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

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

Sponsors

Lead Sponsor: Peking Union Medical College Hospital

Source 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.

Overall Status Recruiting
Start Date August 20, 2019
Completion Date August 20, 2023
Primary Completion Date August 20, 2022
Phase Phase 2
Study Type Interventional
Primary Outcome
Measure Time Frame
response time two years
overall response two years
complete response two years
relapse rate two years
Secondary Outcome
Measure Time Frame
relapse free survival two years
overall survival two years
side effects two years
Enrollment 43
Condition
Intervention

Intervention Type: Drug

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

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

Arm Group Label: study group

Eligibility

Criteria:

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.

Gender: All

Minimum Age: 18 Years

Maximum Age: 80 Years

Healthy Volunteers: No

Overall Official
Last Name Role Affiliation
Bing Han Study Director Peking Union Medical College Hospital
Overall Contact

Last Name: Miao Chen

Phone: +86 13520112578

Email: [email protected]

Location
Facility: Status: Contact: Contact Backup: Peking Union Medical College Hospital Miao Chen +86 13520112578 [email protected]
Location Countries

China

Verification Date

September 2019

Responsible Party

Type: Principal Investigator

Investigator Affiliation: Peking Union Medical College Hospital

Investigator Full Name: Chen Miao

Investigator Title: associate professor

Keywords
Has Expanded Access No
Condition Browse
Number Of Arms 1
Arm Group

Label: study group

Type: Experimental

Description: 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.

Acronym RRAIHA01
Patient Data Yes
Study Design Info

Allocation: N/A

Intervention Model: Single Group Assignment

Primary Purpose: Treatment

Masking: None (Open Label)

Source: ClinicalTrials.gov