Clinical trial NCT00028717: Combination Chemotherapy Plus Filgrastim With or Without Rituximab in Treating Older Patients With Non-Hodgkin's Lymphoma
Official title: A Randomized Phase III Study Of Chimeric Anti-CD20 Monoclonal Antibody (Rituximab) With 2-Weekly CHOP Chemotherapy In Elderly Patients With Intermediate Or High-Risk Non-Hodgkin's Lymphoma
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE3
Conditions: Lymphoma
Keywords: stage I grade 3 follicular lymphoma
stage I adult diffuse large cell lymphoma
stage III grade 3 follicular lymphoma
stage III adult diffuse large cell lymphoma
stage IV grade 3 follicular lymphoma
stage IV adult diffuse large cell lymphoma
stage I mantle cell lymphoma
contiguous stage II grade 3 follicular lymphoma
contiguous stage II mantle cell lymphoma
contiguous stage II adult diffuse large cell lymphoma
noncontiguous stage II grade 3 follicular lymphoma
noncontiguous stage II mantle cell lymphoma
noncontiguous stage II adult diffuse large cell lymphoma
stage III mantle cell lymphoma
stage IV mantle cell lymphoma
Lead sponsor: National Cancer Institute (NCI)
Sponsor class: NIH
First posted: 2003-01-27
Enrollment: 400
Sex: ALL
Minimum age (years): 65
Standard ages: 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 tumor cells and either kill them or deliver tumor-killing substances to them without harming normal cells. Combining monoclonal antibody therapy with chemotherapy may kill more tumor cells. It is not yet known if combination chemotherapy plus filgrastim is more effective with or without rituximab in treating non-Hodgkin's lymphoma.

PURPOSE: Randomized phase III trial to determine the effectiveness of combination chemotherapy plus filgrastim with or without rituximab in treating older patients who have non-Hodgkin's lymphoma.

Detailed description: OBJECTIVES:

* Compare the efficacy of cyclophosphamide, doxorubicin, vincristine, prednisone (CHOP), and filgrastim (G-CSF) with or without rituximab on event-free survival of elderly patients with intermediate or high-risk non-Hodgkin's lymphoma.
* Compare the complete remission rate, overall survival, and disease-free survival of patients treated with these regimens.
* Compare the toxicity of these regimens in these patients.

OUTLINE: This is a randomized, multicenter study. Patients are stratified according to participating center, WHO classification, and International Prognostic Index score. Patients are randomized to 1 of 2 treatment arms.

* Arm I: Patients receive cyclophosphamide IV, doxorubicin IV, and vincristine IV on day 1; oral prednisone on days 1-5; and filgrastim (G-CSF) subcutaneously on days 1-14. Treatment repeats every 2 weeks for 8 courses in the absence of disease progression or unacceptable toxicity.
* Arm II: Patients receive cyclophosphamide, doxorubicin, vincristine, prednisone, and G-CSF as in arm I. Patients also receive rituximab IV on day 3 of courses 1-2 and on day 1 of courses 3-6 for a total of 6 doses.

Patients are followed every 3 months for 2 years, every 6 months for 2 years, and then annually thereafter.

PROJECTED ACCRUAL: A total of 400 patients (200 per treatment arm) will be accrued for this study within 5 years.

Eligibility criteria: DISEASE CHARACTERISTICS:

* Histologically confirmed non-Hodgkin's lymphoma (NHL)

  * Low- or high-intermediate or high-risk lymphoma of any of the following subtypes:

    * Mantle cell lymphoma
    * Follicular lymphoma (grade III)
    * Diffuse large B-cell lymphoma
* CD20-positive
* No suspected or documented CNS involvement by NHL NOTE: A new classification scheme for adult non-Hodgkin's lymphoma has been adopted by PDQ. The terminology of "indolent" or "aggressive" lymphoma will replace the former terminology of "low", "intermediate", or "high" grade lymphoma. However, this protocol uses the former terminology.

PATIENT CHARACTERISTICS:

Age:

* 65 and over

Performance status:

* WHO 0-2

Life expectancy:

* Not specified

Hematopoietic:

* Not specified

Hepatic:

* Bilirubin less than 1.75 mg/dL\*
* Transaminases less than 2.5 times normal\* NOTE: \* Unless due to NHL

Renal:

* Creatinine less than 1.7 mg/dL (unless due to NHL)

Cardiovascular:

* No severe cardiac dysfunction
* No New York Heart Association class II-IV heart disease
* LVEF at least 45%

Pulmonary:

* No uncontrolled asthma requiring steroid treatment

Other:

* HIV negative
* No intolerance to exogenous protein administration
* No active, uncontrolled infection
* No uncontrolled allergy requiring steroid treatment
* No other malignancy within the past 5 years except basal cell skin cancer or stage 0 cervical cancer

PRIOR CONCURRENT THERAPY:

Biologic therapy:

* No prior immunotherapy for NHL

Chemotherapy:

* No prior chemotherapy for NHL

Endocrine therapy:

* Not specified

Radiotherapy:

* No prior radiotherapy for NHL except local radiotherapy for potential organ dysfunction by localized lymphoma mass or infiltration
* Concurrent local radiotherapy for potential or actual organ dysfunction by localized lymphoma mass or infiltration allowed

Surgery:

* Not specified

Primary outcomes:
measure: Event-free survival
Secondary outcomes:
measure: Complete response
measure: Overall survival
measure: Disease-free interval
measure: Toxicity
Other outcomes:
Locations:
city: 's-Gravenhage
country: Netherlands
facility: HagaZiekenhuis - Locatie Leyenburg
city: Amersfoort
country: Netherlands
facility: Meander Medisch Centrum
city: Amsterdam
country: Netherlands
facility: Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital
city: Amsterdam
country: Netherlands
facility: Vrije Universiteit Medisch Centrum
city: Amsterdam
country: Netherlands
facility: Academisch Medisch Centrum at University of Amsterdam
city: Enschede
country: Netherlands
facility: Medisch Spectrum Twente
city: Groningen
country: Netherlands
facility: University Medical Center Groningen
city: Leiden
country: Netherlands
facility: Leiden University Medical Center
city: Maastricht
country: Netherlands
facility: Academisch Ziekenhuis Maastricht
city: Nieuwegein
country: Netherlands
facility: Sint Antonius Ziekenhuis
city: Rotterdam
country: Netherlands
facility: Daniel Den Hoed Cancer Center at Erasmus Medical Center
city: Utrecht
country: Netherlands
facility: University Medical Center Utrecht
city: Zwolle
country: Netherlands
facility: Isala Klinieken - locatie Sophia
Study officials:
affiliation: Daniel Den Hoed Cancer Center at Erasmus Medical Center
name: Pieter Sonneveld, MD, PhD
role: STUDY_CHAIR
References: