Rate of Prolonged Response After Stopping Thrombopoietin-receptor Agonists Treatment in ITP (STOP-AGO)

Rate of Prolonged Response After Stopping Thrombopoietin-receptor Agonists Treatment in Immune Thrombocytopenia: a Prospective Multicenter Open Study

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.

Study Overview

• Status: Unknown
• Conditions: Persistent or Chronic ITP
• Intervention / Treatment: Drug: Tpo-RA discontinuation

• Study Type: Interventional
• Enrollment (Anticipated): 48
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Matthieu Mahevas, MD, PhD; Phone Number: +33 (0)143812076; Email: matthieu.mahevas@aphp.fr

Study Locations

• France
  • Creteil, France, 94010
    • Recruiting
    • Henri-Mondor Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

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Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Tpo-RA discontinuation	Drug: Tpo-RA discontinuation; a standardized strategy of dosage reduction will be implemented according to a predetermined scheme on persistent and/or chronic ITP patients who have previously achieved a stable and prolonged (> 2 months) complete response (platelets counts > 100 x 109/L) period on Tpo-RA treatment.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 terminology	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:Their platelet count is < 30 x 109/L between week 0 and week 24, but also, in the setting of this study if:They need a rescue therapy (a new course of corticosteroids and/or intravenous immunoglobulin) after inclusion.	week 24 (6 months)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The rate of overall response after Tpo-RAs discontinuation	response and complete response	24 and 52 weeks
The duration of overall response after Tpo-RAs discontinuation.	response and complete response	24 and 52 weeks
The number of bleeding events during the reduction period and along the study period at weeks 4, 8, 12,24,36, 52	Safety assess of Tpo-RAs discontinuation	at weeks 4, 8, 12,24,36, 52
The rate of the response to a new course of Tpo-RAs in case of relapse after Tpo-RAs discontinuation at one year	Rate of the response in case of relapse	52 weeks
The delay of the response to a new course of Tpo-RAs in case of relapse after Tpo-RAs discontinuation	Delay of the response in case of relapse	52 weeks
To identify predictive factors, for overall prolonged response	Search for predictive factor of response	Weeks 24

Collaborators and Investigators

• Sponsor: Assistance Publique - Hôpitaux de Paris
• Investigators: Principal Investigator: Matthieu Mahevas, MD, PhD, Assistance Publique - Hôpitaux de Paris

Study record dates

Study Major Dates

• Study Start (Actual): April 18, 2017
• Primary Completion (Anticipated): April 1, 2020
• Study Completion (Anticipated): April 1, 2020

Study Registration Dates

• First Submitted: December 23, 2016
• First Submitted That Met QC Criteria: April 13, 2017
• First Posted (Actual): April 19, 2017

Study Record Updates

• Last Update Posted (Actual): February 18, 2020
• Last Update Submitted That Met QC Criteria: February 17, 2020
• Last Verified: February 1, 2020

More Information

Terms related to this study

• Keywords: ITP; TPO-RAS; Thrombopoietin-receptor agonists
• Other Study ID Numbers: P150956; 2016-001786-93 (EudraCT Number)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No