RRAIHA01: Single-dose Anti-CD20 Antibody With Bortezomib for Relapsed Refractory Autoimmune Hemolytic Anemia

Sponsor

Peking Union Medical College Hospital (Other)

Overall Status

Recruiting

CT.gov ID

NCT04083014

Collaborator

(none)

Enrollment

Location

Arm

Anticipated Duration (Months)

0.9

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Autoimmune Hemolytic Anemia Autoimmune Hemolytic Anemia and Autoimmune Thrombocytopenia	Drug: combination of a single dose anti-CD20 antibody and bortezomib	Phase 2

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 Design

Study Type:

Interventional

Anticipated Enrollment :

43 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

An Open, One-arm, Prospective Study of a Single Dose Anti-CD20 Monoclonal Antibody Combined With Bortezomib for Treatment of Relapsed Refractory Autoimmune Hemolytic Anemia

Actual Study Start Date :

Aug 20, 2019

Anticipated Primary Completion Date :

Aug 20, 2022

Anticipated Study Completion Date :

Aug 20, 2023

Arms and Interventions

Arm	Intervention/Treatment
Experimental: study group 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.	Drug: combination of a single dose anti-CD20 antibody and bortezomib Relapsed and refractory warm AIHA patients receive treatment of combination of a single dose anti-CD20 antibody and bortezomib twice during three months interval. Other Names: Rituximab Injection Bortezomib for Injection

Arm

Intervention/Treatment

Experimental: study group

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.

Drug: combination of a single dose anti-CD20 antibody and bortezomib

Relapsed and refractory warm AIHA patients receive treatment of combination of a single dose anti-CD20 antibody and bortezomib twice during three months interval.

Other Names:

Rituximab Injection

Bortezomib for Injection

Outcome Measures

Primary Outcome Measures

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

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 80 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Diagnosis of warm autoimmune hemolytic anemia or EVANS syndrome, primary or secondary.
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.
Normal heart function, liver function (total bilirubin < 1.5×ULN, ALT, AST < 3.0 ×ULN), and renal function (serum creatinine < 1.0 ×ULN).
No active infection.
No malignant tumors (except carcinoma in situ).
Patients understand the content of the study, participate the study and sign the informed consent voluntarily.