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

Clinical Study on the Treatment of Refractory Immune-related Cytopenia With CD20 Monoclonal Antibody Combined With BTK Inhibitor (BTKi)

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).

Study Overview

• Status: Not yet recruiting
• Conditions: Immune Thrombocytopenia (ITP); BTK Inhibitors; Autoimmune Hemolytic Anemia (AIHA); Anti-CD20 Monoclonal Antibody
• Intervention / Treatment: Drug: Anti-CD20 monoclonal antibody and the BTK inhibitor

• Study Type: Interventional
• Enrollment (Estimated): 30
• Phase: Phase 1

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• 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:

  1. liver function: ALT/AST < 3 times the upper limit of normal;
  2. kidney function: creatinine < 100 μmol/L;
  3. lung function: indoor oxygen saturation ≥ 95%;
  4. 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.

Exclusion Criteria:

• 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:

  1. clinically significant atrial fibrillation (AF),
  2. cardiac conduction block,
  3. myocardial infarction (within 1 year),
  4. congestive heart failure (CHF);
  5. cardiac echocardiography LVEF < 50%;
  6. 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	The early overall response rate 3 months after the start of treatment	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	The sustained remission rate that lasts for 6 months after achieving remission	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	The incidence and severity of therapy related toxic reactions (including infections, bleeding, cardiac toxicity)	Up to three month after therapy

Collaborators and Investigators

• Sponsor: Qi deng

Study record dates

Study Major Dates

• Study Start (Estimated): June 1, 2026
• Primary Completion (Estimated): May 31, 2028
• Study Completion (Estimated): May 31, 2028

Study Registration Dates

• First Submitted: May 1, 2026
• First Submitted That Met QC Criteria: May 1, 2026
• First Posted (Actual): May 7, 2026

Study Record Updates

• Last Update Posted (Actual): May 22, 2026
• Last Update Submitted That Met QC Criteria: May 19, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cytopenia; Pathologic Processes; Autoimmune Diseases; Immune System Diseases; Hemorrhage; Skin Manifestations; Hematologic Diseases; Blood Coagulation Disorders; Hemorrhagic Disorders; Anemia, Hemolytic; Anemia; Blood Platelet Disorders; Thrombotic Microangiopathies; Purpura, Thrombocytopenic; Purpura; Thrombocytopenia; Pathological Conditions, Signs and Symptoms; Signs and Symptoms; Hemic and Lymphatic Diseases; Purpura, Thrombocytopenic, Idiopathic; Anemia, Hemolytic, Autoimmune
• Other Study ID Numbers: 2026-50

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No