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The PROLONG Trial - Rituximab Maintenance Therapy in ITP

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ClinicalTrials.gov Identifier: NCT03010202
Recruitment Status : Recruiting
First Posted : January 4, 2017
Last Update Posted : May 15, 2019
Sponsor:
Collaborators:
Oslo University Hospital
St. Olavs Hospital
Helse Stavanger HF
University Hospital of North Norway
Haukeland University Hospital
Odense University Hospital
Hammersmith Hospitals NHS Trust
Centre Hôpital Universitaire Farhat Hached
Henri Mondor University Hospital
University Hospital, Akershus
Information provided by (Responsible Party):
Ostfold Hospital Trust

Tracking Information
First Submitted Date  ICMJE December 28, 2016
First Posted Date  ICMJE January 4, 2017
Last Update Posted Date May 15, 2019
Study Start Date  ICMJE December 2016
Estimated Primary Completion Date December 2023   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: January 3, 2017)
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).
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT03010202 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: January 3, 2017)
  • 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).
  • 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).
  • 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).
  • 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
  • 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)
  • 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).
  • 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).
  • 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).
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE The PROLONG Trial - Rituximab Maintenance Therapy in ITP
Official Title  ICMJE Prolonging the Response by Low-dose Rituximab Maintenance Therapy in Immune Thrombocytopenia: a Randomized Placebo-controlled Trial - the PROLONG Trial
Brief Summary 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.
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  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Purpura, Thrombocytopenic, Idiopathic
Intervention  ICMJE
  • Drug: Dexamethasone
    Comparing the effect of Rituximab infusion With or without Dexamethasone
  • Drug: Rituximab
    Comparing maintenance dose of 500mg Rituximab at week 1 and week 24 to Placebo
    Other Name: Mabthera
Study Arms  ICMJE
  • 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.
    Intervention: Drug: 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
    Intervention: Drug: Rituximab
  • No Intervention: Maintenance phase: Placebo
    Infusion of normal saline 0,9% in week 1 ande week 24 in second randomization.
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: January 3, 2017)
100
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE December 2023
Estimated Primary Completion Date December 2023   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.

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Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Waleed Ghanima, PhD +47 41303440 wghanima@gmail.com
Contact: Pål André Holme, PhD
Listed Location Countries  ICMJE Norway
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03010202
Other Study ID Numbers  ICMJE RGCH004
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: Undecided
Responsible Party Ostfold Hospital Trust
Study Sponsor  ICMJE Ostfold Hospital Trust
Collaborators  ICMJE
  • Oslo University Hospital
  • St. Olavs Hospital
  • Helse Stavanger HF
  • University Hospital of North Norway
  • Haukeland University Hospital
  • Odense University Hospital
  • Hammersmith Hospitals NHS Trust
  • Centre Hôpital Universitaire Farhat Hached
  • Henri Mondor University Hospital
  • University Hospital, Akershus
Investigators  ICMJE
Principal Investigator: Waleed Ghanima, PhD Ostfold Hospital Trust
PRS Account Ostfold Hospital Trust
Verification Date May 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP