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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
NCIC Clinical Trials Group
ClinicalTrials.gov Identifier:
NCT00064116
First received: July 8, 2003
Last updated: June 23, 2014
Last verified: June 2014
  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 3

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:


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 ]

Enrollment: 824
Study Start Date: May 2001
Study Completion Date: January 2014
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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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-The Toronto General Hospital
Toronto, Ontario, Canada, M5G 2C4
Univ. Health Network-Princess Margaret Hospital
Toronto, Ontario, Canada, M5G 2M9
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
Hopital du Sacre-Coeur de Montreal
Montreal, Quebec, Canada, H4J 1C5
Hopital Maisonneuve-Rosemont
Montreal, Quebec, Canada, H1T 2M4
CHUM - Hopital Notre-Dame
Montreal, Quebec, Canada, H2L 4M1
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:
Publications:
Responsible Party: 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: June 23, 2014
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
Immune System Diseases
Immunoproliferative Disorders
Lymphatic Diseases
Lymphoproliferative Disorders
Neoplasms
Neoplasms by Histologic Type
Cyclophosphamide
Rituximab
Alkylating Agents
Antineoplastic Agents
Antineoplastic Agents, Alkylating
Antirheumatic Agents
Immunologic Factors
Immunosuppressive Agents
Molecular Mechanisms of Pharmacological Action
Myeloablative Agonists
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses

ClinicalTrials.gov processed this record on October 21, 2014