The PROLONG Trial - Rituximab Maintenance Therapy in ITP

NCT ID: NCT03010202

Last Updated: 2024-05-29

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE3
• Total Enrollment: 136 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-12-31
• Study Completion Date: 2024-12-31

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).

Conditions

Purpura, Thrombocytopenic, Idiopathic

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

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.

Group Type: EXPERIMENTAL

Dexamethasone

Intervention Type: DRUG

Comparing the effect of Rituximab infusion With or without Dexamethasone

Induction phase: Rituximab

Open-label, intravenous infusions of rituximab 1000 mg given on day 1 and day 15.

Group Type: NO_INTERVENTION

No interventions assigned to this group

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

Group Type: EXPERIMENTAL

Rituximab

Intervention Type: DRUG

Comparing maintenance dose of 500mg Rituximab at week 1 and week 24 to Placebo

Maintenance phase: Placebo

Infusion of normal saline 0,9% in week 1 ande week 24 in second randomization.

Group Type: NO_INTERVENTION

No interventions assigned to this group

Interventions

Dexamethasone

Comparing the effect of Rituximab infusion With or without Dexamethasone

Intervention Type: DRUG

Rituximab

Comparing maintenance dose of 500mg Rituximab at week 1 and week 24 to Placebo

Intervention Type: DRUG

Other Intervention Names

Mabthera

Eligibility Criteria

Inclusion Criteria

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.

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

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.

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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• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Oslo University Hospital

OTHER

Sponsor Role: collaborator

St. Olavs Hospital

OTHER

Sponsor Role: collaborator

Helse Stavanger HF

OTHER_GOV

Sponsor Role: collaborator

University Hospital of North Norway

OTHER

Sponsor Role: collaborator

Haukeland University Hospital

OTHER

Sponsor Role: collaborator

Odense University Hospital

OTHER

Sponsor Role: collaborator

Centre Hôpital Universitaire Farhat Hached

OTHER

Sponsor Role: collaborator

Henri Mondor University Hospital

OTHER

Sponsor Role: collaborator

University Hospital, Akershus

OTHER

Sponsor Role: collaborator

Cairo University

OTHER

Sponsor Role: collaborator

Ostfold Hospital Trust

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Waleed Ghanima, PhD

Role: PRINCIPAL_INVESTIGATOR

Ostfold Hospital Trust

Locations

Ostfold Hospital Trust

Sarpsborg, , Norway

Countries

Norway

Other Identifiers

RGCH004

Identifier Type: -

Identifier Source: org_study_id