Transplantation of Ex-vivo Expanded Cord Blood Stems Cells

NCT01034449 | Completed Phase 2 DMC

• 1 other identifier: CHUBX 2008/12
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 3

Brief Summary

This program offers the opportunity to receive an allogeneic transplant to try to control the malignant hematologic in the absence of acceptable conventional donor and with a risk-benefit ratio equivalent to that which would be expected with a transplant from a more conventional donor. An economy of means in that this method could serve as an alternative to 2 units of placental blood transplantation. The current cost of disposal of a unit of placental blood from a bank is approximately 22000 € (Source: Biomedicine Agency, 2007 rates). The amplification process as controlled by "EFSAL" is 12000 €. Therefore, buying a unit and ex-vivo amplification is more economical. Moreover, the availability of placental blood is not infinite, and the use of one unit per patient will also save resources that can be valuable for certain groups of patients. In the longer term, methods of amplification of specific immunocompetent cells (from the fraction of CD 34 neg cells) are already being evaluated in the laboratory. They allow to consider a faster recovery, better and more targeted, including cells against the disease for which transplantation is performed.

Conditions

Malignant Haematological Disease

Keywords

allo graft; cord blood; expansion; reduced-intensity conditioning

Outcome Measures

Primary Outcomes (1)

• The number of granulocytes, which will be evaluated daily after transplantation. And chimerism to be measured on the cells (total nucleated cells and lymphocytes) from peripheral blood on days 15, 42, 60, 100, 180, 360.

  Daily for Blood évaluation and on days 15-42-60-100-180-360 for chimérisme évaluation.

Secondary Outcomes (11)

• feasibility of expansion

  during and after expansion

• Immediate tolerance of a graft amplified injection. Determined by measurement of vital parameters during injection of the graft and within 3 hours of observation and clinical tolerance.

  during injection of the graft and within 3 hours of observation

• The payback of a platelet count> 20 000/microlitre bloodless. Measured by the blood count and platelet daily during hospitalization and at least 2 times a week.

  until the payback of the platelet count : measured daily during hospitalization and at least 2 times a week after

• The length of hospitalization since the beginning of conditioning until the first exit for more than 2 days.

  lenght of hospitalization since the beginning of conditioning

• The number of transfusions of red blood cells and platelets during the 1st hospitalization

  during the first hospitalization

Interventions

allogeneic transplant OTHER

ex vivo amplification of a unit of placental blood for transplantation

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥ 18 and \< 66 years
• Patient with acute myeloid leukemia (AML) high risk in 1st complete remission:
• CR1 obtained by 2 cycles of chemotherapy,
• unfavorable Cytogenetics
• FLT3 Duplication,
• Or acute myeloid leukemia (AML) in 2nd complete remission,
• Or acute lymphoblastic leukemia (ALL) High-risk 1st complete remission:
• Presence of the translocation t (9; 22),
• Or acute lymphoblastic leukemia (ALL) in 2nd complete remission,
• Or Chronic Myeloid Leukemia (LCM) beyond the 1st chronic phase
• Or Myelodysplasia or with IPSS score with 2 or more
• Or Hodgkin's disease in sensitive relapse or beyond the 2nd complete remission. or following types of lymphoma :
• Diffuse large B lymphoma cells relapsed or refractory after two lines of treatment or after a line with autologous hematopoietic stem cell, or
• Mantle cell lymphoma relapsed or refractory after two lines of treatment or after a line with autologous hematopoietic stem cell
• Others aggressive lymphoma for which an indication of allograft is selected (Burkitt lymphoma, lymphoblastic lymphoma, intravascular lymphoma, ...)

You may not qualify if:

• Age \<18 and ≥ 66 years
• Malignant myeloid or lymphoid acute or chronic disease without indication for an allogeneic transplant according to the criteria of European Bone Marrow Transplantation Group.
• Able to receive a myeloablative conditioning because of age (\<45 years) and the absence of co morbidities (status ECOG\> / = 2, DLCO \<50%, fungal infection proven or probable in 60 preceding days) and the absence of prior treatment with total body irradiation at doses above 2 Gy or busulfan doses\> 8 mg / kg
• Contra indication for a non-myeloablative conditioning,
• HLA-identical sibling available
• Availability of an unrelated donor on a national or international register with 10/10 or 9/10 HLA matching (HLA-C Mismatch tolerated).
• At least one unit of cord blood available with the characteristics of compatibility (HLA compatible at least 4/6 allelic or generic) and richness (before thawing\> / = 3 to 4 x 107 nucleated cells/kg recipient, by degree of compatibility)
• Absence of at least 2 units of placental blood, whose compatibility is 4/6, 5/6 / or 6/6 and whose richness before thawing is \> 2 x 107 and \< 4 x 107 nucleated cells per/kg of recipient.
• Women of childbearing age not using contraception, pregnant or lactating

Sponsors & Collaborators

• University Hospital, Bordeaux: lead

Study Sites (3)

Service d'hématologie et d'Oncologie Clinique - Hôpital Lapeyronie - 371 avenue du Doyen Gaston GIRAUD

Montpellier, 34295, France

Location

Service d'Hématologie, Hôpital Hôtel Dieu, CHU de Nantes - 1 Place Alexis Ricordeau

Nantes, 44093, France

Location

Service des maladies du sang - Hôpital Haut-Lévêque - avenue de Magellan

Pessac, 33600, France

Location

Related Publications (15)

• Petersdorf EW. Risk assessment in haematopoietic stem cell transplantation: histocompatibility. Best Pract Res Clin Haematol. 2007 Jun;20(2):155-70. doi: 10.1016/j.beha.2006.09.001.

  PMID: 17448954 BACKGROUND

• Koh LP, Chao NJ. Umbilical cord blood transplantation in adults using myeloablative and nonmyeloablative preparative regimens. Biol Blood Marrow Transplant. 2004 Jan;10(1):1-22. doi: 10.1016/j.bbmt.2003.09.009.

  PMID: 14752775 BACKGROUND

• Barker JN, Weisdorf DJ, DeFor TE, Blazar BR, McGlave PB, Miller JS, Verfaillie CM, Wagner JE. Transplantation of 2 partially HLA-matched umbilical cord blood units to enhance engraftment in adults with hematologic malignancy. Blood. 2005 Feb 1;105(3):1343-7. doi: 10.1182/blood-2004-07-2717. Epub 2004 Oct 5.

  PMID: 15466923 BACKGROUND

• Castello S, Podesta M, Menditto VG, Ibatici A, Pitto A, Figari O, Scarpati D, Magrassi L, Bacigalupo A, Piaggio G, Frassoni F. Intra-bone marrow injection of bone marrow and cord blood cells: an alternative way of transplantation associated with a higher seeding efficiency. Exp Hematol. 2004 Aug;32(8):782-7. doi: 10.1016/j.exphem.2004.05.026.

  PMID: 15308330 BACKGROUND

• Shpall EJ, Quinones R, Giller R, Zeng C, Baron AE, Jones RB, Bearman SI, Nieto Y, Freed B, Madinger N, Hogan CJ, Slat-Vasquez V, Russell P, Blunk B, Schissel D, Hild E, Malcolm J, Ward W, McNiece IK. Transplantation of ex vivo expanded cord blood. Biol Blood Marrow Transplant. 2002;8(7):368-76. doi: 10.1053/bbmt.2002.v8.pm12171483.

  PMID: 12171483 BACKGROUND

• Ljungman P, Urbano-Ispizua A, Cavazzana-Calvo M, Demirer T, Dini G, Einsele H, Gratwohl A, Madrigal A, Niederwieser D, Passweg J, Rocha V, Saccardi R, Schouten H, Schmitz N, Socie G, Sureda A, Apperley J; European Group for Blood and Marrow. Allogeneic and autologous transplantation for haematological diseases, solid tumours and immune disorders: definitions and current practice in Europe. Bone Marrow Transplant. 2006 Mar;37(5):439-49. doi: 10.1038/sj.bmt.1705265.

  PMID: 16444286 BACKGROUND

• Brunstein CG, Barker JN, Weisdorf DJ, DeFor TE, Miller JS, Blazar BR, McGlave PB, Wagner JE. Umbilical cord blood transplantation after nonmyeloablative conditioning: impact on transplantation outcomes in 110 adults with hematologic disease. Blood. 2007 Oct 15;110(8):3064-70. doi: 10.1182/blood-2007-04-067215. Epub 2007 Jun 14.

  PMID: 17569820 BACKGROUND

• Gluckman E, Rocha V. Donor selection for unrelated cord blood transplants. Curr Opin Immunol. 2006 Oct;18(5):565-70. doi: 10.1016/j.coi.2006.07.014. Epub 2006 Aug 8.

  PMID: 16893632 BACKGROUND

• Takahashi S. Leukemia: cord blood for allogeneic stem cell transplantation. Curr Opin Oncol. 2007 Nov;19(6):667-72. doi: 10.1097/CCO.0b013e3282f0e1a1.

  PMID: 17906469 BACKGROUND

• Kobari L, Pflumio F, Giarratana M, Li X, Titeux M, Izac B, Leteurtre F, Coulombel L, Douay L. In vitro and in vivo evidence for the long-term multilineage (myeloid, B, NK, and T) reconstitution capacity of ex vivo expanded human CD34(+) cord blood cells. Exp Hematol. 2000 Dec;28(12):1470-80. doi: 10.1016/s0301-472x(00)00557-9.

  PMID: 11146169 BACKGROUND

• Duchez P, Dazey B, Douay L, Vezon G, Ivanovic Z. An efficient large-scale thawing procedure for cord blood cells destined for selection and ex vivo expansion of CD34+ cells. J Hematother Stem Cell Res. 2003 Oct;12(5):587-9. doi: 10.1089/152581603322448295. No abstract available.

  PMID: 14594515 BACKGROUND

• Dazey B, Duchez P, Letellier C, Vezon G, Ivanovic Z; French Cord Blood Network. Cord blood processing by using a standard manual technique and automated closed system "Sepax" (Kit CS-530). Stem Cells Dev. 2005 Feb;14(1):6-10. doi: 10.1089/scd.2005.14.6. No abstract available.

  PMID: 15725739 BACKGROUND

• 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. doi: 10.1111/j.1537-2995.2005.00675.x.

  PMID: 16398741 BACKGROUND

• Barker JN, Weisdorf DJ, DeFor TE, Blazar BR, Miller JS, Wagner JE. Rapid and complete donor chimerism in adult recipients of unrelated donor umbilical cord blood transplantation after reduced-intensity conditioning. Blood. 2003 Sep 1;102(5):1915-9. doi: 10.1182/blood-2002-11-3337. Epub 2003 May 8.

  PMID: 12738676 BACKGROUND

• Ljungman P, Bregni M, Brune M, Cornelissen J, de Witte T, Dini G, Einsele H, Gaspar HB, Gratwohl A, Passweg J, Peters C, Rocha V, Saccardi R, Schouten H, Sureda A, Tichelli A, Velardi A, Niederwieser D; European Group for Blood and Marrow Transplantation. Allogeneic and autologous transplantation for haematological diseases, solid tumours and immune disorders: current practice in Europe 2009. Bone Marrow Transplant. 2010 Feb;45(2):219-34. doi: 10.1038/bmt.2009.141. Epub 2009 Jul 6.

  PMID: 19584824 BACKGROUND

MeSH Terms

Interventions

Transplantation, Homologous

Intervention Hierarchy (Ancestors)

Transplantation; Surgical Procedures, Operative

Study Officials

• Noel MILPIED, MD

  University Hospital Bordeaux, France

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 16, 2009
• First Posted: December 17, 2009
• Study Start: February 1, 2010
• Primary Completion: October 1, 2013
• Study Completion: September 1, 2014
• Last Updated: January 13, 2015

Record last verified: 2015-01

Locations

FR (3)