Single-dose Anti-CD20 Antibody With Bortezomib for Relapsed Refractory Autoimmune Hemolytic Anemia

Phase 2

Completed

• Conditions: Autoimmune Hemolytic Anemia; Autoimmune Hemolytic Anemia and Autoimmune Thrombocytopenia
• Interventions: Drug: combination of a single dose anti-CD20 antibody and bortezomib

• Registration Number: NCT04083014
• Lead Sponsor: Peking Union Medical College Hospital

Brief Summary

Patients of relapsed and refractory warm autoimmune hemolytic anemia or EVANS syndrome aged 18 to 80 will be included in this study. The treatment regimen is a single dose anti-CD20 antibody (500mg) combined with bortezomib (1.3mg/m2 twice a week for two weeks). The treatment course would be repeated three months later.

Detailed Description

Glucocorticoids are the first-line treatment of warm AIHA. The overall response is 70-90%, but 10% to 20% patients are refractory to GCs and more than 50% patients will relapse after GCs tapering or cessation.

Anti-CD20 monoclonal antibody is the preferred second-line treatment for relapsed refractory wAIHA. Anti-CD20 antibody 375 mg/m2, once a week, four times, is the standard treatment regimen. Low dose anti-CD20 antibody, 100mg once a week, four times, also showed similar response rate. However, the use of four times of intravenous infusion is trouble. So the investigators intend to explore the efficiency of the singe dose of 500mg anti-CD20 antibody.

Anti-CD20 antibody takes median 6-8 weeks to response and only about 50% patients achieving long-term response. Plasma cells produce antibodies and long-lived plasma cells in bone marrow and spleen continuously work. Bortezomib is a proteasome inhibitor and targets plasma cells. Bortezomib has become a first-line treatment for clonal plasma cell diseases (such as multiple myeloma, systemic amyloidosis, POEMS syndrome, etc.). Bortezomib can also induce reactive plasma cell apoptosis and has a variety of immunomodulatory effects. The investigators try to combine bortezomib with anti-CD20 antibody, which may play a synergistic role and improve the efficacy.

Patients of relapsed and refractory warm autoimmune hemolytic anemia or EVANS syndrome will receive a single dose anti-CD20 antibody (500mg) and bortezomib (1.3mg/m2 twice a week for two weeks) twice for three months interval.

Study Timeline

• Study Start: 2019-08-20
• Study First Submitted: 2019-08-31
• Study First Submitted QC: 2019-09-05
• Study First Posted: 2019-09-10
• Primary Completion: 2024-03-01
• Study Completion: 2024-03-20
• Status Verified: 2024-04
• Last Update Submitted: 2024-04-25
• Last Update Posted: 2024-04-26

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 33

Inclusion Criteria

1. Diagnosis of warm autoimmune hemolytic anemia or EVANS syndrome, primary or secondary.
2. Patients refractory to glucocorticoids (HGB increase less than 20g/L after three weeks full dose glucocorticoids treatment). Or patients relapse after at least one course of glucocorticoids therapy (HGB < 110g/L in female and HGB < 120g/L in male). Or glucocorticoids dependence (prednisone maintenance dose > 10mg a day). Or glucocorticoids intolerance.
3. Normal heart function, liver function (total bilirubin < 1.5×ULN, ALT, AST < 3.0 ×ULN), and renal function (serum creatinine < 1.0 ×ULN).
4. No active infection.
5. No malignant tumors (except carcinoma in situ).
6. Patients understand the content of the study, participate the study and sign the informed consent voluntarily.

Exclusion Criteria

1. Patients with malignant tumors (excluding carcinoma in situ);
2. With uncontrollable infections or other serious diseases;
3. Active hepatitis B, serume HBV-DNA > 104copies/ml;
4. Women during pregnancy or lactation;
5. Not strict contraception;
6. Psychiatric patients and those with severe mental illness.
7. Other conditions that researchers consider inappropriate to join the study.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
study group	combination of a single dose anti-CD20 antibody and bortezomib	The treatment regimen is a single dose anti-CD20 antibody injection (500mg iv drip，day0) combined with bortezomib injection (1.3mg/m2 subcutaneous injection，twice a week for two weeks，day1，4，8，11). The treatment course will be repeated three months later.

Primary Outcome Measures

Name	Time	Method
response time	two years	days hemoglobin increasing more than 20g/L
overall response	two years	total of complete response and partial response
complete response	two years	rate of achieving complete response
relapse rate	two years	relapse rate of responders

Secondary Outcome Measures

Name	Time	Method
relapse free survival	two years	time duration of responders from first treatment to recurrence of decompensated hemolysis
overall survival	two years	time from first treatment to death of any causes
side effects	two years	side effects due to the combination of anti-CD20 antibody and bortezomib

Trial Locations

Locations (1)

Peking Union Medical College Hospital; 🇨🇳 Beijing, Beijing, China