AzTrials
AzTrials

Autoimmune Hemolytic AnemiaPhase 2RRAIHA01NCT04083014

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

A Phase 2 study testing combination of a single dose anti-CD20 antibody and bortezomib in people with Autoimmune Hemolytic Anemia and Autoimmune Hemolytic Anemia and Autoimmune Thrombocytopenia, run by Peking Union Medical College Hospital at 1 site in China.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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). Read more about this study

Who is it for?
Ages 18 to 80 years
What is being tested?
combination of a single dose anti-CD20 antibody and bortezomib
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
33 participants
Where
1 siteChina
Study dates
20 Aug 2019to 20 Mar 2024
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 80 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.

Who cannot join

  • 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.

Trial locations and contacts

1 site in 1 country.

China1 site

  • Peking Union Medical College Hospital

    Beijing, Beijing Municipality, 100730

Other trials in China

About this study

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

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.

Read the 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.

Being tested
combination of a single dose anti-CD20 antibody and bortezomib
Keywords
warm autoimmune hemolytic anemia, relapsed, refractory, EVANS syndrome, anti-CD20 monoclonal antibody, bortezomib
Medical subject headings
Anemia, Hemolytic, Autoimmune, Evans Syndrome, Recurrence

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • combination of a single dose anti-CD20 antibody and bortezomibDrug

    Also called Rituximab Injection, Bortezomib for Injection

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

Study groups in NCT04083014
Study groupRoleWhat they receive
study groupExperimentalThe 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.
Receives: Drug: combination of a single dose anti-CD20 antibody and bortezomib

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. response time

    days hemoglobin increasing more than 20g/L

    Measured: two years

  2. overall response

    total of complete response and partial response

    Measured: two years

  3. complete response

    rate of achieving complete response

    Measured: two years

  4. relapse rate

    relapse rate of responders

    Measured: two years

Secondary outcomes (3)

  1. relapse free survival

    time duration of responders from first treatment to recurrence of decompensated hemolysis

    Measured: two years

  2. overall survival

    time from first treatment to death of any causes

    Measured: two years

  3. side effects

    side effects due to the combination of anti-CD20 antibody and bortezomib

    Measured: two years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted10 Sep 2019
  2. Study start20 Aug 2019
  3. Primary completion1 Mar 2024
  4. Study completion20 Mar 2024

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
33 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04083014
Sponsor's protocol ID
HS-2053
Acronym
RRAIHA01
Status last verified
Apr 2024
First submitted
31 Aug 2019
Last updated
26 Apr 2024
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
Yes: Patients age,gender,diagnosis,treatment details, efficiency and survival.

Publications

  • 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.

    PubMed 20548093

  • 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.

    PubMed 28468084

  • 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.

    PubMed 30504336

  • 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.

    PubMed 18976291

  • 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.

    PubMed 8087845

  • 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.

    PubMed 18217957

  • 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.

    PubMed 12200047

  • 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.

    PubMed 29296693

  • 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.

    PubMed 31202670

  • 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.

    PubMed 25497766

  • 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.

    PubMed 21271614

  • 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.

    PubMed 25156334

  • 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.

    PubMed 29345206

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing combination of a single dose anti-CD20 antibody and bortezomib in people with Autoimmune Hemolytic Anemia and Autoimmune Hemolytic Anemia and Autoimmune Thrombocytopenia, run by Peking Union Medical College Hospital at 1 site in China.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 6 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 26 Apr 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

response time (time frame: two years). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04083014, which also lists 13 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 Apr 2024.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in