Clinical trial NCT05325593: Romiplostim Plus Dexamethasone vs Dexamethasone in Patients With Newly Diagnosed Primary Immune Thrombocytopenia
Official title: A Multicentre, Randomized, Open-label Study of Romiplostim Plus Dexamethasone vs Dexamethasone in Patients With Newly Diagnosed Primary Immune Thrombocytopenia
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: Primary Immune Thrombocytopenia
Keywords: Romiplostim
Dexamethasone
Lead sponsor: Fundación Pública Andaluza para la gestión de la Investigación en Sevilla
Sponsor class: OTHER
First posted: 2022-04-13
Enrollment: 129
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Parallel Assignment Randomized 1:1
Primary purpose: TREATMENT

Brief summary: Phase III, open-labeled, randomized and multicenter clinical trial to evaluate the superiority of romiplostim plus dexamethasone vs dexamethasone alone in patients with newly diagnosed primary immune thrombocytopenia

Detailed description: The main objective of the study is to evaluate the superiority of romiplostim plus dexamethasone versus dexamethasone alone in the treatment of primary immune thrombocytopenia, with sustained response to any ITP treatment and without World Health Organization grade 2 or higher bleeding, after six months from cessation of treatment.

Maximum time on treatment with romiplostim will be 12 months (365 days). Then, patients will be followed up for 6 additional months (180 days) after stopping romiplostim.

Clinical rules are included if romiplostim dose should be modified or finished. In case of dexamethasone, no dose adjustment is permitted.

The evaluation of romiplastim plus dexamethasone´s superiority in different periods and platelet count, proportion of patients with complete response (CR), global response (GR), early response (ER) and initial response (IR); time to loss of response (LoR), adverse events, quality of life and healthcare resources use are included as secondary objectives.

Eligibility criteria: Main inclusion criteria:

1. Age ≥ 18 years of age at the time of signing informed consent.
2. Newly diagnosis of primary ITP according to the International Working Group assessment \[1\] and previously untreated for ITP.
3. Platelet counts \<30x109/L or ITP with platelet counts \<50x109/L and concomitant bleeding symptoms.
4. Serum creatinine concentration ≤1.5 mg/dL.

Main exclusion criteria:

1. World Health Organization's performance status \>2.
2. Previous therapy with rituximab (within 3 months previous of study enrollment), corticosteroids or, therapy with other immunomodulating agents within 1 month before of enrolment;,prior use of hematopoietic analogs and or fostamatinib for any other reason despite ITP three months before enrolment.
3. Previous use of romiplostim, polyethylene glycol-recombinant human megakaryocyte growth and development factor, Eltrombopag, recombinant human anti-thrombopoietin, or any platelet-producing agent three months before enrolment.
4. Alkylating agents within 8 weeks before the screening visit or anticipated use during the time of the proposed study.
5. Splenectomy within 3 months of the screening visit or planned splenectomy during study period.
6. Abnormal renal function (serum creatinine \> 1.5 mg/dL).
7. Active hepatic disease (evidenced by alanine aminotransferase \[ALT\] or aspartate aminotransferase \[AST\] levels \>5 times the upper limit of normal (it will only be necessary to determine one of the two transaminases
8. Severe chronic liver disease as evidenced by, but not limited to, any of the following: International Normalized Ratio \>1.4, hypoalbuminemia, portal vein hypertension including presence of otherwise unexplained splenomegaly and history of esophageal varices.
9. Patients with known immunoglobulin M seropositive tests for cytomegalovirus and/or Epstein-Barr virus in the previous month.
10. Patients with an active viral infection at screening with: Hepatitis B Virus, Hepatitis C Virus, detectable virus charge of HIV.
11. Intolerance to dexamethasone.
12. History of a bone marrow stem cell disorder.
13. Active or prior malignancy except adequately treated (ie, complete surgical excision with negative margins) basal cell carcinoma.
14. History of helicobacter pylori by urea breath test or stool antigen test within 6 months of enrollment, if available.
15. History of myelodysplastic syndrome, systemic lupus erythematosus, or autoimmune cytopenia.
16. History of antiphospholipid antibody syndrome.
17. History of disseminated intravascular coagulation, hemolytic uremic syndrome, or thrombotic thrombocytopenic purpura.
18. History of deep or superficial venous thromboembolism in the last 12 months or stroke, acute ischaemic heart disease or acute peripheral vascular disease in the last 6 months.
19. Hypersensitivity to any recombinant Escherichia coli-derived product (eg, Infergen, Neupogen, Somatropin, and Actimmune) or known sensitivity to any of the products to be administered during dosing
20. Currently enrolled in another investigational device or drug study or \< 30 days since ending another investigational device or drug studies, or receiving other investigational agents.
21. Will have any other investigational procedures performed while enrolled in this clinical study.
22. Pregnant or breastfeeding, or planning to become pregnant or breastfeed during treatment or within 1 month after the end of treatment.
23. Female subject of childbearing potential is not willing to use, in combination with her partner, an acceptable method of effective contraception during treatment and for 1 month after the end of treatment. Females of childbearing potential should only be included after a negative, pregnancy test.
24. Will not be available for protocol-required study visits, to the best of the subject's and investigator's knowledge.
25. Any kind of disorder that, in the opinion of the investigator, may compromise the ability of the subject to give written informed consent and/or to comply with all required study procedures.
26. Other serious comorbidities at investigator criteria.

Primary outcomes:
measure: Proportion of patients achieving sustain response out of treatment with platelets higher or equal than 30x109/L for 6 months (Sustained Response Off any ITP Treatment)
timeFrame: 180 days after treatment withdrawal
Secondary outcomes:
measure: Proportion of patients achieving sustain response out of treatment with platelets higher or equal than 30x109/L for 6 months in the absence of any ITP treatment including any rescue treatment.
timeFrame: 180 days after treatment withdrawal
measure: Proportion of patients achieving sustain response out of treatment with platelets higher or equal than 30x109/L for 12 months in the absence of any ITP treatment including any rescue treatment.
timeFrame: 365 days after treatment withdrawal
measure: Proportion of patients achieving sustain response out of treatment with platelets higher or equal than 50x109/L for 12 months in the absence of any ITP treatment including any rescue treatment.
timeFrame: 365 days after treatment withdrawal
measure: Proportion of patients with early response (ER)
timeFrame: Day 7
measure: Proportion of patients with initial response (IR)
timeFrame: Day 30
measure: Proportion of patients with complete response (CR)
timeFrame: Day 180, Day 365, Day 545
measure: Proportion of patients with response (R)
timeFrame: Day 180, Day 365, Day 545
measure: Proportion of patients with global response (GR)
timeFrame: Day 180, Day 365, Day 545
measure: Proportion of patients with targeted range (TR)
timeFrame: Day 180, Day 365, Day 545
measure: Time to loss of response (LoR) in patients who achieved response in both arms.
timeFrame: In every study visit, assessed up to 545 days
measure: Proportion of patients requiring any rescue treatment
timeFrame: In every study visit, assessed up to 545 days
measure: Proportion and time to treatment failures
timeFrame: In every study visit, assessed up to 545 days
measure: Proportion of patients with adverse events (AEs), including serious adverse events (SAEs) and laboratory safety parameters.
timeFrame: In every study visit, assessed up to 545 days
measure: Changes in patients bleeding
timeFrame: Screning, Day 1, Week 8, Week 12, Moth 6, Moth 12 and End of study Visit
measure: Changes in patients' quality of life- Short Form-36 Health Survey
timeFrame: Day 1, Week 8, Day 180, Day 365 and Day 545
measure: Changes in patients' quality of life- FACIT-F
timeFrame: Day 1, Week 8, Day 180, Day 365 and Day 545
measure: Changes in patients' quality of life- ITP-Patient Assessment Questionnaire
timeFrame: Day 1, Week 8, Day 180, Day 365 and Day 545
measure: Healthcare resources use (HRU)
timeFrame: In every study visit, assessed up to 545 days
measure: Loss of productivity
timeFrame: In every study visit, assessed up to 545 days
measure: Maximum number of consecutive days with platelet response
timeFrame: In every study visit, assessed up to 545 days
measure: Maximum number of consecutive days with platelet complete response (CR)
timeFrame: In every study visit, assessed up to 545 days
measure: Maximum number of consecutive days with platelet global response (GR)
timeFrame: In every study visit, assessed up to 545 days
measure: Maximum number of consecutive days with platelet targeted range (TR)
timeFrame: In every study visit, assessed up to 545 days
measure: Total number of days with platelet response
timeFrame: In every study visit, assessed up to 545 days
measure: Total number of days with platelet complete response (CR)
timeFrame: In every study visit, assessed up to 545 days
measure: Total number of days with platelet global response (GR
timeFrame: In every study visit, assessed up to 545 days
measure: Total number of days with platelet targeted range (TR)
timeFrame: In every study visit, assessed up to 545 days
Other outcomes:
Locations:
city: Bologna
country: Italy
facility: IRCCS AOU di Bologna, Seràgnoli Institute of Hematology
city: Milano
country: Italy
facility: ASST Fatebenefratelli Sacco - Ospedale L. Sacco
city: Milano
country: Italy
facility: Grande Ospedale Metropolitano Niguarda
city: Rome
country: Italy
facility: Azienda Ospedaliero-Universitaria Policlinico Umberto I / SAPIENZA Universitá di Roma
city: Rome
country: Italy
facility: Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico
city: Rome
country: Italy
facility: Fondazione Policlinico Universitario Agostino Gemelli IRCCS
city: Barcelona
country: Spain
facility: Hospital del Mar
city: Barcelona
country: Spain
facility: Centre Sociosanitari Sant Jordi de la Vall D'Hebron
city: Burgos
country: Spain
facility: Complejo Asistencial Universitario de Burgos
city: Coruña
country: Spain
facility: Complejo Hospitalario Universitario A Coruña
city: Granada
country: Spain
facility: Hospital Universitario Virgen de las Nieves
city: Madrid
country: Spain
facility: Hospital General Universitario Gregorio Marañón
city: Madrid
country: Spain
facility: Compejo Hospitalario La Paz
city: Madrid
country: Spain
facility: Hospital Universitario Fundación Alcorcon
city: Murcia
country: Spain
facility: Hospital Universitario Morales Meseguer
city: Murcia
country: Spain
facility: Hospital Clínico Universitario Virgen de la Arrixaca
city: Málaga
country: Spain
facility: Hospital Universitario Virgen de la Victoria
city: Palma De Mallorca
country: Spain
facility: Complejo Asistencial Son Espases
city: Salamanca
country: Spain
facility: Complejo Asistencial Universitario de Salamanca
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen del Rocío
city: Valencia
country: Spain
facility: Hospital Universitario y Pilitécnico La Fe
city: Birmingham
country: United Kingdom
facility: University Hospitals Birmingham NHS Foundation Trust
city: Bristol
country: United Kingdom
facility: University Hospitals Bristol and Weston NHS Trust
city: Canterbury
country: United Kingdom
facility: Haemophilia and Thrombosis Centre, Kent & Canterbury Hospital, Kent & Canterbury Hospital, Ethelbert Road, Canterbury, CT1 3NG, England, UK
city: London
country: United Kingdom
facility: Greater Glasgow and Clyde Health Board
city: Newcastle
country: United Kingdom
facility: Haematology, Royal Victoria Infirmary
city: Norwich
country: United Kingdom
facility: Norfolk & Norwich University Hospital Trust
city: Oxford
country: United Kingdom
facility: Oxford University Hospitals NHS Foundation Trust
city: Plymouth
country: United Kingdom
facility: "Haematology, Derriford Hospital, University Hospitals Plymouth NHS Trust
city: Torquay
country: United Kingdom
facility: Torbay and South Devon NHS Foundation Trust
Study officials:
affiliation: Centre for Trials Research College of Biomedical & Life Sciences Cardiff University
name: Charlotte Bradbury
role: PRINCIPAL_INVESTIGATOR
References: