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

• ClinicalTrials.gov Identifier: NCT03119974
• Recruitment Status: Recruiting
• First Posted: April 19, 2017
• Last Update Posted: February 18, 2020
• Sponsor: Assistance Publique - Hôpitaux de Paris
• Information provided by (Responsible Party): Assistance Publique - Hôpitaux de Paris

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Persistent or Chronic ITP	Drug: Tpo-RA discontinuation	Phase 4

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 48 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Rate of Prolonged Response After Stopping Thrombopoietin-receptor Agonists Treatment in Immune Thrombocytopenia: a Prospective Multicenter Open Study
• Actual Study Start Date: April 18, 2017
• Estimated Primary Completion Date: April 2020
• Estimated Study Completion Date: April 2020

Arms and Interventions

Arm	Intervention/treatment
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.

Outcome Measures

Primary Outcome Measures :

1. 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 [ Time Frame: week 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 :

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

Eligibility Criteria

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

Criteria

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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Contacts and Locations

Contacts

Contact: Matthieu Mahevas, MD, PhD; (0)143812076 ext +33; matthieu.mahevas@aphp.fr

Locations

France

Henri-Mondor Hospital; Recruiting

Creteil, France, 94010

Sponsors and Collaborators

Assistance Publique - Hôpitaux de Paris

Investigators

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

More Information

• Responsible Party: Assistance Publique - Hôpitaux de Paris
• ClinicalTrials.gov Identifier: NCT03119974
• Other Study ID Numbers: P150956; 2016-001786-93 ( EudraCT Number )
• First Posted: April 19, 2017
• Last Update Posted: February 18, 2020
• Last Verified: February 2020

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Assistance Publique - Hôpitaux de Paris:

ITP; TPO-RAS; Thrombopoietin-receptor agonists