Study of Human Umbilical Cord-derived Mesenchymal Stem Cells for Treatment of Refractory Immune Thrombocytopenia

NCT04014166 | Completed DMC

• 1 other identifier: SC2019002
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 1

Brief Summary

Primary Objective: To evaluate the safety and efficacy of human umbilical cord-derived mesenchymal stem cells（hUC-MSCs） to treat refractory immune thrombocytopenia（ITP）. Secondary Objective: To observe the changes of immune function in refractory ITP patients with human umbilical cord-derived mesenchymal stem cells（hUC-MSCs） after infusion, and to explore and reveal the mechanism of hUC-MSCs in treating ITP.

Conditions

Thrombocytopenia; Mesenchymal Stem Cells

Keywords

Thrombocytopenia

Outcome Measures

Primary Outcomes (3)

• Changes of the platelet counts after hUC-MSCs infusion

  The investigator will assess the changes of the platelet counts after hUC-MSCs infusion from week 1 to week 28.

  28 weeks

• Incidence of adverse events after hUC-MSCs infusion

  The investigator will observe incidence of adverse events during and after hUC-MSCs infusion, including fever, thrombosis, diarrhea, skin rash and so on.

  4 weeks

• Changes in virus safety indicators after hUC-MSCs infusion

  The investigator will complete virus detection( including HBV, HCV, HIV, Syphilis, EB, CMV, etc) at week 4 and week 16 after hUC-MSCs infusion.

  16 weeks

Secondary Outcomes (3)

• Changes of concentration of hUC-MSCs in peripheral blood

  96 hours

• Changes of antibody production of hUC-MSCs in peripheral blood

  24 days

• Changes of immune function in refractory ITP patients after hUC-MSCs infusion

  28 weeks

Study Arms (1)

15 refractory ITP patients

EXPERIMENTAL

15 enrolled refractory ITP patients will be picked up to infuse hUC-MSCs at the indicated dose.

Other: Human umbilical cord-derived mesenchymal stem cells (hUC-MSCs)

Interventions

Human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) OTHER

This is a single-arm study to evaluate the safety and efficacy of hUC-MSCs to treat refractory immune thrombocytopenia. The dose of hUC-MSCs will be successively divided into three increasing dose(group A: hUC-MSCs 0.5×10\^6/kg, weekly for 4 weeks, 3 patients; group B: hUC-MSCs 1.0×10\^6/kg, weekly for 4 weeks, 3 patients; hUC-MSCs 2.0×10\^6/kg, weekly for 4 weeks, 3 patients) with 3 patients in each group according to the dose. The principle of increasing dose will be carried out successively from low dose to high dose group. According to the results of the safety and efficacy data from these 9 patients, the investigator will determine one of the doses and expand the sample size to 6 cases.

15 refractory ITP patients

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Aged 18 to 60 years old, male or female;
• Conform to the diagnostic criteria of immune Thrombocytopenia (ITP);
• Three months after splenectomy;
• The first-line treatment drugs such as human immunoglobulin, glucocorticoid, and the second-line treatment of thrombopoietin drugs and rituximab were invalid, or there was no response or recurrence after splenectomy;
• Diagnosis of ITP\>6 months；
• More than 3 months after rituximab treatment；
• Platelet counts \<30 ×10\^9/L, and bleeding tendency;
• People who are willing to sign the informed consent voluntarily and follow the research program.
• Subject is practicing an acceptable method of contraception. Women of childbearing potential must have a negative serum pregnancy test in the whole study;

You may not qualify if:

• ECOG score standard \>2；
• Secondary thrombocytopenic purpura;
• Patients with poor compliance;
• Positive serology for HIV, hepatitis B virus (HBV), hepatitis C virus (HCV), and/or hepatitis D virus (HDV), Syphilis; Positive for Epstein-Barr Virus DNA, Cytomegalovirus DNA;
• Pregnancy or lactation period;
• History of thrombosis;
• The serum chemistry results exceed the upper laboratory normal range by more than 20%, such as ALT, AST, TBIL, BUN, Cre etc;
• Pre-existing cardiac disease, including congestive heart failure of New York Heart Association \[NYHA\] Grade III/IV, arrhythmia requiring treatment or myocardial infarction within the last 6 months. No arrhythmia known to increase the risk of thrombotic events (e.g. atrial fibrillation), or patients with a QT \>450msec or QTc \> 480 for patients with a Bundle Branch Block;
• History of solid organ or bone marrow transplant;
• Researchers believe that patients should not participate in the test of any other condition.

Sponsors & Collaborators

• Institute of Hematology & Blood Diseases Hospital, China: lead

Study Sites (1)

Yunfei Chen

Tianjin, Tianjin Municipality, 300020, China

Location

Related Publications (9)

• Wang X, Yin X, Sun W, Bai J, Shen Y, Ao Q, Gu Y, Liu Y. Intravenous infusion umbilical cord-derived mesenchymal stem cell in primary immune thrombocytopenia: A two-year follow-up. Exp Ther Med. 2017 May;13(5):2255-2258. doi: 10.3892/etm.2017.4229. Epub 2017 Mar 14.

  PMID: 28565834 BACKGROUND

• Wang Y, Han ZB, Ma J, Zuo C, Geng J, Gong W, Sun Y, Li H, Wang B, Zhang L, He Y, Han ZC. A toxicity study of multiple-administration human umbilical cord mesenchymal stem cells in cynomolgus monkeys. Stem Cells Dev. 2012 Jun 10;21(9):1401-8. doi: 10.1089/scd.2011.0441. Epub 2011 Nov 22.

  PMID: 21958114 BACKGROUND

• Wang Y, Zhang Z, Chi Y, Zhang Q, Xu F, Yang Z, Meng L, Yang S, Yan S, Mao A, Zhang J, Yang Y, Wang S, Cui J, Liang L, Ji Y, Han ZB, Fang X, Han ZC. Long-term cultured mesenchymal stem cells frequently develop genomic mutations but do not undergo malignant transformation. Cell Death Dis. 2013 Dec 5;4(12):e950. doi: 10.1038/cddis.2013.480.

  PMID: 24309937 BACKGROUND

• Gong W, Han Z, Zhao H, Wang Y, Wang J, Zhong J, Wang B, Wang S, Wang Y, Sun L, Han Z. Banking human umbilical cord-derived mesenchymal stromal cells for clinical use. Cell Transplant. 2012;21(1):207-16. doi: 10.3727/096368911X586756. Epub 2011 Sep 16.

  PMID: 21929848 BACKGROUND

• Wu Y, Wang Z, Cao Y, Xu L, Li X, Liu P, Yan P, Liu Z, Zhao D, Wang J, Wu X, Gao C, Da W, Han Z. Cotransplantation of haploidentical hematopoietic and umbilical cord mesenchymal stem cells with a myeloablative regimen for refractory/relapsed hematologic malignancy. Ann Hematol. 2013 Dec;92(12):1675-84. doi: 10.1007/s00277-013-1831-0. Epub 2013 Jul 11.

  PMID: 23842707 BACKGROUND

• Liang J, Zhang H, Hua B, Wang H, Wang J, Han Z, Sun L. Allogeneic mesenchymal stem cells transplantation in treatment of multiple sclerosis. Mult Scler. 2009 May;15(5):644-6. doi: 10.1177/1352458509104590.

  PMID: 19389752 BACKGROUND

• Wu Y, Cao Y, Li X, Xu L, Wang Z, Liu P, Yan P, Liu Z, Wang J, Jiang S, Wu X, Gao C, Da W, Han Z. Cotransplantation of haploidentical hematopoietic and umbilical cord mesenchymal stem cells for severe aplastic anemia: successful engraftment and mild GVHD. Stem Cell Res. 2014 Jan;12(1):132-8. doi: 10.1016/j.scr.2013.10.001. Epub 2013 Oct 10.

  PMID: 24185180 BACKGROUND

• Ma L, Zhou Z, Zhang D, Yang S, Wang J, Xue F, Yang Y, Yang R. Immunosuppressive function of mesenchymal stem cells from human umbilical cord matrix in immune thrombocytopenia patients. Thromb Haemost. 2012 May;107(5):937-50. doi: 10.1160/TH11-08-0596. Epub 2012 Mar 8.

  PMID: 22398715 RESULT

• Chen Y, Xu Y, Chi Y, Sun T, Gao Y, Dou X, Han Z, Xue F, Li H, Liu W, Liu X, Dong H, Fu R, Ju M, Dai X, Wang W, Ma Y, Song Z, Gu J, Gong W, Yang R, Zhang L. Efficacy and safety of human umbilical cord-derived mesenchymal stem cells in the treatment of refractory immune thrombocytopenia: a prospective, single arm, phase I trial. Signal Transduct Target Ther. 2024 Apr 23;9(1):102. doi: 10.1038/s41392-024-01793-5.

  PMID: 38653983 DERIVED

MeSH Terms

Conditions

Thrombocytopenia

Condition Hierarchy (Ancestors)

Blood Platelet Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Cytopenia

Study Officials

• Lei Zhang, MD

  Chinese Academy of Medical Science and Blood Disease Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 7, 2019
• First Posted: July 10, 2019
• Study Start: November 21, 2019
• Primary Completion: February 28, 2023
• Study Completion: June 30, 2023
• Last Updated: February 21, 2025

Record last verified: 2023-06

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: From 12 months 36 months after study completion.
• Access Criteria: Upon request to PI.

Locations

CN (1)