Clinical trial NCT04588194: Romiplostim, Rituximab and Dexamethasone as Frontline Treatment for Immune Thrombocytopenia
Official title: Romiplostim in Combination With Low-dose Rituximab and High-dose Dexamethasone as Frontline Treatment for Immune Thrombocytopenia
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Immune Thrombocytopenia
Thrombotic Thrombocytopenic Purpura
Keywords: thrombocytopenia
Lead sponsor: Hospital Universitario Dr. Jose E. Gonzalez
Sponsor class: OTHER
First posted: 2020-10-19
Enrollment: 12
Sex: ALL
Minimum age (years): 16
Maximum age (years): 90
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to determine the response rate and response duration with the combination of low-dose rituximab, romiplostim and high-dose dexamethasone.

Detailed description: Immune thrombocytopenia is an autoimmune disorder characterized by formation of autoantibodies against platelet antigens leading platelet destruction.

Corticosteroids increase the platelet count in about 80 percent of patients. However, many patients have a relapse when the dose of corticosteroid is reduced. Debilitating side effects are common in patients who require long-term corticosteroid therapy to maintain the platelet count. Romiplostim, it is a small molecule agonist of the c-mpl (TpoR) receptor, which is the physiological target of the hormone thrombopoietin, has been shown to be effectively raise the platelet count in adult patients (aged 18 years and over) who have had their spleen removed or where splenectomy is not an option and have received prior treatment with corticosteroids or immunoglobulins, and these medicines did not work (refractory ITP). There are a few case reports where romiplostim an option as first line treatment for IT.

The purpose of this study is to determine the response rate and response duration with the combination of rituximab (100 mg weekly four weeks), romiplostim (2mcg/Kg four weekly) and high-dose dexamethasone (40mg PO days 1-4) in untreated adult patients with \<30\*109/L platelet count diagnosed with immune thrombocytopenia.

A complete response is defined as an increase in platelet counts to \>150×109/L on two consecutive occasions. A clinical response is defined as an increase in the platelet count between \>30×109/L on two consecutive measures and no bleeding. Duration of response is considered from the day of the initial administration to the first time of relapse (platelet count \<30×109/L) or to time of analysis Patients will be evaluated each week during 4 weeks and then every month for at least 6 months.

Eligibility criteria: Inclusion Criteria:

* Clinically confirmed immune thrombocytopenia (IT) Platelet count less than 30,000/mm3 on two occasions.
* Subject ≥ 16 years
* Subject has signed and dated written informed consent.

Exclusion Criteria:

* Previous treatment (only corticosteroids at dose or prednisone equivalent of 300 mg)
* Performance status above or equal to 2.
* Pregnancy and lactation
* Previous splenectomy
* Connective tissue disease
* Autoimmune hemolytic anemia
* Relapse
* Active infection, sepsis or fever
* Positive for hepatitis B virus or hepatitis C virus or human immunodeficiency virus.

Primary outcomes:
measure: Clinical Response
timeFrame: 28 days
Secondary outcomes:
measure: Complete Response
timeFrame: 28 days
Other outcomes:
Locations:
city: Monterrey
country: Mexico
facility: Servicio de Hematología, Hospital Universitario "Dr. José Eleuterio González", Universidad Autónoma de Nuevo León
state: Nuevo León
Study officials:
affiliation: Hospital Universitario J. Eleuterio González
name: David Gómez, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Gomez-Almaguer D, Herrera-Rojas MA, Jaime-Perez JC, Gomez-De Leon A, Cantu-Rodriguez OG, Gutierrez-Aguirre CH, Tarin-Arzaga L, Hernandez-Reyes J, Ruiz-Arguelles GJ. Eltrombopag and high-dose dexamethasone as frontline treatment of newly diagnosed immune thrombocytopenia in adults. Blood. 2014 Jun 19;123(25):3906-8. doi: 10.1182/blood-2014-01-549360. Epub 2014 May 6.
citation: Gomez-Almaguer D, Tarin-Arzaga L, Moreno-Jaime B, Jaime-Perez JC, Ceballos-Lopez AA, Ruiz-Arguelles GJ, Ruiz-Delgado GJ, Cantu-Rodriguez OG, Gutierrez-Aguirre CH, Sanchez-Cardenas M. High response rate to low-dose rituximab plus high-dose dexamethasone as frontline therapy in adult patients with primary immune thrombocytopenia. Eur J Haematol. 2013 Jun;90(6):494-500. doi: 10.1111/ejh.12102. Epub 2013 Apr 2.
citation: Cooper N, Terrinoni I, Newland A. The efficacy and safety of romiplostim in adult patients with chronic immune thrombocytopenia. Ther Adv Hematol. 2012 Oct;3(5):291-8. doi: 10.1177/2040620712453596.
citation: Vishnu P, Aboulafia DM. Long-term safety and efficacy of romiplostim for treatment of immune thrombocytopenia. J Blood Med. 2016 May 25;7:99-106. doi: 10.2147/JBM.S80646. eCollection 2016.