Lymphocyte Reconstitution After Administration of Pegfilgrastim Versus Filgrastim After Peripheral Stem Cell Transplantation

Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to describe the kinetics of lymphocyte subsets reconstitution after growth factor administration, Pegfilgrastim versus Filgrastim in patients with B-cell malignant non-Hodgkin lymphoma treated with high-dose chemotherapy and autologous peripheral stem cell transplantation.

Detailed Description
-----------------
High dose chemotherapy with autologous peripheral stem cell transplantation is a standard consolidation treatment used in patients with non-Hodgkin lymphoma, in first or second line of treatment. This procedure is associated with prolonged neutropenia and considerable morbidity. Different guidelines have recommended the use of growth factor after peripheral stem cell transplantation.Pegfilgrastim is a granulocyte colony-stimulating factor (G-CSF) resulting from the modification of Filgrastim by chemical addition of a polyethylene glycol(PEG) moiety which increases its half-life by decreasing its renal clearance. Then, a single injection substitutes several Filgrastim injections. The trial PALM realized by our team has shown, between these 2 molecules, an equivalent efficacy on the duration of chemotherapy-induced febrile neutropenia in patients treated for lymphoma or myeloma. This trial has also shown that Pegfilgrastim is a cost-effectiveness dominant strategy. Some studies have shown that a rapid lymphocyte reconstitution after stem cell transplantation is associated with better overall survival and progression-free survival. In the present PALM2 study, the investigators want to describe the kinetics of different lymphocyte subsets reconstitution within 3 and 6 months after transplantation, in patients with B-cell malignant non-Hodgkin lymphoma, in first or second-line chemotherapy and first autologous transplantation. The investigators will assess the kinetics of reconstitution for T-lymphocytes (Naïve T-lymphocytes, regulatory T-cells and memory T-cells), B-lymphocytes (transitional B cells), cytotoxic T-cells and natural killer T-cells, dendritic cells. A preliminary phase to this assessment will consist in estimate intra-center variability of lymphocyte phenotyping.

Official Title
-----------------
Lymphocyte Reconstitution in a Randomized Study After Administration of Pegfilgrastim Versus Filgrastim in Patients With B-cell Non-Hodgkin Lymphoma Treated With High-dose Chemotherapy and Autologous Peripheral Stem Cell Transplantation

Conditions
-----------------
Non Hodgkin Lymphoma

Intervention / Treatment
-----------------
* Drug: Pegfilgrastim
* Drug: Filgrastim


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Age ≥ 18 years. Patients with B-cell NHL, except Burkitt Lymphoma and primary brain lymphoma, as first-line or second-line therapy, with planed BICNU, etoposide, aracytine and melphalan (BEAM) chemotherapy after pre-inclusion. Minimum one mobilization with G-CSF, G-CSF and endoxan or mozobil Minimum one cytapheresis with CD34>2 millions CD34/kg for stem cell transplantation Patients hospitalized in the investigational center throughout the procedure and until recovery from aplasia (neutrophils> 0.5 G/L) Mandatory affiliation with a health insurance system Subjects must provide written informed consent prior to performance of study-specific assessments Exclusion Criteria: Patients already treated with intensive chemotherapy and autologous stem cell transplantation Total irradiation exposure (patients with partial irradiation exposure can be included in the study) Intolerance to one of the two studied growth factors, or hypersensitivity to one of their components Patients with neutropenia (neutrophils <1.2 G/L) or thrombopenia (platelets < 100 G/L) before intensive chemotherapy Acquired immune deficiency syndrome, seropositivity Pregnant or lactating women (pregnancy test, for women of childbearing potential, should be negative, in blood or urine, at inclusion time) Impossibility to comply with protocol constraints because of geographical, psychiatric, social or family reasons Deprived of liberty (court judgement or administrative decision)

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Pegfilgrastim<br> | Drug: Pegfilgrastim<br>* Pegfilgrastim (Neulasta®, AMGEN Laboratories): single subcutaneous administration of Pegfilgrastim, 6 mg at day 5 (D5) after autologous stem cell transplantation<br>* Other names: Neulasta, AMGEN Laboratories;|
| Active Comparator: Filgrastim<br> | Drug: Filgrastim<br>* Filgrastim (Neupogen®, AMGEN Laboratories): daily subcutaneous administration, 5µg/kg/day from day 5 (D5) after autologous stem cell transplantation until recovery from aplasia (Neutrophils >= 0.5 G/L)<br>* Other names: Neupogen, AMGEN Laboratories;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 3 months kinetics of lymphocyte reconstitution, in the two arms |  | Lymphocyte count within the 3 months post transplantation | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 6 months kinetics of lymphocyte reconstitution, in the two arms |  | Lymphocyte count within the 6 months post transplantation | 
| 6 months kinetics of lymphocyte subsets reconstitution by phenotyping, in the 2 arms |  | In the transplant and within the 6 months after transplantation (at Day 15, D30, D90, D180 after transplantation) | 
| Average duration of neutropenia and thrombopenia, in the 2 arms | neutrophils<0.5 G/L neutrophils<1 G/L platelets<20 G/L platelets<50 G/L | Within the 3 months post transplantation | 
| Number of days with temperature ≥38°, in the 2 arms |  | For duration of post transplantation hospital stay, an expected average of 2 weeks | 
| Number of bacterial and/or viral and/or fungal infection longer than 7 days, average duration of anti-viral, anti-fungal and antibiotic treatments, in the 2 arms |  | Within 3 months post transplantation | 
| Number of red blood cell units and platelets concentrates transfused to patient, in the 2 arms |  | Within 3 months post transplantation | 
| Evaluation of duration of Filgrastim treatment, in arm Filgrastim |  | For duration of post transplantation hospital stay, an expected average of 2 weeks | 
| Overall survival |  | Within 18 months after the first inclusion, from the date of randomization until the date of death from any cause | 
| Progression free survival | The progression is measured as per 2007 Cheson international response criteria. Cheson BD et al. Revised response criteria for malignant lymphoma. J of Clin Oncol 2007;25(5):579-586 | Within 18 months after yhe first inclusion, from the date of randomization until the date of the first documented progression or death from any cause, whichever came first | 
| Average duration of febrile neutropenia (with neutrophils<0.5 G/L and temperature ≥38°), in the 2 arms |  | For duration of post transplantation hospital stay, an expected duration of 2 weeks | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Lymphoma, B-cell, Lymphocyte reconstitution, Lymphocyte subsets, Peripheral stem cell transplantation, Induction chemotherapy, growth factor, Granulocyte Colony-stimulating factor, Pegfilgrastim, Filgrastim