Lymphocyte Reconstitution After Administration of Pegfilgrastim Versus Filgrastim After Peripheral Stem Cell Transplantation (PALM2)

This study is currently recruiting participants. (see Contacts and Locations)
Verified March 2014 by Centre Leon Berard
Sponsor:
Collaborator:
Amgen
Information provided by (Responsible Party):
Centre Leon Berard
ClinicalTrials.gov Identifier:
NCT01541072
First received: February 17, 2012
Last updated: March 18, 2014
Last verified: March 2014
  Purpose

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.


Condition Intervention
Non Hodgkin Lymphoma
Drug: Pegfilgrastim
Drug: Filgrastim

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Centre Leon Berard:

Primary Outcome Measures:
  • 3 months kinetics of lymphocyte reconstitution, in the two arms [ Time Frame: Lymphocyte count within the 3 months post transplantation ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • 6 months kinetics of lymphocyte reconstitution, in the two arms [ Time Frame: Lymphocyte count within the 6 months post transplantation ] [ Designated as safety issue: No ]
  • 6 months kinetics of lymphocyte subsets reconstitution by phenotyping, in the 2 arms [ Time Frame: In the transplant and within the 6 months after transplantation (at Day 15, D30, D90, D180 after transplantation) ] [ Designated as safety issue: No ]
  • Average duration of neutropenia and thrombopenia, in the 2 arms [ Time Frame: Within the 3 months post transplantation ] [ Designated as safety issue: No ]
    1. neutrophils<0.5 G/L
    2. neutrophils<1 G/L
    3. platelets<20 G/L
    4. platelets<50 G/L

  • Number of days with temperature ≥38°, in the 2 arms [ Time Frame: For duration of post transplantation hospital stay, an expected average of 2 weeks ] [ Designated as safety issue: No ]
  • 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 [ Time Frame: Within 3 months post transplantation ] [ Designated as safety issue: No ]
  • Number of red blood cell units and platelets concentrates transfused to patient, in the 2 arms [ Time Frame: Within 3 months post transplantation ] [ Designated as safety issue: No ]
  • Evaluation of duration of Filgrastim treatment, in arm "Filgrastim" [ Time Frame: For duration of post transplantation hospital stay, an expected average of 2 weeks ] [ Designated as safety issue: No ]
  • Overall survival [ Time Frame: Within 18 months after the first inclusion, from the date of randomization until the date of death from any cause ] [ Designated as safety issue: No ]
  • Progression free survival [ Time Frame: 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 ] [ Designated as safety issue: No ]
    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

  • Average duration of febrile neutropenia (with neutrophils<0.5 G/L and temperature ≥38°), in the 2 arms [ Time Frame: For duration of post transplantation hospital stay, an expected duration of 2 weeks ] [ Designated as safety issue: No ]

Estimated Enrollment: 60
Study Start Date: February 2012
Estimated Study Completion Date: March 2015
Estimated Primary Completion Date: December 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Pegfilgrastim Drug: Pegfilgrastim
Pegfilgrastim (Neulasta®, AMGEN Laboratories): single subcutaneous administration of Pegfilgrastim, 6 mg at day 5 (D5) after autologous stem cell transplantation
Other Name: Neulasta, AMGEN Laboratories
Active Comparator: Filgrastim Drug: Filgrastim
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)
Other Name: Neupogen, AMGEN Laboratories

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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)
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01541072

Contacts
Contact: Sophie DUSSART +33 478 78 27 52 sophie.dussart@lyon.unicancer.fr

Locations
France
CHU Clermont-Ferrand, Hôpital d'Estaing Recruiting
Clermont-Ferrand, France, 63000
Principal Investigator: Victoria CACHEUX, MD         
Sub-Investigator: Jacques-Olivier BAY, MD         
Sub-Investigator: Olivier TOURNILHAC, MD         
Sub-Investigator: Eric HERMET, MD         
Sub-Investigator: Romain GUIEZE, MD         
Sub-Investigator: Cécile MOLUCON-CHABROT, MD         
Sub-Investigator: Benoît DE RENZIS, MD         
Sub-Investigator: Carine CHATELEIX, MD         
Sub-Investigator: Laure CALVET, MD         
Centre Leon Berard Recruiting
Lyon, France
Contact: Catherine SEBBAN, MD    +33 478 78 28 07    catherine.sebban@lyon.unicancer.fr   
Principal Investigator: Catherine SEBBAN, MD         
Sub-Investigator: Pierre BIRON, MD         
Sub-Investigator: Hervé GHESQUIERES, MD         
Sub-Investigator: Emmanuelle NICOLAS-VIRELIZIER, MD         
Sub-Investigator: Pierre FAURIE, MD         
Sub-Investigator: Amine BELHABRI, MD         
Sub-Investigator: Philippe REY, MD         
Centre Hospitalier Lyon-Sud Not yet recruiting
Pierre-Bénite, France, 69495
Sub-Investigator: Daniel ESPINOUSE, MD         
Sub-Investigator: Bertrand COIFFIER, MD         
Principal Investigator: Gilles SALLES, MD         
Sub-Investigator: Anne-Sophie MICHALLET, MD         
Sub-Investigator: Catherine TRAULLE, MD         
Sub-Investigator: Fadhéla Hind BOUAFIA SAUYV, MD         
Sub-Investigator: Lionel KARLIN, MD         
Sub-Investigator: Laure LEBRAS, MD         
Sponsors and Collaborators
Centre Leon Berard
Amgen
Investigators
Principal Investigator: Catherine SEBBAN, MD Centre Leon Berard, Lyon, France
  More Information

Publications:
Noether, G. E. Sample size determination for some common nonparametric statistics. Journal of the American Statistical Association 82 : 645-47, 1987.

Responsible Party: Centre Leon Berard
ClinicalTrials.gov Identifier: NCT01541072     History of Changes
Other Study ID Numbers: ET2011-010, 2011-A00662-39
Study First Received: February 17, 2012
Last Updated: March 18, 2014
Health Authority: France: The Commission nationale de l’informatique et des libertés
France: Comité consultatif sur le traitement de l'information en matière de recherche dans le domaine de la santé

Keywords provided by Centre Leon Berard:
Lymphoma, B-cell
Lymphocyte reconstitution
Lymphocyte subsets
Peripheral stem cell transplantation
Induction chemotherapy
growth factor
Granulocyte Colony-stimulating factor
Pegfilgrastim
Filgrastim

Additional relevant MeSH terms:
Lymphoma, Non-Hodgkin
Lymphoma
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Lenograstim
Adjuvants, Immunologic
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on October 01, 2014