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

Sponsor:	NCIC Clinical Trials Group
Information provided by:	NCIC Clinical Trials Group
ClinicalTrials.gov Identifier:	NCT00064116

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 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.

Condition	Intervention	Phase
Lymphoma	Biological: rituximab Drug: CHOP regimen	Phase III

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Efficacy Study Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment
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 (IDEC-C2B8)

Resource links provided by NLM:

MedlinePlus related topics: Cancer Lymphoma

Drug Information available for: Cyclophosphamide Rituximab

U.S. FDA Resources

Further study details as provided by NCIC Clinical Trials Group:

Primary Outcome Measures:

Time to treatment failure (TTF) at 3 years [ Time Frame: 3 years ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Complete remission rate after completion of treatment [ Time Frame: 3 years ] [ Designated as safety issue: No ]
Overall survival at 3 years [ Time Frame: 3 years ] [ Designated as safety issue: No ]
Tumor control measured by TTF with non-tumor events censored at 3 years [ Time Frame: 3 years ] [ Designated as safety issue: No ]
Disease-free survival (DFS) measured by TTF after an event during and directly after treatment at 3 years [ Time Frame: 3 years ] [ Designated as safety issue: No ]
Progression rate determined by dividing the number of patients with disease progression by number of patients with evaluable outcome at 3 years [ Time Frame: 3 years ] [ Designated as safety issue: No ]
Time to progression measured at 3 years [ Time Frame: 3 years ] [ Designated as safety issue: No ]
Toxicity assessed by NCI CTC v2.0 after completion of treatment [ Time Frame: 3 years ] [ Designated as safety issue: Yes ]

Estimated Enrollment:	820
Study Start Date:	May 2001
Estimated Study Completion Date:	November 2011
Primary Completion Date:	December 2010 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Active Comparator: Arm A: CHOP-21 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	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
Active Comparator: Arm B: CHOP-21 + Rituximab Rituximab 375 mg/m² i.v. day 1* 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	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

Detailed 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.

Eligibility

Ages Eligible for Study:	18 Years to 60 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00064116

Locations

Canada, Alberta
Tom Baker Cancer Centre
Calgary, Alberta, Canada, T2N 4N2
Cross Cancer Institute
Edmonton, Alberta, Canada, T6G 1Z2
Canada, Manitoba
CancerCare Manitoba
Winnipeg, Manitoba, Canada, R3E 0V9
Canada, New Brunswick
The Moncton Hospital
Moncton, New Brunswick, Canada, E1C 6Z8
Canada, Newfoundland and Labrador
Dr. H. Bliss Murphy Cancer Centre
St. John's, Newfoundland and Labrador, Canada, AIB 3V6
Canada, Nova Scotia
QEII Health Sciences Center
Halifax, Nova Scotia, Canada, B3H 1V7
Canada, Ontario
Cancer Centre of Southeastern Ontario at Kingston
Kingston, Ontario, Canada, K7L 5P9
Grand River Regional Cancer Centre
Kitchener, Ontario, Canada, N2G 1G3
London Regional Cancer Program
London, Ontario, Canada, N6A 4L6
Ottawa Health Research Institute - General Division
Ottawa, Ontario, Canada, K1H 8L6
Niagara Health System
St. Catharines, Ontario, Canada, L2R 7C6
Odette Cancer Centre
Toronto, Ontario, Canada, M4N 3M5
Trillium Health Centre - West Toronto
Toronto, Ontario, Canada, M9C 1A5
Univ. Health Network-Princess Margaret Hospital
Toronto, Ontario, Canada, M5G 2M9
Univ. Health Network-The Toronto General Hospital
Toronto, Ontario, Canada, M5G 2C4
Canada, Prince Edward Island
PEI Cancer Treatment Centre,Queen Elizabeth Hospital
Charlottetown, Prince Edward Island, Canada, C1A 8T5
Canada, Quebec
Hopital Charles LeMoyne
Greenfield Park, Quebec, Canada, J4V 2H1
CHUM - Hopital Notre-Dame
Montreal, Quebec, Canada, H2L 4M1
Hopital du Sacre-Coeur de Montreal
Montreal, Quebec, Canada, H4J 1C5
Hopital Maisonneuve-Rosemont
Montreal, Quebec, Canada, H1T 2M4
McGill University - Dept. Oncology
Montreal, Quebec, Canada, H2W 1S6
CHA-Hopital Du St-Sacrement
Quebec City, Quebec, Canada, G1S 4L8
Centre hospitalier universitaire de Sherbrooke
Sherbrooke, Quebec, Canada, J1H 5N4
Canada, Saskatchewan
Allan Blair Cancer Centre
Regina, Saskatchewan, Canada, S4T 7T1
Saskatoon Cancer Centre
Saskatoon, Saskatchewan, Canada, S7N 4H4

Sponsors and Collaborators

NCIC Clinical Trials Group

Investigators

Study Chair:

Kevin Imrie, MD

Edmond Odette Cancer Centre at Sunnybrook

More Information

Additional Information:

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

Publications:

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. Prognostic significance of maximum tumour (bulk) diameter in young patients with good-prognosis diffuse large-B-cell lymphoma treated with CHOP-like chemotherapy with or without rituximab: an exploratory analysis of the MabThera International Trial Group (MInT) study. Lancet Oncol. 2008 May;9(5):435-44. Epub 2008 Apr 8.

Pfreundschuh M, Trumper 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, Lopez-Guillermo A, Corrado C, Scheliga A, Milpied N, Mendila M, Rashford M, Kuhnt E, Loeffler M; MabThera International Trial Group. CHOP-like chemotherapy plus rituximab versus CHOP-like chemotherapy alone in young patients with good-prognosis diffuse large-B-cell lymphoma: a randomised controlled trial by the MabThera International Trial (MInT) Group. Lancet Oncol. 2006 May;7(5):379-91.

Responsible Party:	Ralph Meyer, M.D, NCIC Clinical Trials Group
ClinicalTrials.gov Identifier:	NCT00064116 History of Changes
Other Study ID Numbers:	LY9, CAN-NCIC-LY9, ROCHE-CAN-NCIC-LY9, MINT-M39045, CDR0000309053
Study First Received:	July 8, 2003
Last Updated:	October 28, 2011
Health Authority:	Canada: Health Canada

Keywords provided by NCIC Clinical Trials Group:

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

Additional relevant MeSH terms:

Lymphoma
Lymphoma, Non-Hodgkin
Lymphoma, B-Cell
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Cyclophosphamide
Rituximab

Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antirheumatic Agents
Therapeutic Uses
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists

ClinicalTrials.gov processed this record on February 09, 2012