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Sirolimus in the Treatment of Refractory/Relapsed wAIHA

Primary Purpose

Warm Autoimmune Hemolytic Anemia

Status
Recruiting
Phase
Phase 2
Locations
China
Study Type
Interventional
Intervention
Sirolimus
Sponsored by
Peking Union Medical College Hospital
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Warm Autoimmune Hemolytic Anemia focused on measuring warm autoimmune hemolytic anemia, Evans syndrome, refractory/relapsed, sirolimus, efficacy

Eligibility Criteria

18 Years - 90 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: Age ≥18 years old. Diagnosed as primary warm autoimmune hemolytic anemia or Evans syndrome (primary or secondary). There is no treatment indication of other systemic involvement in the original disease if secondary. No response to glucocorticoid therapy or recurrence. Baseline liver (ALT, AST) was less than 2 times the normal value. No active infection; Not pregnant or breastfeeding. Agree to sign the consent form. Exclusion Criteria: Patients with connective tissue disease or other organs involvement Infection or bleeding that cannot be controlled by standard treatment. Active HIV, HCV or HBV infection or cirrhosis or portal hypertension. Progressed uncontrolled malignant tumors and lymphoma Cirrhosis or portal hypertension. Pregnant or breastfeeding.

Sites / Locations

  • Peking Union Medical College HospitalRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Sirolimus on refractory/relapsed wAIHA

Arm Description

A prospective research of the sirolimus efficiency on refractory/relapsed primary wAIHA patients. Sirolimus dosage: 1-3 mg/d with plasma concentration 4-15ng/mL. Medication time should last at least 6 months. After reaching the optimal response, responders continue to use sirolimus for 1 year, and then gradually reduce the dosage.

Outcomes

Primary Outcome Measures

Overall response rate (ORR)
ORR defined as the proportion of patients who met the criteria of either complete response (CR) or partial response (PR).

Secondary Outcome Measures

Complete response rate (CRR
CRR defined as the proportion of patients who met the criteria of complete response.
Adverse events
Safety analyses include assessments of the incidence and severity of adverse events; all adverse events that occurred or worsened during the treatment period will be reported, as well as adverse events that occurred later but are considered by the investigator to be related to the trial drug.
Relapse rate
Relapse rate defined as the proportion of patients whose response shift from PR or CR to no response (NR).

Full Information

First Posted
June 21, 2023
Last Updated
August 16, 2023
Sponsor
Peking Union Medical College Hospital
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1. Study Identification

Unique Protocol Identification Number
NCT05925023
Brief Title
Sirolimus in the Treatment of Refractory/Relapsed wAIHA
Official Title
Sirolimus in the Treatment of Refractory/Relapsed Warm Autoimmune Hemolytic Anemia (AIHA): a Phase 2 Prospective Trial
Study Type
Interventional

2. Study Status

Record Verification Date
August 2023
Overall Recruitment Status
Recruiting
Study Start Date
June 24, 2023 (Actual)
Primary Completion Date
December 2024 (Anticipated)
Study Completion Date
December 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Peking Union Medical College Hospital

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
Autoimmune hemolytic anemia (AIHA) is a rare and heterogeneous disorder characterized by the destruction of red blood cells through warm or cold antibodies. Glucocorticoid (combined with rituximab) is the first-line treatment. However, the recurrence rate is very high and some patients may not respond to steroids. Second-line therapies include cyclosporine A (CsA), cyclophosphamide, rituximab, azathioprine, and even splenectomy. Our previous study of sirolimus in refractory/relapsed AIHA and ES found an effective rate of 80%. Therefore, the investigators plan to explore the efficacy and safety of sirolimus in the treatment of refractory/relapsed wAIHA.
Detailed Description
Based on the optimal autoantibody-RBC reactivity temperatures, AIHA is classified into warm type, cold type, and mixed type. AIHA can be further classified into primary or secondary in nature. Glucocorticoid (combined with rituximab) is the first-line treatment. However, the recurrence rate is very high and some patients may not respond to steroids. Second-line therapies include cyclosporine A (CsA), cyclophosphamide, rituximab, azathioprine, and even splenectomy. The refractory/relapsed wAIHA patients have increased cardiovascular events, increased opportunities for infections, decreased quality of life, and even death. A prospective multi-institutional trial in autoimmune cytopenia found that 8 of 10 patients with AIHA and Evans syndrome respond to sirolimus. Our previous study of sirolimus in refractory/relapsed AIHA and ES also found an effective rate of approximately 80%. Since sirolimus is cheap and accessible, our findings may reduce the economic burden of patients and be a guide on the selection of second-line treatment drugs in refractory/relapsed wAIHA and Evans syndrome.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Warm Autoimmune Hemolytic Anemia
Keywords
warm autoimmune hemolytic anemia, Evans syndrome, refractory/relapsed, sirolimus, efficacy

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
22 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Sirolimus on refractory/relapsed wAIHA
Arm Type
Experimental
Arm Description
A prospective research of the sirolimus efficiency on refractory/relapsed primary wAIHA patients. Sirolimus dosage: 1-3 mg/d with plasma concentration 4-15ng/mL. Medication time should last at least 6 months. After reaching the optimal response, responders continue to use sirolimus for 1 year, and then gradually reduce the dosage.
Intervention Type
Drug
Intervention Name(s)
Sirolimus
Intervention Description
Oral administration, 1-3 mg/d, sirolimus plasma concentration: 4-15 ng/mL
Primary Outcome Measure Information:
Title
Overall response rate (ORR)
Description
ORR defined as the proportion of patients who met the criteria of either complete response (CR) or partial response (PR).
Time Frame
12 months
Secondary Outcome Measure Information:
Title
Complete response rate (CRR
Description
CRR defined as the proportion of patients who met the criteria of complete response.
Time Frame
12 months
Title
Adverse events
Description
Safety analyses include assessments of the incidence and severity of adverse events; all adverse events that occurred or worsened during the treatment period will be reported, as well as adverse events that occurred later but are considered by the investigator to be related to the trial drug.
Time Frame
12 months
Title
Relapse rate
Description
Relapse rate defined as the proportion of patients whose response shift from PR or CR to no response (NR).
Time Frame
12 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
90 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Age ≥18 years old. Diagnosed as primary warm autoimmune hemolytic anemia or Evans syndrome (primary or secondary). There is no treatment indication of other systemic involvement in the original disease if secondary. No response to glucocorticoid therapy or recurrence. Baseline liver (ALT, AST) was less than 2 times the normal value. No active infection; Not pregnant or breastfeeding. Agree to sign the consent form. Exclusion Criteria: Patients with connective tissue disease or other organs involvement Infection or bleeding that cannot be controlled by standard treatment. Active HIV, HCV or HBV infection or cirrhosis or portal hypertension. Progressed uncontrolled malignant tumors and lymphoma Cirrhosis or portal hypertension. Pregnant or breastfeeding.
Facility Information:
Facility Name
Peking Union Medical College Hospital
City
Beijing
State/Province
Beijing
ZIP/Postal Code
100730
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Miao Chen
Phone
+86 13520112578
Email
chenm@pumch.cn
First Name & Middle Initial & Last Name & Degree
Bing Han
Phone
+86 69155028
Email
hanbingpumch@163.com

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
31839434
Citation
Jager U, Barcellini W, Broome CM, Gertz MA, Hill A, Hill QA, Jilma B, Kuter DJ, Michel M, Montillo M, Roth A, Zeerleder SS, Berentsen S. Diagnosis and treatment of autoimmune hemolytic anemia in adults: Recommendations from the First International Consensus Meeting. Blood Rev. 2020 May;41:100648. doi: 10.1016/j.blre.2019.100648. Epub 2019 Dec 5.
Results Reference
background
PubMed Identifier
24418298
Citation
Bass GF, Tuscano ET, Tuscano JM. Diagnosis and classification of autoimmune hemolytic anemia. Autoimmun Rev. 2014 Apr-May;13(4-5):560-4. doi: 10.1016/j.autrev.2013.11.010. Epub 2014 Jan 11.
Results Reference
background
PubMed Identifier
28005293
Citation
Hill QA, Stamps R, Massey E, Grainger JD, Provan D, Hill A; British Society for Haematology. The diagnosis and management of primary autoimmune haemolytic anaemia. Br J Haematol. 2017 Feb;176(3):395-411. doi: 10.1111/bjh.14478. Epub 2016 Dec 22. No abstract available.
Results Reference
background
PubMed Identifier
33512406
Citation
Barcellini W, Fattizzo B. How I treat warm autoimmune hemolytic anemia. Blood. 2021 Mar 11;137(10):1283-1294. doi: 10.1182/blood.2019003808. Erratum In: Blood. 2023 Jan 26;141(4):438-439.
Results Reference
background
PubMed Identifier
23981017
Citation
Birgens H, Frederiksen H, Hasselbalch HC, Rasmussen IH, Nielsen OJ, Kjeldsen L, Larsen H, Mourits-Andersen T, Plesner T, Ronnov-Jessen D, Vestergaard H, Klausen TW, Schollkopf C. A phase III randomized trial comparing glucocorticoid monotherapy versus glucocorticoid and rituximab in patients with autoimmune haemolytic anaemia. Br J Haematol. 2013 Nov;163(3):393-9. doi: 10.1111/bjh.12541. Epub 2013 Aug 24.
Results Reference
background
PubMed Identifier
25232059
Citation
Barcellini W, Fattizzo B, Zaninoni A, Radice T, Nichele I, Di Bona E, Lunghi M, Tassinari C, Alfinito F, Ferrari A, Leporace AP, Niscola P, Carpenedo M, Boschetti C, Revelli N, Villa MA, Consonni D, Scaramucci L, De Fabritiis P, Tagariello G, Gaidano G, Rodeghiero F, Cortelezzi A, Zanella A. Clinical heterogeneity and predictors of outcome in primary autoimmune hemolytic anemia: a GIMEMA study of 308 patients. Blood. 2014 Nov 6;124(19):2930-6. doi: 10.1182/blood-2014-06-583021. Epub 2014 Sep 16.
Results Reference
background
PubMed Identifier
26504182
Citation
Bride KL, Vincent T, Smith-Whitley K, Lambert MP, Bleesing JJ, Seif AE, Manno CS, Casper J, Grupp SA, Teachey DT. Sirolimus is effective in relapsed/refractory autoimmune cytopenias: results of a prospective multi-institutional trial. Blood. 2016 Jan 7;127(1):17-28. doi: 10.1182/blood-2015-07-657981. Epub 2015 Oct 26.
Results Reference
background
PubMed Identifier
32771553
Citation
Li H, Ji J, Du Y, Huang Y, Gu H, Chen M, Wu R, Han B. Sirolimus is effective for primary relapsed/refractory autoimmune cytopenia: a multicenter study. Exp Hematol. 2020 Sep;89:87-95. doi: 10.1016/j.exphem.2020.08.001. Epub 2020 Aug 6.
Results Reference
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Sirolimus in the Treatment of Refractory/Relapsed wAIHA

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