Informations générales (source: ClinicalTrials.gov)
Evaluation of the Effectiveness of an Aldehyde Inhibitor Dehydrogenases (DIMATE) on the Cell Population Leukemic or Normal Stem (DIMATE)
Interventional
N/A
Assistance Publique Hopitaux De Marseille (Voir sur ClinicalTrials)
juin 2016
juin 2022
29 juin 2024
Aldehyde dehydrogenases (ALDHs) are cellular enzymes responsible for detoxifying aldehyde
resulting from the metabolism of endogenous and exogenous xenobiotic cellular
constituents. Although ALDHs are considered to play an important role in tumorigenesis,
the role of ALDH activity in cancer stem cells, and more particularly that of the acute
leukemia must be specified.
Several studies have shown that ALDHs are potent apoptogenic compounds on normal or
cancer cells. Therefore, the cells that were damaged and their increased ALDH activity
does not die by apoptosis but become highly proliferating. This result is a plausible
mechanism for the "evasion of apoptosis", a characteristic shared by many cancer cells.
On this basis, it is proposed an innovative approach to cancer chemotherapy through
inhibition of one of the protective mechanisms against apoptosis, ie the increase in ALDH
activity than cancer cells put involved in overcoming the lethal effects of damaged
roads. ALDHs of inhibitors they may have immediate application as anti -cancer in vivo?
The limited experimental data obtained so far on human tumor xenografts in
immunodeficient mice and the absence of data on the in vivo toxicology do not allow
direct passage to clinical trials. Indeed, some members of the ALDH superfamily are
expressed constitutively in some vital organs they protect against the deleterious
effects of xenobiotics and adverse endogenous metabolites. Consequently, if ALDHs should
be inhibited, of the collateral damages for the normal cells could occur. However, when
normal cells have not undergone deleterious exposure, these harmful metabolites are not
or in very small quantities, which do not require high levels of ALDH activity, and
therefore without harm to the inhibition of cell of these enzymes.
From a hematological point of view, it seems essential to test the therapeutic index of
the inhibitor of ALDH DIMATE between normal hematopoietic cells and leukemic stem.
Indeed, in the pathophysiology of acute leukemia, the leukemia stem cells are of major
importance because they are much more resistant to chemotherapy than more differentiated
cells and thus causing the high rate of relapse observed in acute leukemia despite the
high rate of complete remission often obtained. In this study, it will be tested in vitro
sensitivity of the cluster of differentiation 4 and cluster of differentiation 38
(CD4/CD38) highly purified of leukemic origin or normal to the DIMATE compound. The
objective will be to analyze the effects of DIMATE on the parameters of the
proliferation, the apoptose, the cytokinins of secretions and the changes transcriptomic
in general, in order to better define the therapeutic index of this compound and to
determine all the precursory hematopoietic normals and leukaemic cellular effects. The
reversible cytostatic of DIMATE effect on normal cells but its irreversible apoptotic
effect on cancer cells is an advantage to try to eliminate.
Etablissements
| Les établissements hors Île-de-France dont les données sont issues de ClinicalTrials.gov Origine et niveau de fiabilité des données | |||||
|---|---|---|---|---|---|
| Assistance Publique Hôpitaux de Marseille - 13354 - Marseille - France | Emilie GARRIDO-PRADALIE, Director | Contact (sur clinicalTrials) | |||
Critères
Tous
Inclusion Criteria:
- Subject, man or woman, whose age is above 18 years
- Subject whose physical and mental condition allows him to understand the information
leaflet
- Presenting acute leukemia and / or refractory anemia with excess blasts and blasts
with a higher peripheral blood 5%. For leukemic Group
- Subject to benefit from apheresis for autologous stem cell transplantation as part
of a non-myeloid hematological malignancy. For the Group Cytapheresis
- Subject affiliated to the social security scheme
- Subject has signed an informed consent
- Subject with a medical examination adapted to the study was conducted
- Subject, man or woman, whose age is above 18 years
- Subject whose physical and mental condition allows him to understand the information
leaflet
- Presenting acute leukemia and / or refractory anemia with excess blasts and blasts
with a higher peripheral blood 5%. For leukemic Group
- Subject to benefit from apheresis for autologous stem cell transplantation as part
of a non-myeloid hematological malignancy. For the Group Cytapheresis
- Subject affiliated to the social security scheme
- Subject has signed an informed consent
- Subject with a medical examination adapted to the study was conducted
- Subject, man or woman, whose age is above 18 years
- Subject previously treated with chemotherapy for his leukemia. For leukemic Group
- Subject considered "vulnerable person" (Major deprived of freedom, under
guardianship, pregnant and lactating women and minors)
- Subject refusing to participate in the study
- Subject not having signed an informed consent