Clinical trial NCT00726700: Pegfilgrastim and Combination Chemotherapy With or Without Rituximab in Treating Older Patients With Aggressive B-Cell Non-Hodgkin Lymphoma
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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Lymphoma
Keywords: stage III grade 3 follicular lymphoma
stage I adult lymphoblastic lymphoma
stage III adult lymphoblastic lymphoma
stage IV adult lymphoblastic lymphoma
contiguous stage II adult lymphoblastic lymphoma
noncontiguous stage II adult lymphoblastic lymphoma
anaplastic large cell lymphoma
stage III adult diffuse large cell lymphoma
stage I adult diffuse large cell lymphoma
stage IV adult diffuse large cell lymphoma
contiguous stage II adult diffuse large cell lymphoma
contiguous stage II adult immunoblastic large cell lymphoma
noncontiguous stage II adult diffuse large cell lymphoma
noncontiguous stage II adult immunoblastic large cell lymphoma
stage III adult immunoblastic large cell lymphoma
stage I adult immunoblastic large cell lymphoma
stage IV adult immunoblastic large cell lymphoma
stage III adult Burkitt lymphoma
stage IV adult Burkitt lymphoma
stage III mantle cell lymphoma
stage I mantle cell lymphoma
contiguous stage II mantle cell lymphoma
noncontiguous stage II mantle cell lymphoma
stage I adult Burkitt lymphoma
contiguous stage II adult Burkitt lymphoma
noncontiguous stage II adult Burkitt lymphoma
stage III marginal zone lymphoma
stage IV marginal zone lymphoma
stage I marginal zone lymphoma
contiguous stage II marginal zone lymphoma
noncontiguous stage II marginal zone lymphoma
Lead sponsor: Universität des Saarlandes
Sponsor class: OTHER
First posted: 2008-08-01
Enrollment: 109
Sex: ALL
Minimum age (years): 61
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Eligibility criteria: 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

PATIENT CHARACTERISTICS:

* ECOG performance status (PS) 0-2 OR Karnofsky PS 60-100%
* No other serious concurrent diseases

PRIOR CONCURRENT THERAPY:

* See Disease Characteristics

Primary outcomes:
measure: comparison of pegfilgrastim day 4 versus day 2 for the prevention of chemotherapy-induced leukocytopenia
timeFrame: through chemotherapy administration (up to 112 days respectively)
measure: comparison of pegfilgrastim day 4 versus day 2 for the prevention of chemotherapy-induced leukocytopenia
timeFrame: through chemotherapy administration (up to 112 days respectively)
Secondary outcomes:
measure: Adherence to therapy regimens
timeFrame: through chemotherapy administration (up to 112 days respectively)
measure: Antitumor effectivity
timeFrame: median time of observation up to 3 years
measure: Disease-free survival
timeFrame: median time of observation up to 3 years
Other outcomes:
Locations:
Study officials:
affiliation: Universitaetsklinikum des Saarlandes
name: Frank Hartmann, MD
role: STUDY_CHAIR
References:
citation: Zwick C, Hartmann F, Zeynalova S, Poschel V, Nickenig C, Reiser M, Lengfelder E, Peter N, Schlimok G, Schubert J, Schmitz N, Loeffler M, Pfreundschuh M; German High-Grade Non-Hodgkin Lymphoma Study Group. Randomized comparison of pegfilgrastim day 4 versus day 2 for the prevention of chemotherapy-induced leukocytopenia. Ann Oncol. 2011 Aug;22(8):1872-7. doi: 10.1093/annonc/mdq674. Epub 2011 Feb 3.
citation: Muller C, Murawski N, Wiesen MH, Held G, Poeschel V, Zeynalova S, Wenger M, Nickenig C, Peter N, Lengfelder E, Metzner B, Rixecker T, Zwick C, Pfreundschuh M, Reiser M. The role of sex and weight on rituximab clearance and serum elimination half-life in elderly patients with DLBCL. Blood. 2012 Apr 5;119(14):3276-84. doi: 10.1182/blood-2011-09-380949. Epub 2012 Feb 15.