Pegfilgrastim and Combination Chemotherapy With or Without Rituximab in Treating Older Patients With Aggressive B-Cell Non-Hodgkin Lymphoma

Sponsor

Universität des Saarlandes (Other)

Overall Status

Completed

CT.gov ID

NCT00726700

Collaborator

(none)

109

Enrollment

Arms

Duration (Months)

Study Details

Study Description

Brief Summary

RATIONALE: Drugs used in chemotherapy, such as cyclophosphamide, doxorubicin, and vincristine, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Colony-stimulating factors, such as pegfilgrastim, may increase the number of immune cells found in bone marrow or peripheral blood and may help the immune system recover from the side effects of chemotherapy. Monoclonal antibodies, such as rituximab, can block cancer growth in different ways. Some find cancer cells and kill them or carry cancer-killing substances to them. Others interfere with the ability of cancer cells to grow and spread. It is not yet known whether combination chemotherapy and pegfilgrastim is more effective when given with or without rituximab in treating non-Hodgkin lymphoma.

PURPOSE: This phase II trial is studying the side effects of giving pegfilgrastim and combination chemotherapy together with or without rituximab and to see how well it works in treating older patients with aggressive B-cell non-Hodgkin lymphoma.

Condition or Disease	Intervention/Treatment	Phase
Lymphoma	Biological: pegfilgrastim Biological: rituximab Drug: cyclophosphamide Drug: doxorubicin hydrochloride Drug: prednisone Drug: vincristine sulfate	Phase 2

Detailed Description

OBJECTIVES:

Determine the side effects of pegfilgrastim and cyclophosphamide, doxorubicin hydrochloride, vincristine, and prednisone (CHOP) with or without rituximab in older patients with aggressive B-cell non-Hodgkin lymphoma.
Determine adherence to therapy regimens in these patients.
Determine antitumor effectivity of immunochemotherapy.

OUTLINE: This is a multicenter study.

All patients receive prephase treatment comprising vincristine on day -6 and prednisone on days -6 to 0. Patients are then randomized to 1 of 2 treatment arms.

Arm I (without rituximab): Patients receive pegfilgrastim subcutaneously (SC) on day 2 or 4 and CHOP comprising cyclophosphamide IV, doxorubicin hydrochloride IV, and vincristine IV on day 1, and oral prednisone on days 1-5. Treatment repeats every 2 weeks for up to 6-8 courses in the absence of disease progression or unacceptable toxicity.
Arm II (with rituximab): Patients receive pegfilgrastim and CHOP for up to 6-8 courses as in arm I. They also receive rituximab (administered 2 hours before beginning CHOP) on day 1. Treatment with rituximab repeats every 2 weeks for up to 8 courses.

Patients with bulky disease or extranodal disease also undergo radiotherapy.

Study Design

Study Type:

Interventional

Actual Enrollment :

109 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Primary Purpose:

Treatment

Official Title:

Randomized Phase II Study About the Application of Pegfilgrastim (Neulasta) at Day 2 or Day 4 Within the Treatment in Patients With Aggressive Non-Hodgkin's Lymphoma Aged 61 to 80 Years With 6 or 8 Cycles of Chemotherapy With CHOP (Cyclophosphamide, Doxorubicin, Vincristine and Prednisone) at 14-day Intervals (CHOP-14), Both With or Without the Monoclonal Anti-CD20 Antibody Rituximab

Study Start Date :

May 1, 2004

Actual Primary Completion Date :

Feb 1, 2012

Actual Study Completion Date :

Feb 1, 2012

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Arm I (without rituximab) Patients receive pegfilgrastim subcutaneously (SC) on day 2 or 4 and CHOP comprising cyclophosphamide IV, doxorubicin IV, vincristine IV on day 1, and oral prednisone on days 1-5. Treatment repeats every 2 weeks for up to 6-8 courses in the absence of disease progression or unacceptable toxicity.	Biological: pegfilgrastim Given subcutaneously Drug: cyclophosphamide Given IV Drug: doxorubicin hydrochloride Given IV Drug: prednisone Given orally Drug: vincristine sulfate Given IV
Experimental: Arm II (with rituximab) Patients receive pegfilgrastim and CHOP for up to 6-8 courses as in arm I. They also receive rituximab (administered 2 hours before beginning CHOP) on day 1. Treatment with rituximab repeats every 2 weeks for up to 8 courses.	Biological: pegfilgrastim Given subcutaneously Biological: rituximab Given IV Drug: cyclophosphamide Given IV Drug: doxorubicin hydrochloride Given IV Drug: prednisone Given orally Drug: vincristine sulfate Given IV

Arm

Intervention/Treatment

Active Comparator: Arm I (without rituximab)

Patients receive pegfilgrastim subcutaneously (SC) on day 2 or 4 and CHOP comprising cyclophosphamide IV, doxorubicin IV, vincristine IV on day 1, and oral prednisone on days 1-5. Treatment repeats every 2 weeks for up to 6-8 courses in the absence of disease progression or unacceptable toxicity.

Biological: pegfilgrastim

Given subcutaneously

Drug: cyclophosphamide

Given IV

Drug: doxorubicin hydrochloride

Given IV

Drug: prednisone

Given orally

Drug: vincristine sulfate

Given IV

Experimental: Arm II (with rituximab)

Patients receive pegfilgrastim and CHOP for up to 6-8 courses as in arm I. They also receive rituximab (administered 2 hours before beginning CHOP) on day 1. Treatment with rituximab repeats every 2 weeks for up to 8 courses.

Biological: pegfilgrastim

Given subcutaneously

Biological: rituximab

Given IV

Drug: cyclophosphamide

Given IV

Drug: doxorubicin hydrochloride

Given IV

Drug: prednisone

Given orally

Drug: vincristine sulfate

Given IV

Outcome Measures

Primary Outcome Measures

comparison of pegfilgrastim day 4 versus day 2 for the prevention of chemotherapy-induced leukocytopenia [through chemotherapy administration (up to 112 days respectively)]
median of two measurements of hemoglobin, leukocyte and platelet counts per chemotherapy cycle per Patient in correlation with median pegfilgrastim serum levels at day 1 of the next chemotherapy cycle
comparison of pegfilgrastim day 4 versus day 2 for the prevention of chemotherapy-induced leukocytopenia [through chemotherapy administration (up to 112 days respectively)]
rates and grades of leukocytopenias and infections according to NCI-CTC criteria (version 2)

Secondary Outcome Measures

Adherence to therapy regimens [through chemotherapy administration (up to 112 days respectively)]
the median overall treatment duration
Antitumor effectivity [median time of observation up to 3 years]
progression-free survival
Disease-free survival [median time of observation up to 3 years]
period of disease-free survival

Eligibility Criteria

Criteria

Ages Eligible for Study:

61 Years to 80 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

DISEASE CHARACTERISTICS:

Diagnosis of CD20-positive B-cell non-Hodgkin lymphoma (NHL)
Confirmed by an excisional biopsy of a lymph node or by a sufficiently extensive biopsy of an extranodal involvement (if there is no lymph node involvement)
Results of the immunohistological analysis of expression of the CD20 antigen by lymphoma cells must be obtained
Aggressive disease, including any of the following B-cell NHL
Stage III follicular lymphoma
Stage III follicular lymphoma and diffuse B-cell lymphoma
Lymphoblastic precursor B-cell lymphoma
Diffuse large B-cell lymphoma, including any of the following subtypes:
Centroblastic
Immunoblastic
Plasmablastic
Anaplastic large cell
T-cell rich B-cell lymphoma
Primary effusion lymphoma
Intravasal B-cell lymphoma
Primary mediastinal B-cell lymphoma
Mantle zone lymphoma
Burkitt or Burkitt-like lymphoma
Aggressive marginal zone lymphoma (monocytoid)
All risk group allowed
Age adjusted IPI 0-3
Previously untreated disease