Injection of ex Vivo Amplified G-CSF Mobilised Autologous Peripheral Blood Stem Cell Transplantation - Full Text View

Purpose

Hematopoietic reconstitution defined by a neutrophils number > 500/mm3 at day 7 after injection of ex vivo amplified graft and by a platelets number > 20000/mm3, at day 15 after the injection of ex vivo amplified graft, without transfusion.

Condition	Intervention	Phase
Multiple Myeloma	Procedure: autologous peripheral blood stem cell transplantation, ex vivo amplified	Phase 2

Study Type:	Interventional
Study Design:	Endpoint Classification: Safety/Efficacy Study Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	Pilot Clinical Trial of Injection of ex Vivo Amplified G-CSF Mobilised Autologous Peripheral Blood Stem Cell Transplantation in Adult Patients With Multiple Myeloma in First Response

Resource links provided by NLM:

MedlinePlus related topics: Multiple Myeloma

U.S. FDA Resources

Further study details as provided by University Hospital, Bordeaux:

Primary Outcome Measures:

Hematopoietic reconstitution defined by a neutrophils number > 500/mm3 at day 7 after injection of in vitro amplified graft and by a platelets number > 20000/mm3, at day 15 after the injection of in vitro amplified graft, without transfusion. [ Time Frame: at day 7 (neutrophils) and day 15 (platelets) after injection of in vitro amplified graft ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

Immediate Toxicity of the injection of the amplified graft ; [ Time Frame: just after the injection of the amplified graft ] [ Designated as safety issue: Yes ]
Quantitative immunological Reconstitution [ Time Frame: at day 30, 100, 180, 270, 360 after the injection and then every 6 months ] [ Designated as safety issue: Yes ]
Stability of the hematopoiesis in the long term [ Time Frame: at 1, 3, 6, 9 and 12 months after the graft ] [ Designated as safety issue: Yes ]
Absence of cytogenetics abnormalities not related to the multiple myeloma in the long term. [ Time Frame: at 1, 3, 6, 9 and 12 months after the injection ] [ Designated as safety issue: Yes ]

Estimated Enrollment:	13
Study Start Date:	August 2007
Study Completion Date:	August 2009
Primary Completion Date:	September 2008 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: 1 autologous peripheral blood stem cell transplantation	Procedure: autologous peripheral blood stem cell transplantation, ex vivo amplified autologous peripheral blood stem cell transplantation, ex vivo amplified

Detailed Description:

To check that injection of autologous peripheral blood stem cell CD34(+) "amplified ex vivo in the presence of SCF, G-CSF and TPO in HP01 Maco pharma medium culture. ": Allows to obtain a hematopoietic reconstitution:

Rapid : 7 days or less after the injection, regarding neutrophils and 15 days or less regarding platelets
Complete: numbers neutrophils and platelets respectively higher than 500/mm3 and 20000/mm3 within the times mentioned
Stable: no secondary neutropenia or thrombocytopenia during the year following the injection, in the absence of recurence of the myeloma.

Eligibility

Ages Eligible for Study:	18 Years to 65 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Patient between 18 and 65 years of age
Diagnosis of Multiple Myeloma, requiring a treatment, including high dose Melphalan whith autologous peripheral blood stem cell transplantation
Performance status: < 2 (Karnofsky > 70%)
Anticipated survival > 3 month
Collection of a minimum of 10x106 cells (CD34+)/Kg of autologous G-CSF mobilised peripheral blood stem cells in 2 to 3 pheresis.
Signed and dated informed consent

Exclusion Criteria:

Multiple Myeloma not requiring a treatment
Another cancer in the 5 years preceding the diagnosis or evolutive psychiatric affection
Positive serology for HIV, hepatitis C or hepatitis B
Hepato cellular insufficiency
Severe renal insufficiency defined by a creatine clearance < 30 ml/mn
Women pregnant or nursing, or effective absence of contraception
Antecedent of serious cardiac disease in the last 6 months.
Allergy known to the products derived from Escherichia Coli

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00461955

Locations

France
CHU Haut-Leveque
Pessac, France, 33604

Sponsors and Collaborators

University Hospital, Bordeaux

Investigators

Principal Investigator:

Noel MILPIED, MS, MD

University Hospital, Bordeaux

More Information

Publications:

Bernstein ID, Andrews RG, Zsebo KM. Recombinant human stem cell factor enhances the formation of colonies by CD34+ and CD34+lin- cells, and the generation of colony-forming cell progeny from CD34+lin- cells cultured with interleukin-3, granulocyte colony-stimulating factor, or granulocyte-macrophage colony-stimulating factor. Blood. 1991 Jun 1;77(11):2316-21.

Bodine DM, Crosier PS, Clark SC. Effects of hematopoietic growth factors on the survival of primitive stem cells in liquid suspension culture. Blood. 1991 Aug 15;78(4):914-20.

Boiron JM, Marit G, Faberes C, Cony-Makhoul P, Foures C, Ferrer AM, Cristol G, Sarrat A, Girault D, Reiffers J. Collection of peripheral blood stem cells in multiple myeloma following single high-dose cyclophosphamide with and without recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF). Bone Marrow Transplant. 1993 Jul;12(1):49-55.

Brandt J, Srour EF, van Besien K, Briddell RA, Hoffman R. Cytokine-dependent long-term culture of highly enriched precursors of hematopoietic progenitor cells from human bone marrow. J Clin Invest. 1990 Sep;86(3):932-41.

Brugger W, Heimfeld S, Berenson RJ, Mertelsmann R, Kanz L. Reconstitution of hematopoiesis after high-dose chemotherapy by autologous progenitor cells generated ex vivo. N Engl J Med. 1995 Aug 3;333(5):283-7. Retraction in: Kanz L, Brugger W. N Engl J Med. 2001 Jul 5;345(1):64.

Haylock DN, To LB, Dowse TL, Juttner CA, Simmons PJ. Ex vivo expansion and maturation of peripheral blood CD34+ cells into the myeloid lineage. Blood. 1992 Sep 15;80(6):1405-12.

Iscove NN, Shaw AR, Keller G. Net increase of pluripotential hematopoietic precursors in suspension culture in response to IL-1 and IL-3. J Immunol. 1989 Apr 1;142(7):2332-7.

Ivanovic Z, Duchez P, Dazey B, Hermitte F, Lamrissi-Garcia I, Mazurier F, Praloran V, Reiffers J, Vezon G, Boiron JM. A clinical-scale expansion of mobilized CD 34+ hematopoietic stem and progenitor cells by use of a new serum-free medium. Transfusion. 2006 Jan;46(1):126-31.

Kobayashi M, Imamura M, Gotohda Y, Maeda S, Iwasaki H, Sakurada K, Kasai M, Hapel AJ, Miyazaki T. Synergistic effects of interleukin-1 beta and interleukin-3 on the expansion of human hematopoietic progenitor cells in liquid cultures. Blood. 1991 Oct 15;78(8):1947-53.

Moore MA. Review: Stratton Lecture 1990. Clinical implications of positive and negative hematopoietic stem cell regulators. Blood. 1991 Jul 1;78(1):1-19. Review. No abstract available.

Moore MA. Hematopoietic reconstruction: new approaches. Clin Cancer Res. 1995 Jan;1(1):3-9. Review. No abstract available.

Muench MO, Moore MA. Accelerated recovery of peripheral blood cell counts in mice transplanted with in vitro cytokine-expanded hematopoietic progenitors. Exp Hematol. 1992 Jun;20(5):611-8.

Muench MO, Schneider JG, Moore MA. Interactions among colony-stimulating factors, IL-1 beta, IL-6, and kit-ligand in the regulation of primitive murine hematopoietic cells. Exp Hematol. 1992 Mar;20(3):339-49.

Reiffers J, Marit G, Vezon G, Cony-Makhoul P, Boiron JM, Montastruc M, Rice A, Broustet A. Autologous blood stem cell grafting in hematological malignancies. Present status and future directions. Transfus Sci. 1992;13(4):399-405. Review. No abstract available.

Reiffers J, Faberes C, Boiron JM, Marit G, Foures C, Ferrer AM, Cony-Makhoul P, Puntous M, Bernard P, Vezon G, et al. Peripheral blood progenitor cell transplantation in 118 patients with hematological malignancies: analysis of factors affecting the rate of engraftment. J Hematother. 1994 Fall;3(3):185-91.

Rice A, Boiron JM, Barbot C, Dupouy M, Dubsoc-Marchenay N, Dumain P, Lacombe F, Reiffers J. Cytokine-mediated expansion of 5-FU resistant peripheral blood stem cells and bone marrow: self-renewal and commitment capacity. J Hematother. 1994 Summer;3(2):135-9.

Shih JP, Ogawa M. Monoclonal antibody J11d.2 recognizes cell cycle-dormant, primitive hematopoietic progenitors of mice. Blood. 1993 Mar 1;81(5):1155-60.

Smith C, Gasparetto C, Collins N, Gillio A, Muench MO, O'Reilly RJ, Moore MA. Purification and partial characterization of a human hematopoietic precursor population. Blood. 1991 May 15;77(10):2122-8.

Responsible Party:	Jean-Pierre LEROY / Clinical Research and Innovation Director, University Hospital, Bordeaux
ClinicalTrials.gov Identifier:	NCT00461955 History of Changes
Other Study ID Numbers:	CHUBX 2000/04
Study First Received:	April 17, 2007
Last Updated:	November 3, 2010
Health Authority:	France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)

Keywords provided by University Hospital, Bordeaux:

Symptomatic Multiple Myeloma
first line treatment
first autologous Stem Cell Transplantation
ex vivo amplified autologous peripheral blood stem cells

Additional relevant MeSH terms:

Multiple Myeloma
Neoplasms, Plasma Cell
Neoplasms by Histologic Type
Neoplasms
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases

Paraproteinemias
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Lymphoproliferative Disorders
Immunoproliferative Disorders
Immune System Diseases

ClinicalTrials.gov processed this record on May 21, 2013

Injection of ex Vivo Amplified G-CSF Mobilised Autologous Peripheral Blood Stem Cell Transplantation (Expansion)