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

20 Participants Needed

Trial Summary

What is the purpose of this trial?

The purpose of this study is to determine if a dose dense administration of Rituximab in newly diagnosed acute immune thrombocytopenic purpura (ITP) and determine relapse rate following this treatment. Correlative studies will be performed as outlined in the appendices. Quality of Life will be measured using the KIT as outlined in the protocol.

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.

What data supports the effectiveness of the drug Rituximab for treating ITP?

Research shows that Rituximab is effective as a second-line treatment for ITP, with studies indicating a good overall response rate and sustained response over time. Additionally, combining Rituximab with dexamethasone has been shown to improve long-term outcomes without increasing adverse effects. ^{1 2 3 4 5}

Is Rituximab safe for treating ITP?

Rituximab and its biosimilars, used for treating immune thrombocytopenia (ITP), have been shown to be generally safe in humans. Common side effects include infusion-related reactions, but no major adverse events were reported in studies, even with lower doses. ^{1 3 4 5 6}

How is dose-dense Rituximab different from other drugs for ITP?

Dose-dense Rituximab for ITP involves giving the drug more frequently or at higher doses than standard regimens, which may lead to a quicker or more robust response. This approach is different from typical treatments that use lower doses or less frequent administration, potentially offering a new option for patients who do not respond well to standard therapies. ^{4 7 8 9 10}

Research Team

Jordan Milner, MD

Principal Investigator

New York Medical College

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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 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]

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]

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]

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 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 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 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]

References

1. India pubmed.ncbi.nlm.nih.gov

Real-world Experience of Rituximab in Immune Thrombocytopenia. [2022]

2. United States 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. [2020]

3. India pubmed.ncbi.nlm.nih.gov

Low Dose Rituximab in Chronic ITP: Still an Option in Resource Limited Settings. [2020]

4. United States pubmed.ncbi.nlm.nih.gov

Single-dose versus low-dose rituximab in corticosteroid-resistant or relapsed ITP: A multicenter, randomized, controlled study. [2022]

5. England pubmed.ncbi.nlm.nih.gov

Efficacy and safety of two rituximab biosimilars for treating immune thrombocytopenia: a reference-product matched study. [2023]

6. China pubmed.ncbi.nlm.nih.gov

[Efficacy of lower dose rituximab therapy for idiopathic thrombocytopenic purpura.]. [2018]

7. India 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. [2020]

8. England 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). [2015]

9. China 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]. [2022]

10. England pubmed.ncbi.nlm.nih.gov

Low-dose rituximab in adult patients with primary immune thrombocytopenia. [2015]