Romiplostim Plus Dexamethasone vs Dexamethasone in Patients With Newly Diagnosed Primary Immune Thrombocytopenia (RODEX)

March 15, 2024 updated by: Fundación Pública Andaluza para la gestión de la Investigación en Sevilla

A Multicentre, Randomized, Open-label Study of Romiplostim Plus Dexamethasone vs Dexamethasone in Patients With Newly Diagnosed Primary Immune Thrombocytopenia

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

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Estimated)

126

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

  • Name: María Eva Mingot Castellano, Hematologist
  • Phone Number: +34607933071
  • Email: memingot@gmail.com

Study Locations

  • Spain
      • Barcelona, Spain, 08003
      • Barcelona, Spain, 08035
        • Not yet recruiting
        • Centre Sociosanitari Sant Jordi de la Vall D'Hebron
        • Contact:
          • David Valcarcel Ferreiras
        • Contact:
      • Burgos, Spain, 09006
      • Coruña, Spain, 15006
      • Granada, Spain, 18014
        • Not yet recruiting
        • Hospital Universitario Virgen de las Nieves
        • Contact:
      • Madrid, Spain, 28007
        • Not yet recruiting
        • Hospital General Universitario Gregorio Marañon
        • Contact:
      • Madrid, Spain, 28046
        • Not yet recruiting
        • Compejo Hospitalario La Paz
        • Contact:
      • Madrid, Spain, 28922
      • Murcia, Spain, 30120
        • Not yet recruiting
        • Hospital Clínico Universitario Virgen de la Arrixaca
        • Contact:
      • Murcia, Spain, 3008
        • Recruiting
        • Hospital Universitario Morales Meseguer
        • Contact:
      • Málaga, Spain, 29010
      • Palma De Mallorca, Spain, 07120
        • Recruiting
        • Complejo Asistencial Son Espases
        • Contact:
      • Salamanca, Spain, 37007
        • Not yet recruiting
        • Complejo Asistencial Universitario de Salamanca
        • Contact:
      • Sevilla, Spain, 41013
      • Valencia, Spain, 46026

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: romiplostim plus dexamethasone (ROM + DEX)

Dexamethasone 40 mg daily x 4 days only in the first cycle and subcutaneous romiplostim weekly for up to 12 months

Romiplostim:

  1. The starting dose should be 3 mcg/kg/week. It could be start during de 4 days of dexamethasone.
  2. Patients will weekly receive dose increases of romiplostim in increments of 1 mcg/kg up to a maximum dose of 10 mcg/kg in an attempt to reach a target platelet count higher than 50x109/L.
  3. Otherwise, if platelets are lower than 50x109/L treatment with romiplostim will go on until Day 365 since randomization.
Drug: romiplostim plus dexamethasone
Patients will be reviewed weekly for 8 weeks (56 days). After Week 8, patients will be reviewed every 2 weeks (14 days) for 8 additional weeks and then monthly until Week 52 (365 days) from randomization.
Other Names:
  • ROM + DEX
Active Comparator: Dexamethasone (DEX)
Dexamethasone 40 mg daily x 4 days for up to 3 cycles every 14 to 28 days
Drug: Dexamethasone
Patients will be reviewed weekly until the completion of dexamethasone cycles and for a minimum of 8 weeks (56 days). After that, every 2 weeks (14 days) for 8 additional weeks and then monthly until Week 52 (365 days) from randomization.
Other Names:
  • DEX

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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)
Time Frame: 180 days after treatment withdrawal
Proportion of patients with platelets higher or equal than 50x109/L in the absence of any ITP treatment including any rescue treatment for at least 6 consecutive months (≥180 days) from treatment cessation and without World Health Organization grade 2 or more bleeding
180 days after treatment withdrawal

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
Time Frame: 180 days after treatment withdrawal
Proportion of patients with platelets higher or equal than 30x109/L in the absence of any ITP treatment including any rescue treatment for at least 6 consecutive months (≥180 days) from treatment cessation and without World Health Organization grade 2 or more bleeding.
180 days after treatment withdrawal
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.
Time Frame: 365 days after treatment withdrawal
Proportion of patients with platelets higher or equal than 30x109/L in the absence of any ITP treatment including any rescue treatment for at least 12 consecutive months (≥365 days) from treatment cessation and without World Health Organization grade 2 or more bleeding.
365 days after treatment withdrawal
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.
Time Frame: 365 days after treatment withdrawal
Proportion of patients with platelets higher or equal than 50x109/L in the absence of any ITP treatment including any rescue treatment for at least 12 consecutive months (≥365 days) from treatment cessation and without World Health Organization grade 2 or more bleeding.
365 days after treatment withdrawal
Proportion of patients with early response (ER)
Time Frame: Day 7
Proportion of patients with platelet count higher or equal than 30x109/L and at least double than baseline.
Day 7
Proportion of patients with initial response (IR)
Time Frame: Day 30
Proportion of patients with platelet count higher or equal than 30x109/L
Day 30
Proportion of patients with complete response (CR)
Time Frame: Day 180, Day 365, Day 545
Patients with platelet count ≥100x109/L and absence of bleeding symptoms.
Day 180, Day 365, Day 545
Proportion of patients with response (R)
Time Frame: Day 180, Day 365, Day 545
Patients with platelet count between 100x109/L and 30x109/L and at least doubled from baseline and absence of bleeding symptoms.
Day 180, Day 365, Day 545
Proportion of patients with global response (GR)
Time Frame: Day 180, Day 365, Day 545
Patients with platelet count ≥100x109/L and absence of bleeding symptoms or platelet count between 100x109/L and 30x109/L and at least doubled from baseline and absence of bleeding symptoms.
Day 180, Day 365, Day 545
Proportion of patients with targeted range (TR)
Time Frame: Day 180, Day 365, Day 545
Patients with platelet count between ≥30x109/L and ≤400x109/L.
Day 180, Day 365, Day 545
Time to loss of response (LoR) in patients who achieved response in both arms.
Time Frame: In every study visit, assessed up to 545 days
Number of days from the first time the patient achieved a platelet count ≥30x109/L until platelet count dropped below 30x109/L measured on 2 occasions with more than 1 day apart or presence of bleeding
In every study visit, assessed up to 545 days
Proportion of patients requiring any rescue treatment
Time Frame: In every study visit, assessed up to 545 days
Proportion of patients who need rescue treatments in each arm and total patients
In every study visit, assessed up to 545 days
Proportion and time to treatment failures
Time Frame: In every study visit, assessed up to 545 days
Proportion of patients who need rescue treatments and And the number of days they needed treatment
In every study visit, assessed up to 545 days
Proportion of patients with adverse events (AEs), including serious adverse events (SAEs) and laboratory safety parameters.
Time Frame: In every study visit, assessed up to 545 days
AEs will be graded according to National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. Bleeding events will be carefully monitored
In every study visit, assessed up to 545 days
Loss of productivity
Time Frame: In every study visit, assessed up to 545 days
Number of days of absenteeism from school or work and associated cost
In every study visit, assessed up to 545 days
Maximum number of consecutive days with platelet response
Time Frame: In every study visit, assessed up to 545 days
- The maximum number of consecutive days with platelet count between 100x109/L and 30x109/L in the total sample and in the absence of any rescue treatment
In every study visit, assessed up to 545 days
Maximum number of consecutive days with platelet complete response (CR)
Time Frame: In every study visit, assessed up to 545 days
- The maximum number of consecutive days with platelet count ≥100x109/L in the total sample and in the absence of any rescue treatment
In every study visit, assessed up to 545 days
Maximum number of consecutive days with platelet global response (GR)
Time Frame: In every study visit, assessed up to 545 days
The maximum number of consecutive days with platelet count ≥100x109/L or platelet count between 100x109/L and 30x109/L in the total sample and in the absence of any rescue treatment
In every study visit, assessed up to 545 days
Maximum number of consecutive days with platelet targeted range (TR)
Time Frame: In every study visit, assessed up to 545 days
The maximum number of consecutive days with platelet count between ≥30x109/L and ≤400x109/ L in the total sample and in the absence of any rescue treatment
In every study visit, assessed up to 545 days
Total number of days with platelet response
Time Frame: In every study visit, assessed up to 545 days
The total number od days with platelet count ≥100x109/L in the total sample and in the absence of any rescue treatment
In every study visit, assessed up to 545 days
Total number of days with platelet complete response (CR)
Time Frame: In every study visit, assessed up to 545 days
The total number od days with platelet count ≥100x109/L in the total sample and in the absence of any rescue treatment
In every study visit, assessed up to 545 days
Total number of days with platelet global response (GR
Time Frame: In every study visit, assessed up to 545 days
The total number od days with platelet count ≥100x109/L or platelet count between 100x109/L and 30x109/L in the total sample and in the absence of any rescue treatment
In every study visit, assessed up to 545 days
Total number of days with platelet targeted range (TR)
Time Frame: In every study visit, assessed up to 545 days
The total number od days with platelet count between ≥30x109/L and ≤400x109/ L in the total sample and in the absence of any rescue treatment
In every study visit, assessed up to 545 days
Changes in patients bleeding
Time Frame: Screning, Day 1, Week 8, Week 12, Moth 6, Moth 12 and End of study Visit
For the assessment of the of the patients' bleeding will be used immune thrombocytopenia-bleeding assessment tool (ITP-BAT): bleeding signs/symptoms are grouped in three domains (skin, visible mucosae and organs) and is graded from 0 (No) to 4.
Screning, Day 1, Week 8, Week 12, Moth 6, Moth 12 and End of study Visit
Changes in patients' quality of life- Short Form-36 Health Survey
Time Frame: Day 1, Week 8, Day 180, Day 365 and Day 545
For the assessment of the quality of life during the study will be used Short-Form-36 Health Survey: is a 36-item scale constructed to survey health-related 8 domains: limitations in physical activities due to health problems; limitations in social activities due to physical or emotional problems; limitations unusual role activities due to physical health problems; bodily pain; general mental health (psychological distress and well-being); limitations unusual role activities due to emotional problems; vitality (energy and fatigue); and general health perceptions.
Day 1, Week 8, Day 180, Day 365 and Day 545
Changes in patients' quality of life- FACIT-F
Time Frame: Day 1, Week 8, Day 180, Day 365 and Day 545
For the assessment of the quality of life during the study will be used FACIT-F (Fatigue Scale): is a short scale, 13-item, easy to administer tool that measures an individual's level of fatigue during their usual daily activities over the past week.The level of fatigue is measured by recording item responses ona 4-point Likert scale ranging from 0 "not at all" to 4 "very much.
Day 1, Week 8, Day 180, Day 365 and Day 545
Changes in patients' quality of life- ITP-Patient Assessment Questionnaire
Time Frame: Day 1, Week 8, Day 180, Day 365 and Day 545
For the assessment of the quality of life during the study will be used ITP-Patient Assessment Questionnaire): is a disease-specific instrument that was designed to measure the QoL of adult patients with immune thrombocytopenia. The instrument comprises 38 items completed by male respondents and 44 items completed by female respondents.
Day 1, Week 8, Day 180, Day 365 and Day 545
Healthcare resources use (HRU)
Time Frame: In every study visit, assessed up to 545 days

The data collected may be used to conduct exploratory economic analyses and may include:

  • Number of outpatient visits,
  • Number of home health care
  • Number of Hospitalization
  • Duration of medical care visits (days)
  • Number of Emergency room visits
  • Number of diagnostic procedures
  • Number of medical care visits
In every study visit, assessed up to 545 days

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Fundación Pública Andaluza para la gestión de la Investigación en Sevilla

Investigators

  • Principal Investigator: Charlotte Bradbury, Centre for Trials Research College of Biomedical & Life Sciences Cardiff University

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

December 2, 2022

Primary Completion (Estimated)

June 1, 2026

Study Completion (Estimated)

September 30, 2026

Study Registration Dates

First Submitted

March 7, 2022

First Submitted That Met QC Criteria

April 8, 2022

First Posted (Actual)

April 13, 2022

Study Record Updates

Last Update Posted (Actual)

March 18, 2024

Last Update Submitted That Met QC Criteria

March 15, 2024

Last Verified

March 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • RODEX
  • 2021-006970-22 (EudraCT Number)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

The results will be shared with the investigators involved in the study, and will be shared when the analysis of the results is performed.

IPD Sharing Time Frame

Along the study

IPD Sharing Access Criteria

Direct collaborators within the study

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL
  • SAP
  • ICF
  • ANALYTIC_CODE
  • CSR

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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