CD20 Monoclonal Antibody Combined With BTK Inhibitor for the Treatment of Refractory Immune-related Cytopenia

NCT07574073 | Not Yet Recruiting Phase 1

• 1 other identifier: 2026-50
• Study Type: interventional
• Target: 30
• Locations: 0 countries
• Sites: N/A

Brief Summary

This study aims to utilize anti-CD20 monoclonal antibodies to eliminate peripheral B cells and reduce the mechanism of autoantibody production, as well as combine the mechanism of BTK inhibitors (BTKi) blocking the B cell receptor signaling pathway and inhibiting B cell activation and proliferation, for the treatment of refractory immune-related cytopenia. In this study, it includes the salvage treatment of immune thrombocytopenia (ITP) and autoimmune hemolytic anemia (AIHA), expecting to achieve a synergistic and enhancing effect. This study aims to select Zuberitamab, a human-mouse chimeric anti-CD20 monoclonal antibody, and the BTKi Orelabrutinib as combination therapy options. The clinical efficacy of the Zuberitamab-Orelabrutinib combination therapy (overall response rate, duration of sustained remission) will be evaluated, along with its safety profile (including infections, bleeding, cardiac toxicity), to provide a theoretical basis for their combined use in treating refractory immune-related thrombocytopenia (ITP and AIHA).

Conditions

Refractory Immune-related Cytopenia; Anti-CD20 Monoclonal Antibody; BTK Inhibitors

Outcome Measures

Primary Outcomes (1)

• Evaluate the Median overall response rate at 6 months of anti-CD20 monoclonal antibody and BTKi combination therapy in refractory immune-related cytopenia

  Median overall response rate at 6 months after treatment initiation

  Six month after treatment initiation

Secondary Outcomes (3)

• Evaluate the early overall response rate 3 months after the start of anti-CD20 monoclonal antibody and BTKi combination therapy in refractory immune-related cytopenia

  Three month after therapy

• Evaluate the sustained remission rate that lasts for 6 months after achieving remission following anti-CD20 monoclonal antibody and BTKi combination therapy in refractory immune-related cytopenia

  Six month after achieving remission

• Evaluate the Incidence of Treatment-Emergent Adverse Events (Safety and Tolerability) of anti-CD20 monoclonal antibody and BTKi combination therapy in refractory immune-related cytopenia

  Up to three month after therapy

Study Arms (1)

Zuberitamab-Orelabrutinib combination therapy

EXPERIMENTAL

This study is designed as a non-randomized, single-arm, open-label clinical trial. Patients with refractory immune-related cytopenia, including immune thrombocytopenia (ITP) and autoimmune hemolytic anemia (AIHA), are intended for enrollment. The treatment regimen and schedule are as follows: anti-CD20 monoclonal antibody (Zuberitamab): 100 mg per dose on Days 1, 8, 15, and 22; BTK inhibitor (Orelabrutinib): 50 mg once daily (qd) from Day 1 to Day 90.

Drug: Anti-CD20 monoclonal antibody and the BTK inhibitor

Interventions

Anti-CD20 monoclonal antibody and the BTK inhibitor DRUG

This is a novel combination regimen of anti-CD20 monoclonal antibody plus BTKi, specifically designed for patients with refractory immune-related cytopenia.

Zuberitamab-Orelabrutinib combination therapy

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Diagnosed with refractory immune-related cytopenia, including immune thrombocytopenic purpura (ITP) and autoimmune hemolytic anemia (AIHA);
• Age ranging from 18 to 80 years old (inclusive of 18 and 80);
• Expected survival time \> 12 months;
• Good function of major organs:
• liver function: ALT/AST \< 3 times the upper limit of normal;
• kidney function: creatinine \< 100 μmol/L;
• lung function: indoor oxygen saturation ≥ 95%;
• heart function: left ventricular ejection fraction (LVEF) ≥ 50%;
• Peripheral superficial venous blood flow is unobstructed, capable of meeting the requirements for intravenous infusion;
• Karnofsky score ≥ 60, ECOG ≤ 2 points.

You may not qualify if:

• Women who are pregnant (with positive urine/blood pregnancy test results) or breastfeeding;
• Those who have severe underlying heart diseases when participating in this study, including:
• clinically significant atrial fibrillation (AF),
• cardiac conduction block,
• myocardial infarction (within 1 year),
• congestive heart failure (CHF);
• cardiac echocardiography LVEF \< 50%;
• New York Heart Association (NYHA) cardiac function classification of III-IV grade;
• Those with active bleeding or bleeding tendencies, and those who need to take anticoagulant drugs;
• Those with organ dysfunction or uncontrollable coexisting diseases;
• History of malignant tumors;
• Those with active chronic hepatitis B or active hepatitis C;
• Known history of human immunodeficiency virus (HIV) infection and/or acquired immunodeficiency syndrome;
• Those with uncontrollable infectious diseases;
• As determined by the investigator, other unsuitable conditions exist.

Sponsors & Collaborators

• Qi deng: lead

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Chief Physician

Study Record Dates

• First Submitted: May 1, 2026
• First Posted: May 7, 2026
• Study Start (Estimated): June 1, 2026
• Primary Completion (Estimated): May 31, 2028
• Study Completion (Estimated): May 31, 2028
• Last Updated: May 7, 2026

Record last verified: 2026-05