Clinical trial NCT00004112: Combination Chemotherapy With or Without Rituximab in Treating Patients With Newly Diagnosed Non-Hodgkin's Lymphoma
Official title: A Phase III Randomized Trial of CHOP Chemotherapy Plus Rituxan (IDEC-C2B8) Versus CHOP Chemotherapy Alone for Newly Diagnosed, Previously Untreated, Aggressive Non-Hodgkin's Lymphoma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Lymphoma
Keywords: stage II adult diffuse small cleaved cell lymphoma
stage II adult diffuse mixed cell lymphoma
stage II adult diffuse large cell lymphoma
stage III adult diffuse small cleaved cell lymphoma
stage III adult diffuse mixed cell lymphoma
stage III adult diffuse large cell lymphoma
stage IV adult diffuse small cleaved cell lymphoma
stage IV adult diffuse mixed cell lymphoma
stage IV adult diffuse large cell lymphoma
stage III mantle cell lymphoma
stage IV mantle cell lymphoma
anaplastic large cell lymphoma
stage II mantle cell lymphoma
stage II small lymphocytic lymphoma
stage II marginal zone lymphoma
stage III small lymphocytic lymphoma
stage III marginal zone lymphoma
stage IV small lymphocytic lymphoma
stage IV marginal zone lymphoma
extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue
nodal marginal zone B-cell lymphoma
splenic marginal zone lymphoma
Lead sponsor: University of Nebraska
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2004-05-25
Sex: ALL
Minimum age (years): 19
Maximum age (years): 120
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Primary purpose: TREATMENT

Brief 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 plus rituximab is more effective than combination chemotherapy alone for non-Hodgkin's lymphoma.

PURPOSE: Randomized phase III trial to compare the effectiveness of combination chemotherapy with or without rituximab in treating patients who have newly diagnosed non-Hodgkin's lymphoma that has not been treated previously.

Detailed description: OBJECTIVES: I. Determine whether the addition of rituximab to cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) increases the failure-free survival of patients with newly diagnosed, previously untreated, aggressive B-cell non-Hodgkin's lymphoma. II. Determine whether the addition of rituximab changes the toxicity profile attributed to CHOP chemotherapy in this patient population.

OUTLINE: This is a randomized, multicenter study. Patients are stratified by center, histology (diffuse small cleaved cell, diffuse mixed, and diffuse large cell vs immunoblastic large cell, mantle cell, and marginal zone), and risk group (low vs intermediate vs high). Patients enter one of two treatment arms: Arm I: Patients receive rituximab IV on day 1, followed by cyclophosphamide IV, doxorubicin IV, vincristine IV, and oral prednisone for 5 consecutive days beginning on day 3. Arm II: Patients receive cyclophosphamide IV, doxorubicin IV, vincristine IV, and oral prednisone daily for 5 consecutive days beginning on day 1. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. Patients will be followed for 3 years.

PROJECTED ACCRUAL: A total of 270 patients (135 per treatment arm) will be accrued for this study within 3 years.

Eligibility criteria: Inclusion Criteria:

* Histologically confirmed, newly diagnosed, aggressive (stage II-IV) B-cell non-Hodgkin's lymphoma, including but not limited to:

  * Mantle cell
  * Diffuse large cell
  * Diffuse mixed cell
  * Anaplastic large cell (B-cell type)
  * Diffuse small cleaved cell
  * Marginal zone lymphoma
  * CD20 positive
* 19 years old and over
* WHO 0-2
* Karnofsky 70-100%
* Life expectancy at least 6 months
* Absolute neutrophil count greater than 1,000/mm3 (unless due to non-Hodgkin's lymphoma (NHL) bone marrow involvement)
* Bilirubin less than 3.0 mg/dL
* Alkaline phosphatase less than 3 times upper limit of normal (ULN)
* SGOT less than 3 times ULN
* Fertile patients must use effective contraception
* HIV negative
* Nonsteroidal hormones for non-lymphoma related conditions allowed (e.g., insulin for diabetes)

Exclusion Criteria:

* No prior T-cell lymphoma
* Not pregnant or nursing
* No other serious disease or medical condition that would interfere with compliance
* No other concurrent chemotherapy
* No concurrent corticosteroids (unless for prevention of nausea or vomiting)
* No concurrent radiotherapy No other concurrent investigational agents

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Jonsson Comprehensive Cancer Center, UCLA
state: California
city: Omaha
country: United States
facility: University of Nebraska Medical Center
state: Nebraska
Study officials:
affiliation: University of Nebraska
name: Julie M Vose, MD
role: STUDY_CHAIR
References: