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

NCT04083014 | Completed Phase 2

• 1 other identifier: HS-2053
• Study Type: interventional
• Target: 33
• Locations: 1 country
• Sites: 1

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.

Conditions

Autoimmune Hemolytic Anemia; Autoimmune Hemolytic Anemia and Autoimmune Thrombocytopenia

Keywords

warm autoimmune hemolytic anemia; relapsed; refractory; EVANS syndrome; anti-CD20 monoclonal antibody; bortezomib

Outcome Measures

Primary Outcomes (4)

• response time

  days hemoglobin increasing more than 20g/L

  two years

• overall response

  total of complete response and partial response

  two years

• complete response

  rate of achieving complete response

  two years

• relapse rate

  relapse rate of responders

  two years

Secondary Outcomes (3)

• relapse free survival

  two years

• overall survival

  two years

• side effects

  two years

Study Arms (1)

study group

EXPERIMENTAL

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

Interventions

combination of a single dose anti-CD20 antibody and bortezomib DRUG

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

Also known as: Rituximab Injection, Bortezomib for Injection

study group

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

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

Sponsors & Collaborators

• Peking Union Medical College Hospital: lead

Study Sites (1)

Peking Union Medical College Hospital

Beijing, Beijing Municipality, 100730, China

Location

Related Publications (13)

• Lechner K, Jager U. How I treat autoimmune hemolytic anemias in adults. Blood. 2010 Sep 16;116(11):1831-8. doi: 10.1182/blood-2010-03-259325. Epub 2010 Jun 14.

  PMID: 20548093 BACKGROUND

• Group, Chinese Society of Hematology, Chinese Medical Association. [Chinese expert consensus on the diagnosis and treatment of autoimmune hemolytic anemia (2017) Red Blood Cell Disease (Anemia)]. Zhonghua Xue Ye Xue Za Zhi. 2017 Apr 14;38(4):265-267. doi: 10.3760/cma.j.issn.0253-2727.2017.04.001. No abstract available. Chinese.

  PMID: 28468084 BACKGROUND

• Hill A, Hill QA. Autoimmune hemolytic anemia. Hematology Am Soc Hematol Educ Program. 2018 Nov 30;2018(1):382-389. doi: 10.1182/asheducation-2018.1.382.

  PMID: 30504336 BACKGROUND

• Perry DK, Burns JM, Pollinger HS, Amiot BP, Gloor JM, Gores GJ, Stegall MD. Proteasome inhibition causes apoptosis of normal human plasma cells preventing alloantibody production. Am J Transplant. 2009 Jan;9(1):201-9. doi: 10.1111/j.1600-6143.2008.02461.x. Epub 2008 Oct 31.

  PMID: 18976291 BACKGROUND

• Palombella VJ, Rando OJ, Goldberg AL, Maniatis T. The ubiquitin-proteasome pathway is required for processing the NF-kappa B1 precursor protein and the activation of NF-kappa B. Cell. 1994 Sep 9;78(5):773-85. doi: 10.1016/s0092-8674(94)90482-0.

  PMID: 8087845 BACKGROUND

• Berges C, Haberstock H, Fuchs D, Miltz M, Sadeghi M, Opelz G, Daniel V, Naujokat C. Proteasome inhibition suppresses essential immune functions of human CD4+ T cells. Immunology. 2008 Jun;124(2):234-46. doi: 10.1111/j.1365-2567.2007.02761.x. Epub 2008 Jan 23.

  PMID: 18217957 BACKGROUND

• Goldberg AL, Cascio P, Saric T, Rock KL. The importance of the proteasome and subsequent proteolytic steps in the generation of antigenic peptides. Mol Immunol. 2002 Oct;39(3-4):147-64. doi: 10.1016/s0161-5890(02)00098-6.

  PMID: 12200047 BACKGROUND

• Ratnasingam S, Walker PA, Tran H, Kaplan ZS, McFadyen JD, Tran H, Teh TC, Fleming S, Catalano JV, Chunilal SD, Johnston A, Opat SS, Shortt J. Bortezomib-based antibody depletion for refractory autoimmune hematological diseases. Blood Adv. 2016 Nov 22;1(1):31-35. doi: 10.1182/bloodadvances.2016001412. eCollection 2016 Nov 29.

  PMID: 29296693 BACKGROUND

• Muhsen IN, Alahmari A, Alnahedh M, Alkhudair NA, Samarkandi H, El Fakih R. Bortezomib for immune thrombocytopenia and autoimmune hemolytic anemia. Hematol Oncol Stem Cell Ther. 2020 Dec;13(4):251-254. doi: 10.1016/j.hemonc.2019.05.006. Epub 2019 Jun 10. No abstract available.

  PMID: 31202670 BACKGROUND

• Reynaud Q, Durieu I, Dutertre M, Ledochowski S, Durupt S, Michallet AS, Vital-Durand D, Lega JC. Efficacy and safety of rituximab in auto-immune hemolytic anemia: A meta-analysis of 21 studies. Autoimmun Rev. 2015 Apr;14(4):304-13. doi: 10.1016/j.autrev.2014.11.014. Epub 2014 Dec 9.

  PMID: 25497766 BACKGROUND

• Danchaivijitr P, Yared J, Rapoport AP. Successful treatment of IgG and complement-mediated autoimmune hemolytic anemia with bortezomib and low-dose cyclophosphamide. Am J Hematol. 2011 Mar;86(3):331-2. doi: 10.1002/ajh.21950. Epub 2011 Jan 26. No abstract available.

  PMID: 21271614 BACKGROUND

• Hosoba S, Jaye DL, Cohen C, Roback JD, Waller EK. Successful treatment of severe immune hemolytic anemia after allogeneic stem cell transplantation with bortezomib: report of a case and review of literature. Transfusion. 2015 Feb;55(2):259-64. doi: 10.1111/trf.12815. Epub 2014 Aug 25.

  PMID: 25156334 BACKGROUND

• Cao L, Koh LP, Linn YC. Successful treatment of refractory autoimmune hemolytic anemia after allogeneic hematopoietic stem cell transplantation with bortezomib. Leuk Lymphoma. 2018 Oct;59(10):2500-2502. doi: 10.1080/10428194.2017.1421759. Epub 2018 Jan 18. No abstract available.

  PMID: 29345206 BACKGROUND

MeSH Terms

Conditions

Anemia, Hemolytic, Autoimmune; Evans Syndrome; Recurrence

Interventions

Bortezomib; Rituximab; Injections

Condition Hierarchy (Ancestors)

Anemia, Hemolytic; Anemia; Hematologic Diseases; Hemic and Lymphatic Diseases; Autoimmune Diseases; Immune System Diseases; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Boronic Acids; Acids, Noncarboxylic; Acids; Inorganic Chemicals; Boron Compounds; Organic Chemicals; Pyrazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Drug Administration Routes; Drug Therapy; Therapeutics

Study Officials

• Bing Han

  Peking Union Medical College Hospital

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: associate professor

Study Record Dates

• First Submitted: August 31, 2019
• First Posted: September 10, 2019
• Study Start: August 20, 2019
• Primary Completion: March 1, 2024
• Study Completion: March 20, 2024
• Last Updated: April 26, 2024

Record last verified: 2024-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, 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.

Locations

CN (1)