Dose-Dense Rituximab for ITP

(NYMC207 Trial)

Overseen By Lauren Harrison, MSN

Age: < 65

Sex: Any

Trial Phase: Phase 1

Sponsor: New York Medical College

Must not be taking: Thrombopoetic agonists

Disqualifiers: Allergy to rituximab, Hepatitis B, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 5

Duration: 3-4 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new method of administering Rituximab, a type of immunotherapy, to treat newly diagnosed acute immune thrombocytopenic purpura (ITP). In this condition, the immune system destroys platelets needed for clotting. Researchers aim to determine if more frequent doses of Rituximab can reduce relapse rates. This trial may suit patients aged 1 to 21 who have just been diagnosed with ITP, particularly those with a platelet count below a specific level and certain risk factors like moderate to severe bleeding. Participants will receive the medication in five doses over three weeks. As a Phase 1 trial, the research focuses on understanding how the treatment works in people.

Will I have to stop taking my current medications?

The trial requires that you have not received any treatment for ITP before starting the study and that you do not take certain medications like systemic steroids above a specific dose or thrombopoetic agonists. If you are on these medications, you may need to stop them to participate.

Is there any evidence suggesting that this treatment is likely to be safe for humans?

Research has shown that rituximab, a treatment under study for immune thrombocytopenia (ITP), has been used safely in many patients. In one study with 248 adults with ITP, rituximab was generally well-tolerated. Some patients experienced side effects like flu-like symptoms or mild infections, but these were not severe for most.

Other studies also support rituximab's safety, demonstrating its effectiveness and safety for treating ITP. The FDA has already approved rituximab for other conditions, indicating its well-established safety profile. However, since this study tests a new dosing schedule, monitoring for any new side effects is crucial. Overall, rituximab has a history of safety for many, although individual experiences may vary. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for ITP?

Unlike the standard treatments for Immune Thrombocytopenic Purpura (ITP), which often include corticosteroids and intravenous immunoglobulin (IVIG), this study uses a dose-dense administration of rituximab. Rituximab targets the CD20 protein on B cells, potentially offering a more direct and potent mechanism to reduce the production of antibodies that destroy platelets. Researchers are excited because this approach could lead to faster and more sustained platelet recovery, reducing the need for frequent and ongoing treatments.

What evidence suggests that dose-dense Rituximab might be an effective treatment for ITP?

Research has shown that rituximab can help people with immune thrombocytopenia (ITP). Studies have found that up to 60% of patients with ITP respond to this treatment. In one study, patients who responded had a 72% chance of avoiding relapse for a year. Another study found that these patients remained relapse-free for an average of 29 months. This suggests that rituximab might help maintain stable platelet levels for a long time after treatment. Participants in this trial will receive a dose-dense administration of rituximab, with five total doses given on specific days. ^{6 7 8 9 10}

Who Is on the Research Team?

Jordan Milner, MD

Principal Investigator

New York Medical College

Are You a Good Fit for This Trial?

This trial is for young people (1-21 years old) with a new diagnosis of acute immune thrombocytopenic purpura (ITP), who are at high risk due to factors like being older than 10, severe bleeding, or specific antibody presence. They must have low platelet counts and good kidney and liver function. Pregnant or breastfeeding females, those with certain infections or previous ITP treatments, can't participate.

Inclusion Criteria

My kidney function is good based on tests.

I can do most of my daily activities by myself.

I have not received any treatment for ITP before.

Exclusion Criteria

I am a woman able to have children and have a negative pregnancy test.

You have had a severe allergic reaction to rituximab in the past.

I am not pregnant.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive a dose dense administration of rituximab on Days: 0, 2, 7 (± 2 days), 14 (± 2 days), and 21 (± 2 days); Dose: 375 mg/m2

3-4 weeks

5 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, including assessment of relapse rate and quality of life

1 year

What Are the Treatments Tested in This Trial?

Interventions

• Rituximab

Trial Overview The study tests whether giving Rituximab more frequently ('dose dense') helps newly diagnosed high-risk ITP patients better than standard approaches. It also looks at how long patients stay in remission after this treatment and assesses their quality of life using the KIT questionnaire.

How Is the Trial Designed?

Group I: rituximab Experimental Treatment 1 Intervention

All patients enrolled will receive the dose dense administration of rituximab. Five total doses will be administered on Days: 0, 2, 7 (± 2 days), 14 (± 2 days), and 21 (± 2 days); Dose: 375 mg/m2

Rituximab is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Rituxan for:

• Non-Hodgkin's lymphoma
• Chronic lymphocytic leukemia
• Rheumatoid arthritis
• Granulomatosis with polyangiitis
• Microscopic polyangiitis

Approved in European Union as MabThera for:

• Non-Hodgkin's lymphoma
• Chronic lymphocytic leukemia
• Rheumatoid arthritis
• Granulomatosis with polyangiitis
• Microscopic polyangiitis

Approved in Canada as Rituxan for:

• Non-Hodgkin's lymphoma
• Chronic lymphocytic leukemia
• Rheumatoid arthritis
• Granulomatosis with polyangiitis
• Microscopic polyangiitis

Who Is Running the Clinical Trial?

New York Medical College

Lead Sponsor

Trials

73

Recruited

8,700+

Published Research Related to This Trial

In a study of 26 patients with refractory idiopathic thrombocytopenic purpura (ITP), lower dose rituximab (100 mg per week for four weeks) resulted in a complete response in 23.1% of patients and a response in 38.5%, indicating its effectiveness as a treatment option.

The treatment was found to be safe, with no severe adverse effects reported, and it led to significant decreases in certain B cell populations, suggesting a mechanism of action that may involve the modulation of immune responses in ITP.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Efficacy of lower dose rituximab therapy for idiopathic thrombocytopenic purpura.]. Sui, T., Xue, F., Zhao, HF., et al.[2018]

In a study of 90 children with primary immune thrombocytopenia (ITP), a single-dose rituximab regimen (375 mg/m2) was found to be as effective and safe as a 4-dose regimen (100 mg weekly) in treating the condition, with no significant differences in overall response rates.

The single-dose regimen allowed for a quicker response time and resulted in fewer hospitalizations and shorter hospital stays, making it a more economical and convenient option for second-line treatment in children with ITP.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Comparison of the efficacy and safety of 2 low-dose rituximab regimens in the second-line treatment of primary immune thrombocytopenia in children]. Zhu, XJ., Ma, JY., Chen, ZP., et al.[2022]

In a study of 107 adults with immune thrombocytopenia (ITP), rituximab biosimilars showed a promising overall response rate of 63.5%, which was higher than the 53.5% response rate of matched controls receiving the reference product, although this difference was not statistically significant (p=0.13).

Specifically, Rixathon™ demonstrated a significantly better response rate of 76.5% compared to 51.5% in its matched control group (p=0.01), indicating that rituximab biosimilars can be effective for treating ITP, with a safety profile similar to the reference product.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of two rituximab biosimilars for treating immune thrombocytopenia: a reference-product matched study. Mageau, A., Bonnotte, B., Ebbo, M., et al.[2023]

A combination of high-dose dexamethasone and low-dose rituximab resulted in a 100% overall response rate in 18 adults with newly diagnosed immune thrombocytopenia (ITP) after 28 days, indicating high efficacy as a first-line treatment.

The treatment was well tolerated, with only a low incidence of adverse effects (11.1%), and showed sustained responses in 83.3% of patients after 6 months and 61.5% after 12 months, suggesting it is a safe and effective option for managing ITP.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical Efficacy and Safety of High-Dose Dexamethasone Plus Low-Dose Rituximab as First-Line Therapy in Newly Diagnosed Primary Immune Thrombocytopenia. Zhou, H., Liu, L., Shu, X., et al.[2020]

In a study of 21 patients with chronic ITP, low-dose Rituximab (100 mg/m2 weekly for 4 doses) showed an overall response rate of 47.6%, with a complete response rate of 33.3%, demonstrating its efficacy as a treatment option in resource-limited settings.

The use of low-dose Rituximab not only proved effective but also cost-effective, as it required significantly lower doses than conventional treatments and could be administered in a day care setting without major adverse events, reducing the need for inpatient care.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Low Dose Rituximab in Chronic ITP: Still an Option in Resource Limited Settings. Kapoor, R., Kumar, R., Mahapatra, M., et al.[2020]

In a randomized controlled trial involving patients with corticosteroid-resistant or relapsed primary immune thrombocytopenia (ITP), both low-dose rituximab (LD-RTX) and single-dose rituximab (S-RTX) showed comparable efficacy, with overall response rates of 64.3% and 67.4%, respectively.

The single-dose regimen (S-RTX) not only maintained similar effectiveness but also improved patients' quality of life and reduced the need for physician visits, making it a more convenient and cost-effective treatment option compared to the low-dose regimen.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Single-dose versus low-dose rituximab in corticosteroid-resistant or relapsed ITP: A multicenter, randomized, controlled study. Ni, X., Li, D., Yuan, C., et al.[2022]

The combination of dexamethasone and rituximab significantly improves treatment outcomes for adults with primary immune thrombocytopenia (ITP), showing better overall response and complete response rates compared to dexamethasone alone, based on a meta-analysis of 11 randomized controlled trials.

This combination therapy does not increase the risk of serious adverse effects, indicating it is a safe option for enhancing long-term treatment responses in ITP patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and Safety of the Combination Treatment of Rituximab and Dexamethasone for Adults with Primary Immune Thrombocytopenia (ITP): A Meta-Analysis. Wang, J., Li, Y., Wang, C., et al.[2020]

In a study of 48 adults with symptomatic immune thrombocytopenia (ITP), low-dose rituximab (100 mg weekly for 4 weeks) achieved an overall response rate of 60.5%, with a complete response rate of 39.5%.

While low-dose rituximab was effective, the long-term effects were moderate, with a 12-month relapse-free survival rate of 61% and a 24-month rate of 45%, indicating that further studies comparing it to standard doses are needed.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Low-dose rituximab in adult patients with primary immune thrombocytopenia. Zaja, F., Vianelli, N., Volpetti, S., et al.[2015]

In a study of 122 patients with chronic idiopathic thrombocytopenic purpura (ITP), a fixed-dose schedule of rituximab (two doses of 1000 mg) resulted in an overall response rate of 44% at week 8, indicating its potential effectiveness in increasing platelet counts.

The treatment was well tolerated with no significant safety concerns, and while it did not meet the primary endpoint of a 50% response rate, its efficacy was comparable to the standard four-dose rituximab regimen for ITP.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A multi-centre, single-arm, open-label study evaluating the safety and efficacy of fixed dose rituximab in patients with refractory, relapsed or chronic idiopathic thrombocytopenic purpura (R-ITP1000 study). Tran, H., Brighton, T., Grigg, A., et al.[2015]

In a retrospective study of 66 patients with immune thrombocytopenia (ITP) treated with rituximab, the overall response rate was 51.72% by day 30, indicating that rituximab is an effective second-line therapy for ITP.

The treatment was found to be safe, with infusion-related reactions being the most common adverse event, and a cumulative relapse rate of 56.57% at 5 years, suggesting that while effective, some patients may experience a return of symptoms over time.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real-world Experience of Rituximab in Immune Thrombocytopenia. Mishra, K., Kumar, S., Jandial, A., et al.[2022]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT04323748

Dose Dense Rituximab for High Risk Newly Diagnosed ... The purpose of this study is to determine if a dose dense administration of Rituximab in newly diagnosed acute immune thrombocytopenic purpura (ITP) and ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6545833/

Rituximab in the treatment of immune thrombocytopenia The use of rituximab for the treatment of immune thrombocytopenia was greeted enthusiastically: it led to up to 60% response rates.

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4349285/

Multi-center randomized open label phase II trial on three ... Overall, responding patients showed a 72% RFS at one year and 58% at two years, and a median relapse-free survival of 29 months; comparisons between arms are, ...

4. ohsu.edu ohsu.edu/sites/default/files/2024-02/OHSU%20HS-MRxM-Rituximab-IV%20%28E%29-01-24.pdf

Rituximab: Rituxan®, Truxima®, Ruxience™, Riabni™ Rituximab efficacy and safety in adult splenectomy candidates with chronic immune thrombocytopenic purpura: results of a prospective multicenter phase 2 study.

5. ashpublications.org ashpublications.org/blood/article/128/12/1547/73115/How-I-treat-refractory-immune-thrombocytopenia

How I treat refractory immune thrombocytopenia | Blood The optimal dose of rituximab for ITP treatment has not been established. We use 375 mg/m2 once per week × 4 weeks, but lower doses may be effective (Table 2).

6. ascopubs.org ascopubs.org/doi/10.1200/JCO.2024.42.16_suppl.e23256

Outcomes of rituximab as treatment for immune ... In this study, we explore the rate and duration of response to Rituximab as a second-line agent for ITP. We also analyze relapse rates and response to ...

7. tandfonline.com tandfonline.com/doi/full/10.1080/09537104.2023.2200848

Efficacy and safety of two rituximab biosimilars for treating ... Rituximab biosimilars seemed safe and effective for ITP treatment. Plain Language Summary. What is the context? Immune thrombocytopenia (ITP) is ...

8. clinicaltrials.gov clinicaltrials.gov/study/NCT01525836

NCT01525836 | rhTPO Combining Rituximab Versus Low- ... Adverse events are also recorded throughout the study. In order to report the efficacy and safety of the combination therapy compared to conventional rituximab ...

9. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9272691/

Efficacy and safety of rituximab as second-line therapy in ... Rituximab efficacy and safety in adult splenectomy candidates with chronic immune thrombocytopenic purpura: results of a prospective multicenter phase 2 study.

10. ashpublications.org ashpublications.org/blood/article/124/22/3228/33376/Safety-and-efficacy-of-rituximab-in-adult-immune

Safety and efficacy of rituximab in adult immune ... We conducted a prospective multicenter registry of 248 adult patients with immune thrombocytopenia (ITP) treated with rituximab to assess safety.