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Rate of Prolonged Response After Stopping Thrombopoietin-receptor Agonists Treatment in ITP

Phase 4
Conditions
Persistent or Chronic ITP
Interventions
Drug: Tpo-RA discontinuation
Registration Number
NCT03119974
Lead Sponsor
Assistance Publique - Hôpitaux de Paris
Brief Summary

Thrombopoietin-receptor agonists (Tpo-RAs) have profoundly changed the management of ITP. However, today, there are no international recommendations concerning the long-term use of these costly, potentially pro-thrombotic agents, and that could induce bone marrow fibrosis in case of prolonged treatment. Tpo-RAs have been thought to play only a supporting role in ITP management. But our center along with many other research centers, have reported unexpected cases of durable remission after Tpo-RAs discontinuation in adult chronic ITP. In these retrospective studies, more than 20 % of patients were able to achieve prolonged remission.

The purpose of this study is to demonstrate that a substantial proportion of ITP patients may achieve a prolonged response after Tpo-RA discontinuation.

The investigators developed, in this study, a standardized procedure to discontinue Eltrombopag and Romiplostim, wherein the dose will be slowly tapered to limit the risk of bleeding. In case of relapse after Tpo-RA discontinuation, the decision to start a new therapy will be based on the clinician's judgment.

Detailed Description

Not available

Recruitment & Eligibility

Status
UNKNOWN
Sex
All
Target Recruitment
48
Inclusion Criteria
  1. Age >= 18 years
  2. Diagnosis of ITP according to the standard definition
  3. Disease duration of more than 3 months at Tpo-RA initiation
  4. Platelet count > 100 x 109/L for more than 2 months on Tpo-RA Therapy, with at least 3 platelet counts > 100 x 109/L
  5. Blood count lasting for less than 7 days
  6. Normal marrow aspirate for patients aged of 60 and over
  7. Informed signed consent
  8. Treatment with Tpo-RA for at least 3 months
Exclusion Criteria
  1. Anticoagulation or anti-platelet treatment 2) Recent treatment with corticosteroids ± intravenous immunoglobulins (less than 2 months) 3) Rituximab or splenectomy within the 2 months preceding the Tpo-RA initiation 4) Rituximab or splenectomy after Tpo-RA initiation/RA initiation 5) Previous failure of Tpo-RA discontinuation 6) Pregnant or breastfeeding women 7) No affiliation to a social security scheme or other social protection scheme 8) Inability or refusal to understand or refusal to sign the informed consent from study participation 9) Patient deprived of freedom or under legal protection (guardianship, curatorship) 10) Hypersensitivity to Romiplostin or to any of the excipients or to E. coli derived proteins

Study & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
Tpo-RA discontinuationTpo-RA discontinuation-
Primary Outcome Measures
NameTimeMethod
The proportion of patients achieving an overall response (complete response and response) at week 24 (6 months). The criteria of response will be defined according to international terminologyweek 24 (6 months)

the criteria of response will be defined as the following:

* Response (R) will be defined as sustained platelet count \>30x109/L in the absence of bleeding or use of any other ITP directed therapies between the week 0 (discontinuation) and week 24.

* Complete response (CR) by a platelet count \> 100x 109/L in the absence use of any other ITP directed therapies between week 0 and week 24.

* Patients will be considered as being non-responders (NR) if:

1. Their platelet count is \< 30 x 109/L between week 0 and week 24, but also, in the setting of this study if:

2. They need a rescue therapy (a new course of corticosteroids and/or intravenous immunoglobulin) after inclusion.

Secondary Outcome Measures
NameTimeMethod
The rate of overall response after Tpo-RAs discontinuation24 and 52 weeks

response and complete response

The duration of overall response after Tpo-RAs discontinuation.24 and 52 weeks

response and complete response

The number of bleeding events during the reduction period and along the study period at weeks 4, 8, 12,24,36, 52at weeks 4, 8, 12,24,36, 52

Safety assess of Tpo-RAs discontinuation

The rate of the response to a new course of Tpo-RAs in case of relapse after Tpo-RAs discontinuation at one year52 weeks

Rate of the response in case of relapse

The delay of the response to a new course of Tpo-RAs in case of relapse after Tpo-RAs discontinuation52 weeks

Delay of the response in case of relapse

To identify predictive factors, for overall prolonged responseWeeks 24

Search for predictive factor of response

Trial Locations

Locations (1)

Henri-Mondor Hospital

🇫🇷

Creteil, France

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