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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04083014
Recruitment Status : Recruiting
First Posted : September 10, 2019
Last Update Posted : September 10, 2019
Sponsor:
Information provided by (Responsible Party):
Chen Miao, 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.

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 43 participants
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 : August 20, 2019
Estimated Primary Completion Date : August 20, 2022
Estimated Study Completion Date : August 20, 2023


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




Primary Outcome Measures :
  1. response time [ Time Frame: two years ]
    days hemoglobin increasing more than 20g/L

  2. overall response [ Time Frame: two years ]
    total of complete response and partial response

  3. complete response [ Time Frame: two years ]
    rate of achieving complete response

  4. relapse rate [ Time Frame: two years ]
    relapse rate of responders


Secondary Outcome Measures :
  1. relapse free survival [ Time Frame: two years ]
    time duration of responders from first treatment to recurrence of decompensated hemolysis

  2. overall survival [ Time Frame: two years ]
    time from first treatment to death of any causes

  3. side effects [ Time Frame: two years ]
    side effects due to the combination of anti-CD20 antibody and bortezomib



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04083014


Contacts
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Contact: Miao Chen +86 13520112578 chenm@pumch.cn

Locations
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China, Beijing
Peking Union Medical College Hospital Recruiting
Beijing, Beijing, China, 100730
Contact: Miao Chen    +86 13520112578    chenm@pumch.cn   
Contact: Bing Han    +86 69155028    hanbingpumch@163.com   
Sponsors and Collaborators
Peking Union Medical College Hospital
Investigators
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Study Director: Bing Han Peking Union Medical College Hospital

Publications:

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Responsible Party: Chen Miao, associate professor, Peking Union Medical College Hospital
ClinicalTrials.gov Identifier: NCT04083014    
Other Study ID Numbers: HS-2053
First Posted: September 10, 2019    Key Record Dates
Last Update Posted: September 10, 2019
Last Verified: September 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Patients age,gender,diagnosis,treatment details, efficiency and survival.
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Informed Consent Form (ICF)
Clinical Study Report (CSR)
Analytic Code
Time Frame: The data will become available 6 months after the publication of the study and for 2 years.
Access Criteria: get permission from the researchers.

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Chen Miao, Peking Union Medical College Hospital:
warm autoimmune hemolytic anemia
relapsed
refractory
EVANS syndrome
anti-CD20 monoclonal antibody
bortezomib
Additional relevant MeSH terms:
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Thrombocytopenia
Immune System Diseases
Anemia
Anemia, Hemolytic
Anemia, Hemolytic, Autoimmune
Purpura, Thrombocytopenic, Idiopathic
Hemolysis
Hematologic Diseases
Blood Platelet Disorders
Pathologic Processes
Autoimmune Diseases
Purpura, Thrombocytopenic
Purpura
Blood Coagulation Disorders
Thrombotic Microangiopathies
Hemorrhagic Disorders
Hemorrhage
Skin Manifestations
Signs and Symptoms
Bortezomib
Antibodies
Immunoglobulins
Antibodies, Monoclonal
Immunologic Factors
Physiological Effects of Drugs
Antineoplastic Agents