Immune ThrombocytopeniaRITUX PLUSNCT03154385
Efficacy and Safety Assessment of a Treatment Combining Rituximab and Belimumab in Adults With Persistent Immune Thrombocytopenia
A study testing Rituximab (Mabthera ®) Belimumab (Benlysta ®) in people with Immune Thrombocytopenia, run by Assistance Publique - Hôpitaux de Paris at 1 site in France.
Trial summary
Previous studies have shown that increase level of BAFF could promote the settlement of long-lived plasma cells in the spleen of ITP patients treated with anti-CD20. This single-center prospective pilot study, currently in phase IIa, will evaluate the efficacy of a rituximab and belimumab sequential combination… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Immune Thrombocytopenia
- What is being tested?
- Rituximab (Mabthera ®) Belimumab (Benlysta ®)
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 15 participants
- Where
- 1 siteFrance
- Study dates
- 13 Mar 2017to 13 Nov 2019
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age ≥ 18 years, <75 years
- Primary ITP diagnostic defined according to the standard definition criteria (Rodeghiero et al Blood 2008)
- Previous transient response to first-line treatments of corticosteroids and/or IgIV characterized by a rise of platelet levels > 30 G/L with at least a twofold increase from baseline levels followed by a relapse.
- Platelet count ≤ 30,000 /µL at inclusion or <50 G/L if presence of hemorrhagic events or other reason left up to investigator discretion.
- A persistent ITP active and existing for more than 3 months but less than 5 years from diagnosis.
- Normal Bone marrow smear for patients above 60 years of age
Show all 9Show fewer
- Negative pregnancy test results for women of procreation age
- Gammaglobulin level > 7 g/L
- Informed consent
Who cannot join
- Splenectomy
- Previous treatment by Rituximab or any B-cell targeted therapy
- Previous treatment by cyclophosphamide
- No medical treatments of a therapeutic protocol nature within the last 30 days
- Previous anaphylactic shock
- Previous septic shock or severe sepsis
Show all 25Show fewer
- Chronic and ongoing severe infection requiring treatment or hospitalization in the 60 days preceding inclusion.
- Severe acute infection within the last 4 weeks
- Use of parenteral antibiotics within 60 days current use of suppressive therapy for chronic infection such as tuberculosis, pneumocystis, cytomegalovirus, HSZ, herpes zoster, and atypical mycobacteria
- History of primary immunodeficiency, IgG level < 400 mg/dl and/or IgA level < 10 mg/dl
- Have evidence of serious suicide risk including any history of suicidal behavior in the last 6 months and/or any suicidal ideation in the last 2 months or who in the investigator's judgment, pose a significant suicide risk.
- Secondary ITP
- History of recurrent infections
- Neutrophils count < 1,000/mm3 at inclusion
- Positive HIV test and/or hepatitis virus C infection and/or positive hepatitis B virus surface antigen or core antibody (HbsAg or HBcAb)
- Impaired renal function as indicated by a serum creatinine level > 2 mg/dl
- New York Heart Classification III or IV heart disease
- Treatment by antiaggregant/antiplatelet or anti-vitamin K drug
- Previous history of malignancy in the last 5 years other than cutaneous carcinoma
- Previous history of severe psychiatric disorder or previous suicide attempts in the last 6 months or suicidal thoughts in the last 2 months leading up to inclusion
- Unable to comply with study and follow-up procedures due to psychiatric disorders or any other reason
- Alcohol or drug abuse or dependence, either current or within 1year
- Pregnancy or Breast-Feeding
- Live, attenuated vaccinations must be administered at least 30 days before inclusion in study
- History of significant medical illness or clinically significant laboratory abnormality (or planned surgical procedure) which in the opinion of the investigator would interfere with the study procedures and / or assessments or compromise subject safety
Trial locations and contacts
1 site in 1 country.
About this study
Official title: RITUX-PLUS. A Prospective Open Trial to Assess the Efficacy and Safety of a Treatment Combining Rituximab and Belimumab in Adults With Persistent Immune Thrombocytopenia.
Previous studies have shown that increase level of BAFF could promote the settlement of long-lived plasma cells in the spleen of ITP patients treated with anti-CD20. This single-center prospective pilot study, currently in phase IIa, will evaluate the efficacy of a rituximab and belimumab sequential combination treatment. Investigators plan to include 15 patients with persistent ITP over a 24-month inclusion period. Each patient will be followed for 1 year
Read the detailed description
This single-center prospective pilot study, currently in phase IIa, evaluates the efficacy of a rituximab and belimumab sequential combination treatment. Based on the Fleming method, this study scheme includes a single step method.
Eligible patients, having given consent and having been verified for inclusion criteria, will receive two intravenous perfusions of 1 g of Rituximab (Mabthera ®) at W0 and W2 coupled with 100 mg intravenous methylprednisone to avoid potential allergic reactions.
Five belimumab (Benlysta ®) injections will be administered (W0 + 2days, W2 + 2 days, W4, W8, W12) at 10mg/kg doses. The first two injections are administered 2 days after Rituximab perfusions. The adopted experimental scheme was once used to show use of belimumab in systemic lupus erythematosus in accordance with AMM regulation.
This phase II prospective single-center open-trial will be conducted at the National Referral Center for Adult Immune Cytopenia located in the Henri Mondor University Hospital. Investigators plan to include 15 patients with persistent ITP over an 24-month inclusion period. Each patient will be followed for 1 year
- Conditions
- Immune Thrombocytopenia
- Being tested
- Rituximab (Mabthera ®) Belimumab (Benlysta ®)
- Keywords
- ITP
- Medical subject headings
- Purpura, Thrombocytopenic, Idiopathic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Rituximab (Mabthera ®) Belimumab (Benlysta ®)Drug
Rituximab (Mabthera ®): 1g IV at W0 and W2 Belimumab (Benlysta ®) : 10mg/kg IV, W0 + 2days, W2 + 2 days, W4, W8, W12
| Study group | Role | What they receive |
|---|---|---|
| arm 1 | Experimental | Two intravenous perfusions of 1 g of Rituximab (Mabthera ®) at W0 and W2 coupled with 100 mg intravenous methylprednisone to avoid potential allergic reactions.
Five belimumab (Benlysta ®) injections will be administered (W0 + 2days, W2 + 2 days, W4, W8, W12) at 10mg/kg doses. The first two injections are administered 2 days after Rituximab perfusions. The adopted experimental scheme was once used to show use of belimumab in systemic lupus erythematosus in accordance with AMM regulation Receives: Drug: Rituximab (Mabthera ®) Belimumab (Benlysta ®) |
What is being measured
The primary outcome is the main question the study is designed to answer.
The total number of patient responses to treatment, in other words sum of complete responses + responders
A responder (R) to treatment is defined by a patient with a maintained platelet count at >30x109/L (Rodeghiero et al Blood 2008) and a minimum twofold increase from initial platelet levels in the absence of bleeding and/or use of ITP directed therapies between Week 6 and Week 52 of patient follow-up.
A complete response (CR) is defined by a platelet count > 100 x 109/L maintained in the absence of any other ITP directed therapies between Week 6 and Week 52.
A Non-Responder (NR) is a patient with one or all of the following :
- Platelet count less than < 30 x 109/L by the end of study
- Require a rescue therapy (a new course of corticosteroids and/or intravenous immunoglobulin) more than 6 weeks after inclusion.
- Underwent any other treatment for ITP over the study period
Measured: Week 52
Secondary outcomes (7)
Number of patients developing a severe hypogammaglobulinemia (gammaglobulin level < 4 g/dl)
Measured: at weeks 12, 24, 36, and 52
Evolution of gammaglobulin levels
Measured: at weeks 4, 8, 12, 24, 36, and 52
Duration of severe hypogammaglobulinemia in patients with such complication
Measured: Week 24
Variation in gammaglobulin subclass levels throughout the study
Measured: at weeks 0,12, 24, 36, 52
Number of severe infections requiring hospitalization
Measured: at weeks 24, 36 and 52
Platelet Levels
Measured: at weeks 4, 8, 12, 24, 36, and 52
Total number of responders (responders + complete responses)
Measured: at weeks 12,25, and 36
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 May 2017
- Study start13 Mar 2017
- Primary completion13 Nov 2019
- Study completion13 Nov 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Immune ThrombocytopeniaStudies of the same condition, open and under way.
- More trials run by Assistance Publique - Hôpitaux de ParisThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 15 participants (actual)
Sponsor and investigators
- Lead sponsor
- Assistance Publique - Hôpitaux de Paris
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03154385
- Sponsor's protocol ID
- P130408
- Acronym
- RITUX PLUS
- Status last verified
- Feb 2020
- First submitted
- 13 Apr 2017
- Last updated
- 18 Feb 2020
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
Mahevas M, Azzaoui I, Crickx E, Canoui-Poitrine F, Gobert D, Languille L, Limal N, Guillaud C, Croisille L, Jeljeli M, Batteux F, Baloul S, Fain O, Pirenne F, Weill JC, Reynaud CA, Godeau B, Michel M. Efficacy, safety and immunological profile of combining rituximab with belimumab for adults with persistent or chronic immune thrombocytopenia: results from a prospective phase 2b trial. Haematologica. 2021 Sep 1;106(9):2449-2457. doi: 10.3324/haematol.2020.259481.
PubMed 32817288
Study at a glance
From the registry record, last updated by the sponsor on 18 Feb 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- RITUX-PLUS. A Prospective Open Trial to Assess the Efficacy and Safety of a Treatment Combining Rituximab and Belimumab in Adults With Persistent Immune Thrombocytopenia.
- ClinicalTrials.gov ID
- NCT03154385
- Acronym / sponsor ID
- RITUX PLUS / P130408
- Conditions
- Immune Thrombocytopenia
- Keywords
- ITP
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 15 participants (actual)
- Lead sponsor
- Assistance Publique - Hôpitaux de ParisUniversity, hospital or other
- Study start
- 13 Mar 2017 (actual)
- Primary completion
- 13 Nov 2019 (actual)
- Study completion
- 13 Nov 2019 (actual)
- First posted
- 16 May 2017 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Previous studies have shown that increase level of BAFF could promote the settlement of long-lived plasma cells in the spleen of ITP patients treated with anti-CD20. This single-center prospective pilot study, currently in phase IIa, will evaluate the efficacy of a rituximab and belimumab sequential combination treatment. Investigators plan to include 15 patients with persistent ITP over a 24-month inclusion period. Each patient will be followed for 1 year
Detailed description
This single-center prospective pilot study, currently in phase IIa, evaluates the efficacy of a rituximab and belimumab sequential combination treatment. Based on the Fleming method, this study scheme includes a single step method.
Eligible patients, having given consent and having been verified for inclusion criteria, will receive two intravenous perfusions of 1 g of Rituximab (Mabthera ®) at W0 and W2 coupled with 100 mg intravenous methylprednisone to avoid potential allergic reactions.
Five belimumab (Benlysta ®) injections will be administered (W0 + 2days, W2 + 2 days, W4, W8, W12) at 10mg/kg doses. The first two injections are administered 2 days after Rituximab perfusions. The adopted experimental scheme was once used to show use of belimumab in systemic lupus erythematosus in accordance with AMM regulation.
This phase II prospective single-center open-trial will be conducted at the National Referral Center for Adult Immune Cytopenia located in the Henri Mondor University Hospital. Investigators plan to include 15 patients with persistent ITP over an 24-month inclusion period. Each patient will be followed for 1 year
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| arm 1 | Experimental | Drug: Rituximab (Mabthera ®) Belimumab (Benlysta ®)Two intravenous perfusions of 1 g of Rituximab (Mabthera ®) at W0 and W2 coupled with 100 mg intravenous methylprednisone to avoid potential allergic reactions. Five belimumab (Benlysta ®) injections will be administered (W0 + 2days, W2 + 2 days, W4, W8, W12) at 10mg/kg doses. The first two injections are administered 2 days after Rituximab perfusions. The adopted experimental scheme was once used to show use of belimumab in systemic lupus erythematosus in accordance with AMM regulation |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- Age ≥ 18 years, <75 years
- Primary ITP diagnostic defined according to the standard definition criteria (Rodeghiero et al Blood 2008)
- Previous transient response to first-line treatments of corticosteroids and/or IgIV characterized by a rise of platelet levels > 30 G/L with at least a twofold increase from baseline levels followed by a relapse.
- Platelet count ≤ 30,000 /µL at inclusion or <50 G/L if presence of hemorrhagic events or other reason left up to investigator discretion.
- A persistent ITP active and existing for more than 3 months but less than 5 years from diagnosis.
Key exclusion criteria (25 listed)
- Splenectomy
- Previous treatment by Rituximab or any B-cell targeted therapy
- Previous treatment by cyclophosphamide
- No medical treatments of a therapeutic protocol nature within the last 30 days
- Previous anaphylactic shock
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Rituximab (Mabthera ®) Belimumab (Benlysta ®)Rituximab (Mabthera ®): 1g IV at W0 and W2 Belimumab (Benlysta ®) : 10mg/kg IV, W0 + 2days, W2 + 2 days, W4, W8, W12 | Drug | arm 1 |
Primary outcome
The total number of patient responses to treatment, in other words sum of complete responses + responders
Time frame: Week 52
A responder (R) to treatment is defined by a patient with a maintained platelet count at >30x109/L (Rodeghiero et al Blood 2008) and a minimum twofold increase from initial platelet levels in the absence of bleeding and/or use of ITP directed therapies between Week 6 and Week 52 of patient follow-up. A complete response (CR) is defined by a platelet count > 100 x 109/L maintained in the absence of any other ITP directed therapies between Week 6 and Week 52. A Non-Responder (NR) is a patient with one or all of the following : 1. Platelet count less than < 30 x 109/L by the end of study 2. Require a rescue therapy (a new course of corticosteroids and/or intravenous immunoglobulin) more than 6 weeks after inclusion. 3. Underwent any other treatment for ITP over the study period
7 secondary outcomes
Number of patients developing a severe hypogammaglobulinemia (gammaglobulin level < 4 g/dl)
Time frame: at weeks 12, 24, 36, and 52
Evolution of gammaglobulin levels
Time frame: at weeks 4, 8, 12, 24, 36, and 52
Duration of severe hypogammaglobulinemia in patients with such complication
Time frame: Week 24
Variation in gammaglobulin subclass levels throughout the study
Time frame: at weeks 0,12, 24, 36, 52
Number of severe infections requiring hospitalization
Time frame: at weeks 24, 36 and 52
Platelet Levels
Time frame: at weeks 4, 8, 12, 24, 36, and 52
Total number of responders (responders + complete responses)
Time frame: at weeks 12,25, and 36
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Feb 2020.
- Derived from this study: PubMed 32817288Mahevas M, Azzaoui I, Crickx E, Canoui-Poitrine F, Gobert D, Languille L, Limal N, Guillaud C, Croisille L, Jeljeli M, Batteux F, Baloul S, Fain O, Pirenne F, Weill JC, Reynaud CA, Godeau B, Michel M. Efficacy, safety and immunological profile of combining rituximab with belimumab for adults with persistent or chronic immune thrombocytopenia: results from a prospective phase 2b trial. Haematologica. 2021 Sep 1;106(9):2449-2457. doi: 10.3324/haematol.2020.259481.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Rituximab (Mabthera ®) Belimumab (Benlysta ®) in people with Immune Thrombocytopenia, run by Assistance Publique - Hôpitaux de Paris at 1 site in France.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 25 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 18 Feb 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
The total number of patient responses to treatment, in other words sum of complete responses + responders (time frame: Week 52). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03154385, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Feb 2020.