, Scheliga A, Milpied N, Mendila M, Rashford M, Kuh — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Time to treatment failure (TTF) at 3 years		3 years
Secondary	Complete remission rate after completion of treatment		3 years
Secondary	Overall survival at 3 years		3 years
Secondary	Tumor control measured by TTF with non-tumor events censored at 3 years		3 years
Secondary	Disease-free survival (DFS) measured by TTF after an event during and directly after treatment at 3 years		3 years
Secondary	Progression rate determined by dividing the number of patients with disease progression by number of patients with evaluable outcome at 3 years		3 years
Secondary	Time to progression measured at 3 years		3 years
Secondary	Toxicity assessed by NCI CTC v2.0 after completion of treatment		3 years