Clinical trial NCT04812483: Immunomodulation With Eltrombopag in ITP
Official title: Immunomodulation in Young and Midlife Adults With Newly Diagnosed Primary Immune Thrombocytopenia (ITP): A Randomized Open Label Trial With High-dose Dexamethasone Versus Eltrombopag and High-dose Dexamethasone
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Primary Immune Thrombocytopenia (ITP)
Keywords: eltrombopag
thrombopoietin receptor agonist (TPO-RA)
ITP in young and midlife adults
Lead sponsor: University Children's Hospital Basel
Sponsor class: OTHER
Collaborators: name: Stiftung zur Förderung medizinischer und biologischer Forschung
name: Novartis Pharmaceuticals
name: University of Erlangen-Nürnberg, Department of Biology
First posted: 2021-03-23
Enrollment: 2
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Randomized study evaluating the immunomodulatory effects of eltrombopag versus standard high-dose (HD) DXM therapy (1:1) in newly diagnosed ITP.
Primary purpose: TREATMENT

Brief summary: The study aims to investigate immunomodulatory effects of eltrombopag combined with dexamethasone in young and midlife adult patients with newly diagnosed primary Immune thrombocytopenia (ITP).

Detailed description: The randomized open lable study aims to investigate immunomodulatory effects of eltrombopag combined with dexamethasone in young and midlife adult patients with newly diagnosed primary ITP. Treatment protocol will be HD-DXM (40 mg PO, day 1-4) with or without eltrombopag (25-50 mg PO, day 5-140) on an outpatient basis. Immunological investigations will be performed before start of treatment and then on week 3, 20 (end of therapy) and 30.

1. Intervention phase:

   Medical history and physical examination including assessment of severe bleeding every week until week 4, every second week until week 20. Complete blood count every week until week 10. For the adjustment of the Thrombopoietin receptor agonist (TPO-RA) dose - every second week until week 20. Immunologic panel at the beginning and at week 3 and 20.
2. Follow-up:

Three clinical visits are scheduled in the follow-up including a complete blood count: at week 22, 24 and 30. Immunologic panel will be done at week 30 (end of study).

High-dose dexamethasone (HD-DXM) will be administered orally (40 mg) from day 1-4, followed by Arm 1 or 2 (1:1 randomization).

Arm 1: Standard Arm No planed further treatment. = standard therapy. In case of non-response after 2 courses of HD-DXM (week 4): cross-over to Arm 2: Start Eltrombopag (Revolade®), 50 mg PO until day 140 (details see Arm 2).

In case of relapse: repeat HD-DXM (40 mg day 1-4), up to a maximal of 3 courses. Time between 2 courses should be minimal 14 days. In case of re-relapse after the third course: cross-over to Arm 2: Start Eltrombopag (Revolade®), 50 mg PO until day 140 (details see Arm 2).

Arm 2: Study Arm Eltrombopag (Revolade®), 50 mg per os, from day 5-140. Tapering over 1 week from day 141-148 with 50 mg every second day.

In case of non-response after 4 weeks on eltrombopag: drop out

Eligibility criteria: Inclusion Criteria:

* Informed consent as documented by signature
* Newly diagnosed primary ITP according to the definition of Rodeghiero et al. and a risk of platelet count of \<30x109/l or risk of severe bleeding
* First-line therapy maximum for 1 week prior to enrolment
* Bleeding severity and quality of life are neither an inclusion nor an exclusion criterion.

Exclusion Criteria:

* Patients previously treated for ITP more than 7 days prior to enrolment (e.g. Steroid, intravenous immunoglobulin (IVIG), platelet infusion)
* Patients treated with second-line drugs prior to enrolment
* Life-threatening bleeding (and inability to sign informed consent)
* Secondary ITP
* Positive family history for ITP
* Presence or history of autoimmune disease as judged by the investigator
* Hepatosplenomegaly in the clinical examination
* Relevant hepatic disease as judged by the investigator
* Presence or history of thromboembolic disease
* Patients with splenectomy
* Women who are pregnant or breast feeding
* Intention to become pregnant during the course of the study
* Lack of safe double contraception
* Any vaccination 2 weeks prior start of the study
* Immunsuppressive and antiplatelet drugs
* Known or suspected non-compliance, drug or alcohol abuse
* Inability to follow the procedures of the study, e.g. due to language problems, psychological disorders, incompetence to judge
* Participation in another study with investigational drug within the 30 days preceding and during the present study
* Enrolment of the investigator, his/her family members, employees and other dependent persons

Primary outcomes:
measure: Change in percentual T-regulatory cells (Tregs)
timeFrame: before (Tregs/CD4), at week 3 and at the end of the treatment (week 20)
Secondary outcomes:
measure: Change in Th1/Th2 balance
timeFrame: at baseline and weeks 3, 20 and 30
measure: Clinical response to eltrombopag therapy
timeFrame: trial duration (baseline to week 30)
measure: Platelet response to eltrombopag
timeFrame: at baseline and weeks 6, 20 and 30
Other outcomes:
measure: Number of Adverse Events
timeFrame: trial duration (baseline to week 30)
measure: Severe bleeding
timeFrame: trial duration (baseline to week 30)
Locations:
city: Aarau
country: Switzerland
facility: Aarau Cantonal Hospital, Division of Hematology
city: Basel
country: Switzerland
facility: University Children's Hospital Basel (UKBB)
city: Basel
country: Switzerland
facility: University Hospital Basel, Division of Hematology
city: Bern
country: Switzerland
facility: University Hospital Bern, Division of Hematology
city: Liestal
country: Switzerland
facility: Liestal Cantonal Hospital, Division of Hematology
city: Lucerne
country: Switzerland
facility: Lucerne Cantonal Hospital, Division of Hematology
Study officials:
affiliation: University Children's Hospital Basel, UKBB
name: Alexandra Schifferli, Dr. med.
role: PRINCIPAL_INVESTIGATOR
References: