Transplantation of Ex-vivo Expanded Cord Blood Stems Cells (GRAPA)

This study is currently recruiting participants. (see Contacts and Locations)
Verified April 2014 by University Hospital, Bordeaux
Sponsor:
Information provided by (Responsible Party):
University Hospital, Bordeaux
ClinicalTrials.gov Identifier:
NCT01034449
First received: December 16, 2009
Last updated: April 1, 2014
Last verified: April 2014
  Purpose

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.


Condition Intervention Phase
Malignant Haematological Disease
Other: allogeneic transplant
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Transplantation of Ex-vivo Expanded Human Cord Blood Hematopoietic Stem Cells Expanded: Evaluation of Hematopoietic and Immunologic Reconstitution After a Reduced-intensity Conditioning Regimen

Resource links provided by NLM:


Further study details as provided by University Hospital, Bordeaux:

Primary Outcome Measures:
  • 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. [ Time Frame: Daily for Blood évaluation and on days 15-42-60-100-180-360 for chimérisme évaluation. ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • feasibility of expansion [ Time Frame: during and after expansion ] [ Designated as safety issue: No ]
  • 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. [ Time Frame: during injection of the graft and within 3 hours of observation ] [ Designated as safety issue: Yes ]
  • 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. [ Time Frame: until the payback of the platelet count : measured daily during hospitalization and at least 2 times a week after ] [ Designated as safety issue: Yes ]
  • The length of hospitalization since the beginning of conditioning until the first exit for more than 2 days. [ Time Frame: lenght of hospitalization since the beginning of conditioning ] [ Designated as safety issue: No ]
  • The number of transfusions of red blood cells and platelets during the 1st hospitalization [ Time Frame: during the first hospitalization ] [ Designated as safety issue: No ]
  • The incidence of graft loss or rejection within 6 months after transplantation, defined as the installation of a central cytopenia with loss of chimerism [ Time Frame: Within 6 months after transplantation ] [ Designated as safety issue: Yes ]
  • The incidence of acute and chronic GVHD,determined by clinical examination Biopsies of target organs(skin, intestine, liver) will be conducted to confirm the diagnosis if possible. [ Time Frame: daily during hospitalization and at least twice weekly until D 100 after transplantation and then weekly or bi-monthly until one year post transplant. ] [ Designated as safety issue: Yes ]
  • The mortality rate for transplantation in the year following the transplant, [ Time Frame: in the year following the transplant ] [ Designated as safety issue: Yes ]
  • The incidence of relapse of hematologic malignancies, [ Time Frame: in the year following the transplant ] [ Designated as safety issue: Yes ]
  • survival and disease-free survival in the year following the transplant [ Time Frame: in the year following the transplant ] [ Designated as safety issue: Yes ]
  • Monitoring of immune reconstitution. This reconstruction will be followed by determining the rate of immunoglobulin G, M and A and the number of T lymphocytes CD3 +, CD4 + and CD8 + (assessments on days 15, 42, 60, 100, 180, 360). [ Time Frame: on days 15, 42, 60, 100, 180, 360 ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 15
Study Start Date: February 2010
Estimated Study Completion Date: May 2015
Estimated Primary Completion Date: August 2014 (Final data collection date for primary outcome measure)
Intervention Details:
    Other: allogeneic transplant
    ex vivo amplification of a unit of placental blood for transplantation
Detailed Description:

This is a multicenter prospective non randomized phase 2 clinical trial.

The primary objective is defined by getting a neutrophil count above 500/ml for 3 consecutive days at day 42 after transplantation, in association with complete or partial chimerism on T cells (10 % to 90%).

The secondary objectives are:

  • the feasibility of expansion,
  • tolerance immediate injection of a graft amplified,
  • the payback of a platelet count> 20 000/microlitre without transfusion,
  • Incidence of graft loss or rejection within 6 months following transplantation,
  • the incidence of acute and chronic GVHD,
  • the mortality rate associated with transplantation,
  • the incidence of relapse of hematologic malignancies,
  • Overall survival,
  • Disease-free survival at 1 year post transplant.
  Eligibility

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

Inclusion Criteria:

  • 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, ...)
  • Lymphoma (low-grade follicular lymphoma, marginal zone lymphoma) in histological transformation.
  • Low-grade lymphoma for which an indication of allograft is retained
  • Unable to receive myeloablative conditioning because of age (> 45 years) and/or the existence of co-morbidities precluding a myeloablative conditioning (status ECOG > / = 2, DLCO <50%, fungal infection proven or probable in the previous 60 days) and / or prior treatment with total body irradiation at doses above 2 Gy or busulfan doses> 8 mg/kg
  • No contra-indication for a transplant in allogeneic non-myeloablative conditioning,
  • No HLA-identical sibling,
  • Absence of an unrelated donor on national or international registering with a 10/10 allelic matching or a 9/10 allelic matching with the only tolerated mismatches being: HLA-C.
  • No unit of placental blood available fulfilling the characteristics of compatibility (HLA compatible at least 4/6 allele or generic) and richness
  • Provision of at least 2 units of placental blood, whose compatibility is 4/6, 5/6 or 6/6 and whose richness is before thawing, > 2 x 107 and < 3 to 4 x 107 nucleated cells per/kg.
  • Patient affiliated to a social security scheme,
  • Free and informed consent signed by the patient and the investigator.

Exclusion Criteria:

  • 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01034449

Contacts
Contact: Noel MILPIED, MD 33(0)5 57 65 65 11 noel.milpied@chu-bordeaux.fr

Locations
France
Service d'hématologie et d'Oncologie Clinique - Hôpital Lapeyronie - 371 avenue du Doyen Gaston GIRAUD Not yet recruiting
Montpellier, France, 34295
Principal Investigator: Jean-François ROSSI         
Sub-Investigator: Patrice CEBALLOS         
Sub-Investigator: Nathalie FEGUEUX         
Sub-Investigator: Jean Côme MENIANE         
Service d'Hématologie, Hôpital Hôtel Dieu, CHU de Nantes - 1 Place Alexis Ricordeau Recruiting
Nantes, France, 44093
Principal Investigator: Mohamad MOHTY         
Sub-Investigator: Thierry GUILLAUME         
Sub-Investigator: Jacques DELAUNAY         
Sub-Investigator: Patrice CHEVALLIER         
Service des maladies du sang - Hôpital Haut-Lévêque - avenue de Magellan Recruiting
Pessac, France, 33600
Contact: Noel MILPIED       noel.milpied@chu-bordeaux.fr   
Sub-Investigator: Reza TABRIZI         
Sub-Investigator: Stephane VIGOUROUX         
Sub-Investigator: Arnaud PIGNEUX         
Sub-Investigator: Krimo BOUABDALLAH         
Sub-Investigator: Marie-Sarah DILHUYDY         
Sub-Investigator: Thibaut LEGUAY         
Sub-Investigator: Carine FOUCAUD         
Principal Investigator: Noel MILPIED         
Sponsors and Collaborators
University Hospital, Bordeaux
Investigators
Principal Investigator: Noel MILPIED, MD University Hospital Bordeaux, France
  More Information

Publications:

Responsible Party: University Hospital, Bordeaux
ClinicalTrials.gov Identifier: NCT01034449     History of Changes
Other Study ID Numbers: CHUBX 2008/12
Study First Received: December 16, 2009
Last Updated: April 1, 2014
Health Authority: France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)

Keywords provided by University Hospital, Bordeaux:
allo graft
cord blood
expansion
reduced-intensity conditioning

Additional relevant MeSH terms:
Hematologic Diseases

ClinicalTrials.gov processed this record on August 26, 2014