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

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
NCIC Clinical Trials Group
ClinicalTrials.gov Identifier:
NCT00064116
First received: July 8, 2003
Last updated: June 20, 2013
Last verified: May 2012

July 8, 2003
June 20, 2013
May 2001
December 2010   (final data collection date for primary outcome measure)
Time to treatment failure (TTF) at 3 years [ Time Frame: 3 years ] [ Designated as safety issue: No ]
Not Provided
Complete list of historical versions of study NCT00064116 on ClinicalTrials.gov Archive Site
  • 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 ]
Not Provided
Not Provided
Not Provided
 
Combination Chemotherapy With or Without Rituximab in Treating Patients With Non-Hodgkin's Lymphoma
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)

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.

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.

Interventional
Phase 3
Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Lymphoma
  • 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
  • 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
    Intervention: Drug: CHOP regimen
  • 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
    Interventions:
    • Biological: rituximab
    • Drug: CHOP regimen

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Active, not recruiting
824
December 2013
December 2010   (final data collection date for primary outcome measure)

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
Both
18 Years to 60 Years
No
Contact information is only displayed when the study is recruiting subjects
Canada
 
NCT00064116
LY9, CAN-NCIC-LY9, ROCHE-CAN-NCIC-LY9, MINT-M39045, CDR0000309053
Yes
NCIC Clinical Trials Group
NCIC Clinical Trials Group
Not Provided
Study Chair: Kevin Imrie, MD Edmond Odette Cancer Centre at Sunnybrook
NCIC Clinical Trials Group
May 2012

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP