The PROLONG Trial - Rituximab Maintenance Therapy in ITP

NCT03010202 | Unknown Phase 3 DMC

• 1 other identifier: RGCH004
• Study Type: interventional
• Target: 136
• Locations: 1 country
• Sites: 1

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.

Conditions

Purpura, Thrombocytopenic, Idiopathic

Keywords

immune thrombocytopenia; rituximab; thrombocytopenia

Outcome Measures

Primary Outcomes (1)

• Sustained of overall response

  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 Outcomes (8)

• Improvement at overall response rate in week 24

  Week 24 (+/- 2 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)

  24 weeks and 52 weeks

• Sustained Complete Response (CR) during maintenance phase

  52 weeks

• Complete Response during induction phase

  24 weeks (+/- 2 weeks)

Study Arms (4)

Induction phase: Rituximab+Dexamethasone

EXPERIMENTAL

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

Induction phase: Rituximab

NO INTERVENTION

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

Maintenance phase: Rituximab

EXPERIMENTAL

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

Maintenance phase: Placebo

NO INTERVENTION

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

Interventions

Dexamethasone DRUG

Comparing the effect of Rituximab infusion With or without Dexamethasone

Induction phase: Rituximab+Dexamethasone

Rituximab DRUG

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

Also known as: Mabthera

Maintenance phase: Rituximab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female aged ≥18 years.
• Scheduled intravenous treatment of rituximab.
• Signed and dated written informed consent.
• Females of child-bearing potential accepting to follow effective contraceptive methods for at least 12 months following the last administration of rituximab or placebo.
• Completion of the induction phase (phase 1) of the study.
• Sustained response at the end of phase 1.
• Randomization within 4 weeks after the completion of phase 1, i.e. between week 24 and 28.

You may not qualify if:

• Previous treatment for ITP with: rituximab, other immune suppressants (including mycophenolate mofetil, aziothioprin, cyclosporine), chemotherapy or splenectomy.
• Pregnancy or lactation.
• Known active gastro-duodenal ulcer.
• 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.
• Concomitant autoimmune hemolytic anemia.
• 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.
• Active hepatitis B virus or patients with positive HBsAG or HBcAB.
• 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.
• Known allergy and/or sensitivity or contraindication to rituximab or dexamethasone or any of the ingredients.
• Patients in a severely immune compromised state.
• Known contraindication to a treatment with any proton-pump inhibitor.
• Active malignancy or history of malignant disease during the last 2 years except cured skin cancer.
• 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.
• \. 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.

Sponsors & Collaborators

• Ostfold Hospital Trust: lead
• Oslo University Hospital: collaborator
• St. Olavs Hospital: collaborator
• Helse Stavanger HF: collaborator
• University Hospital of North Norway: collaborator
• Haukeland University Hospital: collaborator
• Odense University Hospital: collaborator
• Centre Hôpital Universitaire Farhat Hached: collaborator
• Henri Mondor University Hospital: collaborator
• University Hospital, Akershus: collaborator
• Cairo University: collaborator

Study Sites (1)

Ostfold Hospital Trust

Sarpsborg, 1714, Norway

Location

MeSH Terms

Conditions

Purpura, Thrombocytopenic, Idiopathic; Thrombocytopenia

Interventions

Dexamethasone; Rituximab

Condition Hierarchy (Ancestors)

Purpura, Thrombocytopenic; Purpura; Blood Coagulation Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Thrombotic Microangiopathies; Blood Platelet Disorders; Cytopenia; Hemorrhagic Disorders; Autoimmune Diseases; Immune System Diseases; Hemorrhage; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Skin Manifestations; Signs and Symptoms

Intervention Hierarchy (Ancestors)

Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated; Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Waleed Ghanima, PhD

  Ostfold Hospital Trust

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 28, 2016
• First Posted: January 4, 2017
• Study Start: December 1, 2016
• Primary Completion: December 1, 2024
• Study Completion: December 1, 2024
• Last Updated: May 29, 2024

Record last verified: 2023-11

Data Sharing

• IPD Sharing: Will not share

Locations

NO (1)