Efficacy of Heat-shock Protein (HSP) Inhibitors in Myeloproliferative Syndromes (MPS)

Myeloproliferative Syndrome Clinical Trial

— HSP-SMP  

Official title:

Efficacy of Heat-shock Protein (HSP) Inhibitors in Myeloproliferative Syndromes (MPS): Fundamental Observational in Vitro Study Using Samples From a Collection

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02873832
• Other study ID #: GIRODON 2014
• Status: Completed
• Phase: N/A
• First received: August 4, 2016
• Last updated: August 16, 2016
• Start date: January 2015

Study information

• Verified date: July 2016
• Source: Centre Hospitalier Universitaire Dijon
• Contact: n/a
• Is FDA regulated: No
• Health authority: France: Agence Nationale de Sécurité du Médicament et des produits de santé
• Study type: Observational

Clinical Trial Summary

Heat-shock proteins (HSP) have been very highly conserved throughout the evolution of species and are characterized by their chaperone function, thanks to their ability to prevent aggregation and to promote the renaturation/break down of damaged proteins. Among other targets, they also chaperone JAK2, a key step that is deregulated in signalling in myeloproliferative syndromes (MPS) because of the JAK2V617F mutation. These HSP also have a potent cytoprotective action through their multiples inhibiting effects on apoptotic processes.

Little is known about levels of HSP expression, in particular for HSP70 and HSP27, in MPS cells.

However, in vitro studies of different cell models have shown the interest of HSP90 inhibitors in slowing cell proliferation in MPS. These results have been confirmed in animal models with results in terms of blood counts and overall survival. In addition, it seems that the V617F mutated form of JAK2 is more sensitive than the wild-type to HSP90 inhibitors. Finally, inhibitors of HSP90 remain efficacious with regard to the inhibition of cell growth, even in cases of resistance to JAK2 inhibitors. Nonetheless, HSP90 inhibitors are known to stimulate the expression of other HSP, notably HSP27 and HSP70, which are, through their properties, tumorigenic and could lead to an escape phenomenon. Thus the combined use of several HSP inhibitors could be beneficial, and eventually present synergistic effects on the inhibition of tumour processes.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 37
• Est. primary completion date: April 2016
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

MPS Patients:

• Patients with MPS

• Patients who have been informed and not objected to the tests

• Patients over 18 years old

• Patients whose samples have been preserved at the CRB in the "Haemopathies" collection

Control patients:

• Patients over 18 years old

• Pregnant patients

• Patients who have been informed and not objected to the collection of their cord blood after the delivery

Exclusion Criteria:

• Adults under guardianship

Study Design

Time Perspective: Retrospective

Related Conditions & MeSH terms

• Myeloproliferative Disorders
• Myeloproliferative Syndrome
• Syndrome

Intervention

Biological:
• Blood sample

Other:
• Flow cytometry

• western blot

Locations

Country	Name	City	State
France	CHU Dijon Bourgogne	Dijon

Sponsors (1)

Lead Sponsor	Collaborator
Centre Hospitalier Universitaire Dijon

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Comparing the level of expression of HSP (HSP90, HSP70, HSP27) between cells from a collection of samples of patients with myeloproliferative disease and healthy controls .	Level of protein expression using flow cytometry and western blot	through study completion, an average of 1 year	No
Secondary	Cell death after in vitro treatment with different HSP inhibitors		through study completion, an average of 1 year	No