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 (IDEC-C2B8)
18 Years
60 Years
Both
Lymphoma
Trial Information
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 (IDEC-C2B8)
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.
Inclusion Criteria
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
Type of Study:
Interventional
Study Design:
Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Outcome Measure:
Time to treatment failure (TTF) at 3 years
Outcome Time Frame:
3 years
Safety Issue:
No
Principal Investigator
Kevin Imrie, MD
Investigator Role:
Study Chair
Investigator Affiliation:
Edmond Odette Cancer Centre at Sunnybrook
Authority:
Canada: Health Canada
Study ID:
LY9
NCT ID:
NCT00064116
Start Date:
May 2001
Completion Date:
December 2013
Related Keywords:
- Lymphoma
- stage I adult diffuse large cell lymphoma
- contiguous stage II adult diffuse large cell lymphoma
- noncontiguous stage II adult diffuse large cell lymphoma
- stage III adult diffuse large cell lymphoma
- stage IV adult diffuse large cell lymphoma
- Lymphoma
- Lymphoma, Non-Hodgkin
- Lymphoma, B-Cell
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