The Effect of Sirolimus on Immunizations During the Treatment of Kaposiform Hemangioendothelioma

The Effect of Sirolimus on Time-sequentially Scheduled Immunizations During the Treatment of Kaposiform Hemangioendothelioma: a Case-control Study

To research and explore the antibody protection and immune memory after vaccination in children with KHE during sirolimus administration. To explore the feasibility (safety and efficacy) of vaccination in a timely manner during the administration of sirolimus in children with KHE. To search for back-up plans for vaccination regimens for KHE patients taking sirolimus in children who do not respond to primary vaccination.

Study Overview

• Status: Recruiting
• Conditions: Kaposiform Hemangioendothelioma
• Intervention / Treatment: Other

Detailed Description

Children with KHE have an early onset. KHE usually occurs in infants and young children less than 1 year old, of which neonates account for about 38.5%-60% of all cases. Due to the immunosuppressive effect of sirolimus, the vaccination was usually suspended after taking it, and children would be in a state of no immune protection. These children are at greatly increased risk of exposure to microorganisms and consequent infection. Therefore, it is necessary to vaccinate them against infectious diseases. However, vaccination with live vaccines has the potential to cause severe infections through reversion of the vaccine strain to a pathogenic form. Moreover, studies have also shown that protective antibodies are severely affected in transplant patients taking immunosuppressive drugs and in patients with solid tumors after chemotherapy. Loss of immune memory is very common, and marked deficits in B cell function and humoral immunity can persist even for years.

• Study Type: Observational
• Enrollment (Estimated): 174

Contacts and Locations

• Study Contact: Name: Kai Li, PhD; Phone Number: 02164931114; Email: likai2727@163.com

Study Locations

• China
  • Shanghai
    • Shanghai, Shanghai, China, 201102
      • Recruiting
      • Children's Hospital of Fudan University
      • Contact: Kai Li, Doctor

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 12 years (Child)
• Accepts Healthy Volunteers: Yes

• Sampling Method: Probability Sample

Study Population

The calculation of the sample size came from the previous pre-experiment. Investigator take HBsAb protection rate as the main outcome indicator. The sample size of this study, calculated using a non-inferiority test, was 156 (78 per group). In addition, 10% was required to make up for loss to follow-up, withdrawal, etc. So a total of 174 subjects (87 per group) are anticipated.

Description

Inclusion Criteria:

• Case groups:
• KHE patients treated with sirolimus.
• After immunoglobulin and flow cytometry assays, as well as outpatient evaluation and assessment, those participants will be vaccinated with live attenuated vaccines or inactivated vaccines in a timely order according to the advice.
• Control groups:
• Healthy children with no immune deficiencies.
• Participants are vaccinated according to the National Immunization Program in a timely manner.
• Participants are matched to the case group according to age.

Exclusion Criteria:

• HBsAg, HBeAg positive, or other active infectious diseases;
• History of immunodeficiency or low immunoglobulin levels;
• Autoimmune disease or fever during blood collection;
• Use of other medication or surgery;
• Suffering from other bleeding disorders;
• Suffering from other solid tumors or hematological tumors, etc.;
• Withdraw informed consent.

Study Plan

How is the study designed?

Design Details

• Observational Models: Case-Control
• Time Perspectives: Prospective

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort
Cases; Individuals diagnosed with KHE and treated with sirolimus. After immunoglobulin and flow cytometry assays, as well as outpatient evaluation and assessment, those participants will be vaccinated with live attenuated vaccines or inactivated vaccines in a timely order according to the advice. （Sirolimus Rapamycin 0.8mg/m2 bid po）
Controls; Healthy children with no immunodeficiency disease, vaccinated according to the National Immunization Program. Particpants should be age-matched with the case group.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Titers of Hepatitis B virus surface antibody	Titers of Hepatitis B virus surface antibody，indicating whether there is persistent protective antibodies after vaccination.	Admission within 1 day
Titers of Hepatitis B virus surface antibody	Titers of Hepatitis B virus surface antibody，indicating whether there is persistent	The 7th month after admission
Titers of Hepatitis B virus surface antibody	Titers of Hepatitis B virus surface antibody，indicating whether there is persistent	The 12th month after admission
Titers of Hepatitis B virus surface antibody	Titers of Hepatitis B virus surface antibody，indicating whether there is persistent	The 18th month after admission

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Levels of measles antibodies.	This outcome indicates whether there is persistent protective antibodies after vaccination.	Admission within 1 day
Levels of mumps antibodies	This outcome indicates whether there is persistent protective antibodies after vaccination.	Admission within 1 day
Levels of rubella antibodies.	This outcome indicates whether there is persistent protective antibodies after vaccination.	Admission within 1 day
Levels of measles antibodies.	This outcome indicates whether there is persistent protective antibodies after vaccination.	The 7th month after admission
Levels of mumps antibodies.	This outcome indicates whether there is persistent protective antibodies after vaccination.	The 7th month after admission
Levels of rubella antibodies.	This outcome indicates whether there is persistent protective antibodies after vaccination.	The 7th month after admission
Levels of measles antibodies.	This outcome indicates whether there is persistent protective antibodies after vaccination.	The 12th month after admission
Levels of mumps antibodies.	This outcome indicates whether there is persistent protective antibodies after vaccination.	The 12th month after admission
Levels of rubella antibodies.	This outcome indicates whether there is persistent protective antibodies after vaccination.	The 12th month after admission
Levels of measles antibodies.	This outcome indicates whether there is persistent protective antibodies after vaccination.	The 18th month after admission
Levels of mumps antibodies.	This outcome indicates whether there is persistent protective antibodies after vaccination.	The 18th month after admission
Levels of rubella antibodies.	This outcome indicates whether there is persistent protective antibodies after vaccination.	The 18th month after admission
Level of Japanese encephalitis antibody.	This outcome indicates whether there is persistent protective antibodies after vaccination.	Admission within 1 day
Level of Japanese encephalitis antibody.	This outcome indicates whether there is persistent protective antibodies after vaccination.	The 7th month after admission
Level of Japanese encephalitis antibody.	This outcome indicates whether there is persistent protective antibodies after vaccination.	The 12th month after admission
Level of Japanese encephalitis antibody.	This outcome indicates whether there is persistent protective antibodies after vaccination.	The 18th month after admission
Level of varicella antibody	This outcome indicates whether there is persistent protective antibodies after vaccination.	Admission within 1 day
Level of varicella antibody.	This outcome indicates whether there is persistent protective antibodies after vaccination.	The 7th month after admission
Level of varicella antibody.	This outcome indicates whether there is persistent protective antibodies after vaccination.	The 12th month after admission
Level of varicella antibody.	This outcome indicates whether there is persistent protective antibodies after vaccination.	The 18th month after admission
Level of COVID-19 antibody.	This outcome indicates whether there is persistent protective antibodies after vaccination.	Admission within 1 day
Level of COVID-19 antibody.	This outcome indicates whether there is persistent protective antibodies after vaccination.	The 7th month after admission
Level of COVID-19 antibody.	This outcome indicates whether there is persistent protective antibodies after vaccination.	The 12th month after admission
Level of COVID-19 antibody.	This outcome indicates whether there is persistent protective antibodies after vaccination.	The 18th month after admission

Collaborators and Investigators

• Sponsor: Children's Hospital of Fudan University
• Investigators: Principal Investigator: Kai Li, PhD, Children's Hospital of Fudan University

Publications and helpful links

General Publications

• Zignol M, Peracchi M, Tridello G, Pillon M, Fregonese F, D'Elia R, Zanesco L, Cesaro S. Assessment of humoral immunity to poliomyelitis, tetanus, hepatitis B, measles, rubella, and mumps in children after chemotherapy. Cancer. 2004 Aug 1;101(3):635-41. doi: 10.1002/cncr.20384.
• Kwon HJ, Lee JW, Chung NG, Cho B, Kim HK, Kang JH. Assessment of serologic immunity to diphtheria-tetanus-pertussis after treatment of Korean pediatric hematology and oncology patients. J Korean Med Sci. 2012 Jan;27(1):78-83. doi: 10.3346/jkms.2012.27.1.78. Epub 2011 Dec 19.
• Zhang J, Xie F, Delzell E, Chen L, Winthrop KL, Lewis JD, Saag KG, Baddley JW, Curtis JR. Association between vaccination for herpes zoster and risk of herpes zoster infection among older patients with selected immune-mediated diseases. JAMA. 2012 Jul 4;308(1):43-9. doi: 10.1001/jama.2012.7304.
• Kawano Y, Suzuki M, Kawada J, Kimura H, Kamei H, Ohnishi Y, Ono Y, Uchida H, Ogura Y, Ito Y. Effectiveness and safety of immunization with live-attenuated and inactivated vaccines for pediatric liver transplantation recipients. Vaccine. 2015 Mar 17;33(12):1440-5. doi: 10.1016/j.vaccine.2015.01.075. Epub 2015 Feb 7.
• Inoue T, Moran I, Shinnakasu R, Phan TG, Kurosaki T. Generation of memory B cells and their reactivation. Immunol Rev. 2018 May;283(1):138-149. doi: 10.1111/imr.12640.
• Vink P, Ramon Torrell JM, Sanchez Fructuoso A, Kim SJ, Kim SI, Zaltzman J, Ortiz F, Campistol Plana JM, Fernandez Rodriguez AM, Rebollo Rodrigo H, Campins Marti M, Perez R, Gonzalez Roncero FM, Kumar D, Chiang YJ, Doucette K, Pipeleers L, Aguera Morales ML, Rodriguez-Ferrero ML, Secchi A, McNeil SA, Campora L, Di Paolo E, El Idrissi M, Lopez-Fauqued M, Salaun B, Heineman TC, Oostvogels L; Z-041 Study Group. Immunogenicity and Safety of the Adjuvanted Recombinant Zoster Vaccine in Chronically Immunosuppressed Adults Following Renal Transplant: A Phase 3, Randomized Clinical Trial. Clin Infect Dis. 2020 Jan 2;70(2):181-190. doi: 10.1093/cid/ciz177.
• Saghafian-Hedengren S, Soderstrom I, Sverremark-Ekstrom E, Nilsson A. Insights into defective serological memory after acute lymphoblastic leukaemia treatment: The role of the plasma cell survival niche, memory B-cells and gut microbiota in vaccine responses. Blood Rev. 2018 Jan;32(1):71-80. doi: 10.1016/j.blre.2017.08.009. Epub 2017 Aug 26.
• Horns F, Dekker CL, Quake SR. Memory B Cell Activation, Broad Anti-influenza Antibodies, and Bystander Activation Revealed by Single-Cell Transcriptomics. Cell Rep. 2020 Jan 21;30(3):905-913.e6. doi: 10.1016/j.celrep.2019.12.063.
• Dini G, Toletone A, Barberis I, Debarbieri N, Massa E, Paganino C, Bersi F, Montecucco A, Alicino C, Durando P. Persistence of protective anti-HBs antibody levels and anamnestic response to HBV booster vaccination: A cross-sectional study among healthcare students 20 years following the universal immunization campaign in Italy. Hum Vaccin Immunother. 2017 Feb;13(2):440-444. doi: 10.1080/21645515.2017.1264788.
• Zhang L, Thornton CP, Ruble K, Cooper SL. Post-Chemotherapy Titer Status and Need for Revaccination After Treatment for Childhood Cancer. Clin Pediatr (Phila). 2020 Jun;59(6):606-613. doi: 10.1177/0009922820915884.

Study record dates

Study Major Dates

• Study Start (Actual): March 1, 2021
• Primary Completion (Estimated): March 1, 2026
• Study Completion (Estimated): March 1, 2028

Study Registration Dates

• First Submitted: March 30, 2022
• First Submitted That Met QC Criteria: April 22, 2022
• First Posted (Actual): April 28, 2022

Study Record Updates

• Last Update Posted (Actual): June 27, 2025
• Last Update Submitted That Met QC Criteria: June 24, 2025
• Last Verified: June 1, 2025

More Information

Terms related to this study

• Keywords: Sirolimus; Following National Vaccination Program
• Additional Relevant MeSH Terms: Cytopenia; Neoplasms; Infections; Virus Diseases; Neoplasms by Histologic Type; Hematologic Diseases; DNA Virus Infections; Sarcoma; Neoplasms, Connective and Soft Tissue; Herpesviridae Infections; Blood Platelet Disorders; Neoplasms, Vascular Tissue; Thrombocytopenia; Hemangioma; Sarcoma, Kaposi; Hemangioendothelioma; Kasabach-Merritt Syndrome
• Other Study ID Numbers: LK220323

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No