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

January 12, 2015 updated by: University Hospital, Bordeaux

Transplantation of Ex-vivo Expanded Human Cord Blood Hematopoietic Stem Cells Expanded: Evaluation of Hematopoietic and Immunologic Reconstitution After a Reduced-intensity Conditioning Regimen

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

16

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • France
      • Montpellier, France, 34295
        • Service d'hématologie et d'Oncologie Clinique - Hôpital Lapeyronie - 371 avenue du Doyen Gaston GIRAUD
      • Nantes, France, 44093
        • Service d'Hématologie, Hôpital Hôtel Dieu, CHU de Nantes - 1 Place Alexis Ricordeau
      • Pessac, France, 33600
        • Service des maladies du sang - Hôpital Haut-Lévêque - avenue de magellan

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 65 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure
Time Frame
feasibility of expansion
Time Frame: during and after 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.
Time Frame: during injection of the graft and within 3 hours of observation
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.
Time Frame: until the payback of the platelet count : measured daily during hospitalization and at least 2 times a week after
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.
Time Frame: lenght of hospitalization since the beginning of conditioning
lenght of hospitalization since the beginning of conditioning
The number of transfusions of red blood cells and platelets during the 1st hospitalization
Time Frame: during the first hospitalization
during the first hospitalization
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
Within 6 months after transplantation
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.
daily during hospitalization and at least twice weekly until D 100 after transplantation and then weekly or bi-monthly until one year post transplant.
The mortality rate for transplantation in the year following the transplant,
Time Frame: in the year following the transplant
in the year following the transplant
The incidence of relapse of hematologic malignancies,
Time Frame: in the year following the transplant
in the year following the transplant
survival and disease-free survival in the year following the transplant
Time Frame: in the year following the transplant
in the year following the transplant
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
on days 15, 42, 60, 100, 180, 360

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University Hospital, Bordeaux

Investigators

  • Principal Investigator: Noel MILPIED, MD, University Hospital Bordeaux, France

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

February 1, 2010

Primary Completion (Actual)

October 1, 2013

Study Completion (Actual)

September 1, 2014

Study Registration Dates

First Submitted

December 16, 2009

First Submitted That Met QC Criteria

December 16, 2009

First Posted (Estimate)

December 17, 2009

Study Record Updates

Last Update Posted (Estimate)

January 13, 2015

Last Update Submitted That Met QC Criteria

January 12, 2015

Last Verified

January 1, 2015

More Information

Terms related to this study

Keywords

Other Study ID Numbers

  • CHUBX 2008/12

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Malignant Haematological Disease

Clinical Trials on allogeneic transplant

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Zambia

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

Subscribe