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

Non Hodgkin Lymphoma Clinical Trial

— PALM2  

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01541072
• Other study ID #: ET2011-010
• Secondary ID: 2011-A00662-39
• Status: Terminated
• Phase: N/A
• First received: February 17, 2012
• Last updated: October 31, 2016
• Start date: February 2012
• Est. completion date: September 2014

Study information

• Verified date: October 2016
• Source: Centre Leon Berard
• Contact: n/a
• Is FDA regulated: No
• Health authority: France: The Commission nationale de l’informatique et des libertésFrance: Comité consultatif sur le traitement de l'information en matière de recherche dans le domaine de la santé
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 34
• Est. completion date: September 2014
• Est. primary completion date: June 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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)

Study Design

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

Related Conditions & MeSH terms

• Lymphoma
• Lymphoma, Non-Hodgkin
• Non Hodgkin Lymphoma

Intervention

Drug:
• Pegfilgrastim
Pegfilgrastim (Neulasta®, AMGEN Laboratories): single subcutaneous administration of Pegfilgrastim, 6 mg at day 5 (D5) after autologous stem cell transplantation
• 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)

Locations

Country	Name	City	State
France	CHU Clermont-Ferrand, Hôpital d'Estaing	Clermont-Ferrand
France	Centre Leon Berard	Lyon

Sponsors (2)

Lead Sponsor	Collaborator
Centre Leon Berard	Amgen

Country where clinical trial is conducted

France, 

References & Publications (20)

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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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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

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. — View Citation

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. doi: 10.1016/j.bbmt.2008.04.013. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

Sebban, C., Lefranc, A, Perrier, L., Morreau, P., Espinouse, D., Moles-Moreau, M-P, Kammoun, L, Ghesquieres, H, Segura-Ferlay, C., Bay, J-O, Lissandre, S, PEROL, D, Michallet, M, and Quittet, P. A Randomized Phase II Study Evaluating the Efficacy, Safety and Cost-Effectiveness of Pegfilgrastim and Filgrastim After High Dose Chemotherapy and Autologous Stem Cell Transplantation In Patients with Lymphoma and Myeloma (PALM Study). ASH . 4-12-2010. Ref Type: Abstract

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

Vanstraelen G, Frère P, Ngirabacu MC, Willems E, Fillet G, Beguin Y. Pegfilgrastim compared with Filgrastim after autologous hematopoietic peripheral blood stem cell transplantation. Exp Hematol. 2006 Mar;34(3):382-8. — View Citation

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* Note: There are 20 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	3 months kinetics of lymphocyte reconstitution, in the two arms		Lymphocyte count within the 3 months post transplantation	No
Secondary	6 months kinetics of lymphocyte reconstitution, in the two arms		Lymphocyte count within the 6 months post transplantation	No
Secondary	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)	No
Secondary	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	No
Secondary	Number of days with temperature =38°, in the 2 arms		For duration of post transplantation hospital stay, an expected average of 2 weeks	No
Secondary	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	No
Secondary	Number of red blood cell units and platelets concentrates transfused to patient, in the 2 arms		Within 3 months post transplantation	No
Secondary	Evaluation of duration of Filgrastim treatment, in arm "Filgrastim"		For duration of post transplantation hospital stay, an expected average of 2 weeks	No
Secondary	Overall survival		Within 18 months after the first inclusion, from the date of randomization until the date of death from any cause	No
Secondary	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	No
Secondary	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	No