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

Multiple Myeloma Clinical Trial

— Expansion  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00461955
• Other study ID #: CHUBX 2000/04
• Status: Completed
• Phase: Phase 2
• First received: April 17, 2007
• Last updated: November 3, 2010
• Start date: August 2007
• Est. completion date: August 2009

Study information

• Verified date: November 2010
• Source: University Hospital, Bordeaux
• Contact: n/a
• Is FDA regulated: No
• Health authority: France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
• Study type: Interventional

Clinical Trial Summary

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.

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:

1. Rapid : 7 days or less after the injection, regarding neutrophils and 15 days or less regarding platelets

2. Complete: numbers neutrophils and platelets respectively higher than 500/mm3 and 20000/mm3 within the times mentioned

3. Stable: no secondary neutropenia or thrombocytopenia during the year following the injection, in the absence of recurence of the myeloma.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 13
• Est. completion date: August 2009
• Est. primary completion date: September 2008
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 65 Years

Eligibility

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

Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Multiple Myeloma
• Neoplasms, Plasma Cell

Intervention

Procedure:
• autologous peripheral blood stem cell transplantation, ex vivo amplified
autologous peripheral blood stem cell transplantation, ex vivo amplified

Locations

Country	Name	City	State
France	CHU Haut-Leveque	Pessac

Sponsors (1)

Lead Sponsor	Collaborator
University Hospital, Bordeaux

Country where clinical trial is conducted

France, 

References & Publications (18)

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. — View Citation

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. — View Citation

Boiron JM, Marit G, Fabéres 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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

Moore MA. Hematopoietic reconstruction: new approaches. Clin Cancer Res. 1995 Jan;1(1):3-9. Review. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

* Note: There are 18 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.		at day 7 (neutrophils) and day 15 (platelets) after injection of in vitro amplified graft	Yes
Secondary	Immediate Toxicity of the injection of the amplified graft ;		just after the injection of the amplified graft	Yes
Secondary	Quantitative immunological Reconstitution		at day 30, 100, 180, 270, 360 after the injection and then every 6 months	Yes
Secondary	Stability of the hematopoiesis in the long term		at 1, 3, 6, 9 and 12 months after the graft	Yes
Secondary	Absence of cytogenetics abnormalities not related to the multiple myeloma in the long term.		at 1, 3, 6, 9 and 12 months after the injection	Yes