The PROLONG Trial - Rituximab Maintenance Therapy in ITP

May 28, 2024 updated by: Ostfold Hospital Trust

Prolonging the Response by Low-dose Rituximab Maintenance Therapy in Immune Thrombocytopenia: a Randomized Placebo-controlled Trial - the PROLONG Trial

This study is a two phase study that aims to evaluate if low-dose Rituximab maintenance therapy may prolong the the effect of Rituximab in immune thrombocytopenia.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Active, not recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

This is a multi-center, international, randomized, two-phase study:

First phase (induction phase) is open-label, hypothesis-generating, involving 1:1 randomization into: rituximab (group 1) or rituximab plus dexamethasone (group 2) to determine if the response to rituximab can be improved by the addition of dexamethasone.

Second Phase (maintenance phase) is the main part of the study, involving 1:1 double-blind randomization into low dose rituximab or placebo to determine if the response achieved in the first phase can be prolonged by administrating maintenance treatment with low dose rituximab.

Primary objective:

To determine if maintenance therapy with low-dose rituximab is superior to placebo in prolonging responses among ITP patients who achieved an initial response with rituximab.

Secondary objectives:

  1. To explore if the initial overall response rate, at week 24, can be improved by at least 10% by adding dexamethasone to rituximab (induction phase).
  2. To assess the safety of study treatment, especially infectious episodes (induction & maintenance phases).
  3. To assess bleeding complications during the study (induction & maintenance phases).
  4. To assess the use of rescue medications and other platelet-elevating therapies during the study (induction & maintenance phases).
  5. To determine rate of Complete Response (CR) during induction phase and sustained CR during maintenance phase (induction & maintenance phases).
  6. To determine the duration of overall response and CR (induction & maintenance phases).
  7. To assess health-related quality of life and fatigue (induction & maintenance phases).

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
136

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • 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

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.
  • Name: Pål André Holme, PhD

Study Locations

  • Norway
      • Sarpsborg, Norway, 1714
        • Ostfold Hospital Trust

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

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria First randomization (Induction phase):

  1. Male or female aged ≥18 years.
  2. Diagnosis of primary ITP of less than one year duration having a platelet count of ≤ 30 x109/L measured within 4 weeks prior to inclusion with failure to achieve initial response or relapse either after one cycle of dexamethasone (40 mg daily for 4 days) or 4 weeks with any other steroid (prednisone or prednisolone). Platelet count between 31 to 50 x109/L is accepted if higher platelet count is required due to concomitant antiplatelet therapy or bleeding.
  3. Scheduled intravenous treatment of rituximab.
  4. Signed and dated written informed consent.
  5. Females of child-bearing potential accepting to follow effective contraceptive methods for at least 12 months following the last administration of rituximab or placebo.

Inclusion criteria second randomization (maintenance phase):

  1. Completion of the induction phase (phase 1) of the study.
  2. Sustained response at the end of phase 1.
  3. Randomization within 4 weeks after the completion of phase 1, i.e. between week 24 and 28.

Exclusion Criteria first randomization (Induction phase):

  1. Previous treatment for ITP with: rituximab, other immune suppressants (including mycophenolate mofetil, aziothioprin, cyclosporine), chemotherapy or splenectomy.
  2. Pregnancy or lactation.
  3. Known active gastro-duodenal ulcer.
  4. Secondary ITP: ITP associated with lymphoma, chronic lymphocytic leukemia, autoimmune disorders such as, common variable immune deficiency, human immunodeficiency virus, or hepatitis C or thrombocytopenia associated with myeloid dysplasia.
  5. Concomitant autoimmune hemolytic anemia.
  6. History of any major cardiovascular event within the 6 months prior to randomization, including but not limited to: myocardial infarction, unstable angina, cerebrovascular accident, or New York Heart Association Class III or IV heart failure.
  7. Active hepatitis B virus or patients with positive HBsAG or HBcAB.
  8. Patients with active severe infection, including systemic mycotic infections or a history of recurring or chronic infections or with underlying conditions which may further predispose patients to serious infection.
  9. Known allergy and/or sensitivity or contraindication to rituximab or dexamethasone or any of the ingredients.
  10. Patients in a severely immune compromised state.
  11. Known contraindication to a treatment with any proton-pump inhibitor.
  12. Active malignancy or history of malignant disease during the last 2 years except cured skin cancer.
  13. Patients with history of poor compliance or history of alcohol/drug abuse or excessive alcohol beverage consumption that would interfere with the ability to comply with the study protocol, or current or past psychiatric disease that might interfere with the ability to comply with the study protocol or give informed consent.

Exclusion criteria second randomization (maintenance phase) 14. Severe allergic reaction or serum sickness due to rituximab in phase 1 of the study.

15. Pregnancy. 16. Treatment with rescue medication after week 18. 17. Patients refusing to continue in the study (withdrawal of consent). 18. Splenectomy performed for any cause.

-

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: Quadruple

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Induction phase: Rituximab+Dexamethasone
Open-label, intravenous infusions of rituximab 1000 mg and oral dexamethasone 20 mg daily for 4 days given on day 1 and day 15.
Drug: Dexamethasone
Comparing the effect of Rituximab infusion With or without Dexamethasone
No Intervention: Induction phase: Rituximab
Open-label, intravenous infusions of rituximab 1000 mg given on day 1 and day 15.
Experimental: Maintenance phase: Rituximab
Patients who respond to rituximab in the induction phase will be proceed into the maintenance phase and randomized to rituximab infusion of 500 mg in week 1 and week 24, or
Drug: Rituximab
Comparing maintenance dose of 500mg Rituximab at week 1 and week 24 to Placebo
Other Names:
  • Mabthera
No Intervention: Maintenance phase: Placebo
Infusion of normal saline 0,9% in week 1 ande week 24 in second randomization.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Sustained of overall response
Time Frame: 52 weeks
sustained overall response during maintenance phase [loss of overall response is defined as: (1) two consecutive measurements with platelet counts < 50 x 109/L taken at 1-8-week interval, and/or, (2) use of any ITP-directed therapies, other than study medication, because of bleeding or thrombocytopenia, except for preoperative elevation of platelet count] (this endpoint applies to maintenance phase only).
52 weeks

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Improvement at overall response rate in week 24
Time Frame: Week 24 (+/- 2 weeks)
Overall response during induction phase defined as mean platelet count, determined in week 24 (± 2 weeks) after induction therapy, > 50 x 10E9/L , without use of any other ITP-directed therapies after week 12 following the first randomization (this endpoint applies to induction phase only).
Week 24 (+/- 2 weeks)
Safety assessed by the frequency of > grade II adverse events (this endpoint applies to both phases)
Time Frame: 24 weeks and 52 weeks
Safety assessed by the frequency of > grade II adverse events (this endpoint applies to both phases).
24 weeks and 52 weeks
Grade of bleeding during the study (during both phases)
Time Frame: 24 weeks and 52 weeks
Grade of bleeding (this endpoint applies to both phases).
24 weeks and 52 weeks
Sustained Complete Response (CR) during maintenance phase
Time Frame: 52 weeks
Sustained Complete Response (CR) during maintenance phase defined as platelet count > 100 x 109/L maintained during maintenance phase, without the use of any ITP-directed therapies
52 weeks
Complete Response during induction phase
Time Frame: 24 weeks (+/- 2 weeks)
Complete Response (CR) during induction phase defined as platelet count, determined in week 24 (± 2 weeks), > 100 x 109/L without use of any other ITP-directed therapies after week 12 following the first randomization (induction phase)
24 weeks (+/- 2 weeks)
Rescue medication or other elevating platelet therapy
Time Frame: after 12 weeks in induction phase and 40 weeks in maintenance phase

Administration of rescue medication or other elevating platelet therapy

  1. After week 12 (induction phase)
  2. During maintenance phase (maintenance phase).
after 12 weeks in induction phase and 40 weeks in maintenance phase
Platelet count Levels > 50 x 109/L during maintenance phase
Time Frame: phase 2 (52 weeks)
Percentage of patients with more than 80% of platelet counts level > 50 x 109/L during the maintenance phase (this endpoint applies to maintenance phase only).
phase 2 (52 weeks)
Health related quality of life
Time Frame: First phase at 24 weeks and second phase at 52 weeks
Health-related quality of life assessed by SF-36 questionnaire (this endpoint applies to both phases).
First phase at 24 weeks and second phase at 52 weeks

Collaborators and Investigators

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

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Ostfold Hospital Trust

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Odense University Hospital
Oslo University Hospital
Cairo University
University Hospital of North Norway
Helse Stavanger HF
Haukeland University Hospital
St. Olavs Hospital
University Hospital, Akershus
Henri Mondor University Hospital
Centre Hôpital Universitaire Farhat Hached

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Waleed Ghanima, PhD, Ostfold Hospital Trust

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

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
December 1, 2016

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
December 1, 2024

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
December 1, 2024

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
December 28, 2016

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
January 3, 2017

First Posted (Estimated)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
January 4, 2017

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
May 29, 2024

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
May 28, 2024

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
November 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • RGCH004

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

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.

Clinical Trials on Purpura, Thrombocytopenic, Idiopathic

Clinical Trials on Dexamethasone

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

Cookie Settings

We use cookies to ensure that we give you the best experience on our website. For more details carefully read our Privacy and Cookies Policy. ...>>>You can change your preferences or withdraw your consent at any time by deleting the cookies from your website or computer as described in the policy. Please accept it and choose your preferences by ticking the corresponding boxes in the "Manage Settings" section below. Please carefully read our Terms of Service before you proceed with using any part of this website.
«Manage Settings