Eltrombopag with rituximab versus eltrombopag alone for adults with ITP

A Multicenter, Randomized, Open-label Study To Compare The Efficacy And Safety Of Eltrombopag Combining Rituximab With Eltrombopag In Adult ITP Patients

This study tests whether adding a single rituximab infusion to daily eltrombopag helps adults with previously treated ITP who still have low platelets.

Quick facts

• Phase: Phase 4
• Study type: Interventional
• Enrollment: 224 (estimated)
• Ages: 18 Years to 60 Years
• Sex: All
• Sponsor: Institute of Hematology & Blood Diseases Hospital, China (Academic / other)
• Drugs / interventions: rituximab
• Locations: 1 site (Tianjin)
• Trial ID: NCT04518475 on ClinicalTrials.gov

What this trial studies

This multicenter, randomized, open‑label Phase 4 trial in China enrolled 224 adults with previously treated primary ITP and platelet counts under 30×10^9/L, randomizing them 1:1 to eltrombopag alone or eltrombopag plus a single rituximab infusion. All participants started eltrombopag 75 mg orally once daily with dose adjustments based on platelet counts through week 24, and the combination arm received rituximab 375 mg/m2 once within 14 days after enrollment. The primary comparison was efficacy and safety between the two arms, with secondary analyses including response in autoantibody‑positive patients and health‑related quality of life measures. Patients were followed at participating hematology centers for platelet responses and adverse events.

Who should consider this trial

Good fit: Adults aged 18–60 with primary ITP who have not responded to or have relapsed after prior therapies (including post‑splenectomy ≥6 months) and who have platelet counts below 30×10^9/L are the intended candidates.

Not a fit: Patients with recent significant cardiac disease, certain arrhythmias or prolonged QTc, active infections, contraindications to rituximab or eltrombopag, or those outside the 18–60 age range are unlikely to be eligible or to benefit from this regimen.

Why it matters

Potential benefit: If successful, the combination could produce higher or more durable platelet responses than eltrombopag alone, potentially lowering bleeding risk and reducing the need for ongoing therapy.

How similar studies have performed: Eltrombopag and other TPO receptor agonists are well established in ITP and rituximab has produced responses in some patients, and smaller combination or sequential studies have suggested potential added benefit though large randomized confirmations are limited.

Eligibility criteria

Inclusion Criteria:

1. Signed written informed consent
2. Age from 18 to 60 years old
3. Diagnosed with ITP and have a platelet count of \<30 ×10\^9/L on Day 1 (or within 48 hours prior to dosing on Day 1).
4. Patients who have no response or relapsed after splenectomy(at least more than 6 months). Or patients who have not been splenectomised and have either not responded to one or more prior therapies, or who have relapsed prior therapy.
5. Subjects treated with previous therapy(including but not limited to corticosteroid, azathioprine, danazol, cyclosporin A, mycophenolate mofetil) must have been completed prior to randomization, or must not be increasing a dose after enrollment.
6. No pre-existing cardiac disease within the last 3 months. No arrhythmia known to increase the risk of thrombolic events (e.g. atrial fibrillation), or patients with a Corrected QT interval (QTc) \>450msec or QTc \>480 for patients with a Bundle Branch Block.
7. No pre-existing infection within the last 1 months(including but not limited to pulmonary infection)
8. Laboratory tests for coagulation function showed that prothrombin time (PT/INR) and activated partial thromboplastin time (APTT) no exceed normal by more than 20%. No history of clotting disorder, other than ITP.
9. White blood cell count, neutrophil absolute value, hemoglobin, within the reference range, with the following exceptions:

   * Hemoglobin: females and males 10.0 g/dl are eligible for inclusion,
   * Absolute neutrophil count (ANC) ≥1500/µL (1.5×109/L) is required for inclusion
10. The following blood chemistry test result no exceed normal by more than 20%:alanine aminotransferase, aspartate aminotransferase, total bilirubin, creatinine,serum albumin must not be below the lower limit of normal (LLN) by more than 10%.
11. Subject is non-childbearing potential of childbearing potential and use acceptable methods of contraception throughout the study.
12. Subjects fully understand and are able to comply with the requirements of the research protocol and are willing to complete the study as planned.

Exclusion Criteria:

1. Patients with any prior history of arterial or venous thrombosis, and with following risk factors: cancer, Factor V Leiden, ATIII deficiency, antiphospholipid syndrome.
2. Pregnant or lactating women;
3. Subjects is currently receiving treatment with another study medication.
4. Any laboratory or clinical evidence for HIV infection.
5. Any clinical history for hepatitis C infection; chronic hepatitis B infection; or any evidence for active hepatitis at the time of subject screening. Laboratory test shows positive serology for Hepatitis C or Hepatitis B (HB). In addition, if negative for HBsAg but HBcAb positive (regardless of HBsAb status), a HB DNA test will be performed and if positive the subject will be excluded.
6. History of platelet aggregation that prevents reliable measurement of platelet counts.
7. Any clinically relevant abnormality, other than ITP,which in the opinion of the investigator makes the subject unsuitable for participation in the study.

Where this trial is running

Tianjin

• Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College — Tianjin, China (Recruiting)

Study contacts

• Principal investigator: Lei Zhang, M.D., Ph.D — Institute of Hematology & Blood Diseases Hospital, China
• Study coordinator: Lei Zhang

Conditions Primary Immune Thrombocytopenia; immune thrombocytopenia; autoantibody; eltrombopag; rituximab