Clinical trial NCT01034449: Transplantation of Ex-vivo Expanded Cord Blood Stems Cells
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Malignant Haematological Disease
Keywords: allo graft
cord blood
expansion
reduced-intensity conditioning
Lead sponsor: University Hospital, Bordeaux
Sponsor class: OTHER
First posted: 2009-12-17
Enrollment: 16
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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 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

Primary outcomes:
measure: 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.
timeFrame: Daily for Blood évaluation and on days 15-42-60-100-180-360 for chimérisme évaluation.
Secondary outcomes:
measure: feasibility of expansion
timeFrame: during and after expansion
measure: 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.
timeFrame: during injection of the graft and within 3 hours of observation
measure: 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.
timeFrame: until the payback of the platelet count : measured daily during hospitalization and at least 2 times a week after
measure: The length of hospitalization since the beginning of conditioning until the first exit for more than 2 days.
timeFrame: lenght of hospitalization since the beginning of conditioning
measure: The number of transfusions of red blood cells and platelets during the 1st hospitalization
timeFrame: during the first hospitalization
measure: The incidence of graft loss or rejection within 6 months after transplantation, defined as the installation of a central cytopenia with loss of chimerism
timeFrame: Within 6 months after transplantation
measure: 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.
timeFrame: daily during hospitalization and at least twice weekly until D 100 after transplantation and then weekly or bi-monthly until one year post transplant.
measure: The mortality rate for transplantation in the year following the transplant,
timeFrame: in the year following the transplant
measure: The incidence of relapse of hematologic malignancies,
timeFrame: in the year following the transplant
measure: survival and disease-free survival in the year following the transplant
timeFrame: in the year following the transplant
measure: 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).
timeFrame: on days 15, 42, 60, 100, 180, 360
Other outcomes:
Locations:
city: Montpellier
country: France
facility: Service d'hématologie et d'Oncologie Clinique - Hôpital Lapeyronie - 371 avenue du Doyen Gaston GIRAUD
city: Nantes
country: France
facility: Service d'Hématologie, Hôpital Hôtel Dieu, CHU de Nantes - 1 Place Alexis Ricordeau
city: Pessac
country: France
facility: Service des maladies du sang - Hôpital Haut-Lévêque - avenue de Magellan
Study officials:
affiliation: University Hospital Bordeaux, France
name: Noel MILPIED, MD
role: PRINCIPAL_INVESTIGATOR
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