Lymphocyte Reconstitution After Administration of Pegfilgrastim Versus Filgrastim After Peripheral Stem Cell Transplantation - Full Text View

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:

MedlinePlus related topics: Lymphoma

Drug Information available for: Filgrastim Lenograstim Granulocyte colony-stimulating factor Pegfilgrastim

U.S. FDA Resources

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:	August 2013
Estimated Primary Completion Date:	May 2013 (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

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 Angers	Not yet recruiting
Angers, France, 49033
Principal Investigator: Mathilde HUNAULT, MD
Sub-Investigator: Norbert IFRAH, MD
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
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
CHU Montpellier, Hôpital Saint-Eloi	Not yet recruiting
Montpellier, France, 34295
Principal Investigator: Philippe QUITTET, MD
CHU Nantes, Hôpital	Not yet recruiting
Nantes, France, 44093
Principal Investigator: Thomas GASTINNE, MD
Sub-Investigator: Philippe MOREAU, MD
Sub-Investigator: Steven LE GOUILL, MD
Sub-Investigator: Nicolas BLIN, MD
Sub-Investigator: Mohamad MOHTY, MD
Sub-Investigator: Patrice CHEVALIER, MD
Sub-Investigator: Jacques DELAUNAY, MD
Sub-Investigator: Thierry GUILLAUME, 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: Sophie DUPIRE, MD
Sub-Investigator: Anne-Sophie MICHALLET, MD
Sub-Investigator: Florence BROUSSAIS-GUILLAUMOT, MD
Sub-Investigator: Catherine TRAULLE, MD
Sub-Investigator: Fadhéla Hind BOUAFIA SAUYV, MD
Sub-Investigator: Lionel KARLIN, MD
Sub-Investigator: Laure LEBRAS, MD
CHU Tours, Hôpital Bretonneau	Not yet recruiting
Tours, France, 37000
Principal Investigator: Séverine LISSANDRE, MD
Sub-Investigator: Philippe COLOMBAT, MD
Sub-Investigator: Lofti BENBOUBKER, MD
Sub-Investigator: Marc RENAUD, MD
Sub-Investigator: Emmanuel GYAN, MD
Sub-Investigator: Martine DELAIN, MD

Sponsors and Collaborators

Centre Leon Berard

Amgen

Investigators

Principal Investigator:

Catherine SEBBAN, MD

Centre Leon Berard, Lyon, France

More Information

Publications:

Dieckmann D, Plottner H, Berchtold S, Berger T, Schuler G. Ex vivo isolation and characterization of CD4(+)CD25(+) T cells with regulatory properties from human blood. J Exp Med. 2001 Jun 4;193(11):1303-10.

Goguel AF, Crainic K, Ducailar A, Ouin M. Interlaboratory quality assessment of lymphocyte phenotyping. Etalonorme 1990-1992 surveys. Biol Cell. 1993;78(1-2):79-84.

Holmes FA, Jones SE, O'Shaughnessy J, Vukelja S, George T, Savin M, Richards D, Glaspy J, Meza L, Cohen G, Dhami M, Budman DR, Hackett J, Brassard M, Yang BB, Liang BC. Comparable efficacy and safety profiles of once-per-cycle pegfilgrastim and daily injection filgrastim in chemotherapy-induced neutropenia: a multicenter dose-finding study in women with breast cancer. Ann Oncol. 2002 Jun;13(6):903-9.

Holmes FA, O'Shaughnessy JA, Vukelja S, Jones SE, Shogan J, Savin M, Glaspy J, Moore M, Meza L, Wiznitzer I, Neumann TA, Hill LR, Liang BC. Blinded, randomized, multicenter study to evaluate single administration pegfilgrastim once per cycle versus daily filgrastim as an adjunct to chemotherapy in patients with high-risk stage II or stage III/IV breast cancer. J Clin Oncol. 2002 Feb 1;20(3):727-31.

Joao C, Porrata LF, Inwards DJ, Ansell SM, Micallef IN, Johnston PB, Gastineau DA, Markovic SN. Early lymphocyte recovery after autologous stem cell transplantation predicts superior survival in mantle-cell lymphoma. Bone Marrow Transplant. 2006 May;37(9):865-71.

Jonuleit H, Schmitt E, Stassen M, Tuettenberg A, Knop J, Enk AH. Identification and functional characterization of human CD4(+)CD25(+) T cells with regulatory properties isolated from peripheral blood. J Exp Med. 2001 Jun 4;193(11):1285-94.

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

Peggs KS. Immune reconstitution following stem cell transplantation. Leuk Lymphoma. 2004 Jun;45(6):1093-101. Review.

Porrata LF, Gertz MA, Inwards DJ, Litzow MR, Lacy MQ, Tefferi A, Gastineau DA, Dispenzieri A, Ansell SM, Micallef IN, Geyer SM, Markovic SN. Early lymphocyte recovery predicts superior survival after autologous hematopoietic stem cell transplantation in multiple myeloma or non-Hodgkin lymphoma. Blood. 2001 Aug 1;98(3):579-85.

Porrata LF, Inwards DJ, Ansell SM, Micallef IN, Johnston PB, Gastineau DA, Litzow MR, Winters JL, Markovic SN. Early lymphocyte recovery predicts superior survival after autologous stem cell transplantation in non-Hodgkin lymphoma: a prospective study. Biol Blood Marrow Transplant. 2008 Jul;14(7):807-16.

Porrata LF, Inwards DJ, Micallef IN, Ansell SM, Geyer SM, Markovic SN. Early lymphocyte recovery post-autologous haematopoietic stem cell transplantation is associated with better survival in Hodgkin's disease. Br J Haematol. 2002 Jun;117(3):629-33.

Reimer P, Kunzmann V, Wilhelm M, Weissbrich B, Kraemer D, Berghammer H, Weissinger F. Cellular and humoral immune reconstitution after autologous peripheral blood stem cell transplantation (PBSCT). Ann Hematol. 2003 May;82(5):263-70. Epub 2003 Mar 22.

Roberts MM, To LB, Gillis D, Mundy J, Rawling C, Ng K, Juttner CA. Immune reconstitution following peripheral blood stem cell transplantation, autologous bone marrow transplantation and allogeneic bone marrow transplantation. Bone Marrow Transplant. 1993 Nov;12(5):469-75.

Shimizu J, Yamazaki S, Sakaguchi S. Induction of tumor immunity by removing CD25+CD4+ T cells: a common basis between tumor immunity and autoimmunity. J Immunol. 1999 Nov 15;163(10):5211-8.

Singh RK, Ino K, Varney ML, Heimann DG, Talmadge JE. Immunoregulatory cytokines in bone marrow and peripheral blood stem cell products. Bone Marrow Transplant. 1999 Jan;23(1):53-62.

Talmadge JE, Reed E, Ino K, Kessinger A, Kuszynski C, Heimann D, Varney M, Jackson J, Vose JM, Bierman PJ. Rapid immunologic reconstitution following transplantation with mobilized peripheral blood stem cells as compared to bone marrow. Bone Marrow Transplant. 1997 Jan;19(2):161-72.

Thornton AM, Shevach EM. Suppressor effector function of CD4+CD25+ immunoregulatory T cells is antigen nonspecific. J Immunol. 2000 Jan 1;164(1):183-90.

Woo EY, Chu CS, Goletz TJ, Schlienger K, Yeh H, Coukos G, Rubin SC, Kaiser LR, June CH. Regulatory CD4(+)CD25(+) T cells in tumors from patients with early-stage non-small cell lung cancer and late-stage ovarian cancer. Cancer Res. 2001 Jun 15;61(12):4766-72.

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 1, 2013
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
Lymphoma, Non-Hodgkin
Lymphoma, B-Cell
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 May 21, 2013

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