Efficacy and Safety of UCBT With TMI -Based Conditioning Regimen for Adults With Refractory/Relapsed Aplastic Anemia

NCT07078721 | Not Yet Recruiting Phase 2 DMC

• 1 other identifier: IIT2025071
• Study Type: interventional
• Target: 11
• Locations: 1 country
• Sites: 1

Brief Summary

Refractory/relapsed aplastic anemia (AA) in adults remains a clinical challenge that is frequently encountered and urgently needs to be resolved. Salvage treatment should prioritize hematopoietic stem cell transplantation (HSCT). Unrelated cord blood is an ideal source of hematopoietic stem cells due to its easy availability, low immunogenicity, and low incidence of chronic graft-versus-host disease (cGVHD) after transplantation.The optimization of the conditioning regimen for UCBT is a crucial factor in determining patient outcomes. This is a Phase II clinical study. A total of 11 adult patients with refractory/relapsed AA will be treated with a UCBT regimen based on a TMI-based conditioning regimen. Patients who meet the inclusion/exclusion criteria will sign an informed consent form before undergoing cord blood transplantation. The efficacy (12-month EFS) and safety of the regimen will be assessed 12 months after transplantation.

Conditions

Aplastic Anemia Idiopathic

Keywords

aplastic anemia; refractory/relapsed; Total Marrow Irradiation; Umbilical Cord Blood Transplantation

Outcome Measures

Primary Outcomes (1)

• Event-free survival (EFS) at 12 months post-transplant.

  Event-free survival (EFS): Defined as the time from the start of UCBT to the occurrence of an event, including death, graft failure, lack of response, relapse, and clonal progression.

  ---Enrollment Period (2 weeks)---Treatment Period (7 days)---Follow-Up Period (12 months)

Study Arms (1)

TMI in AA

EXPERIMENTAL

Efficacy and Safety Study of Umbilical Cord Blood Transplantation (UCBT) with Total Marrow Irradiation (TMI)-Based Conditioning Regimen for Adults with Refractory/Relapsed Aplastic Anemia (AA)

Radiation: Total Marrow Irradiation; Drug: Fludarabine (FLU); Drug: Melphalan (Mel)

Interventions

Total Marrow Irradiation RADIATION

\- TMI 4 Gy qd on Day -2;

Also known as: Marrow-Targeted Radiotherapy, Organ-Sparing Marrow-Targeted Irradiation (OSMI)

TMI in AA

Fludarabine (FLU) DRUG

Flu 30 mg/m² × 5 days on Days -6, -5, -4, -3, -2;

Also known as: FaraA

TMI in AA

Melphalan (Mel) DRUG

Mel 100 mg/m² qd on Day -1.

Also known as: L-PAM

TMI in AA

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Subjects suitable for enrollment in this study must meet all of the following criteria:
• Age ≥18 years and \<50 years, regardless of gender.
• Diagnosis of AA according to the guidelines of the British Society for Haematology. The bone marrow shows hypocellularity, without infiltration of abnormal cells or marrow fibrosis. The peripheral blood must meet at least two of the following three criteria: absolute neutrophil count (ANC) \<1.5×10⁹/L; platelet count \<50×10⁹/L; hemoglobin \<100 g/L. Based on the severity of the disease, AA is classified into severe aplastic anemia (SAA) and non-severe aplastic anemia (NSAA).
• The diagnostic criteria for severe aplastic anemia (SAA) are as follows:
• Peripheral blood criteria
• At least two of the following three criteria must be met:
• Absolute neutrophil count (ANC) \<0.5×10⁹/L; Reticulocyte count \<20×10⁹/L; Platelet count \<20×10⁹/L; Bone marrow criteria The degree of bone marrow cellularity is \<25% of normal; if ≥25% but \<50% of normal, then the proportion of residual hematopoietic cells should be \<30%.
• Bone marrow aspiration results show hypocellular or severely hypocellular marrow, with a marked decrease in hematopoietic cells and an increase in non-hematopoietic cells such as lymphocytes and reticular cells.
• Other：Other diseases causing pancytopenia, such as myelodysplastic syndrome (MDS), paroxysmal nocturnal hemoglobinuria (PNH), and congenital marrow failure syndromes, should be excluded.
• If ANC \<0.2×10⁹/L, the diagnosis is very severe aplastic anemia (VSAA); Those who do not meet the criteria for SAA are classified as non-severe aplastic anemia (NSAA);
• Meet the criteria for refractory AA: ①SAA: no response to first-line ATG + CSA treatment for more than 6 months; ②NSAA: ①persistent transfusion dependence of two or more blood cell lines, ②meet any of the following criteria: no response to immunosuppressive therapy with cyclosporine for more than 12 months, or no response to androgen and/or TPO receptor agonist therapy for more than 6 months, ④or progression to SAA; Meet the criteria for relapsed AA: initially effective to first-line immunosuppressive therapy, but pancytopenia recurs after reduction or discontinuation of immunosuppressive therapy, meeting the criteria for SAA.
• Karnofsky score ≥60, ECOG score ≤2, HCT-CI index ≤2.
• No HLA-identical sibling donor or no HLA-identical unrelated donor available.
• Understanding of the study procedures and voluntary written informed consent.

You may not qualify if:

• Subjects with any of the following conditions are not eligible for enrollment in this study:
• Pancytopenia and hypoplastic marrow diseases caused by other reasons (including PNH, etc.).
• Use of intermediate or high doses of cyclophosphamide (≥20mg/kg/d) for immunosuppressive therapy within 3 months before enrollment.
• History of hematopoietic stem cell transplantation.
• Known or suspected contraindications or allergies to fludarabine, melphalan, or other drugs.
• Patients with uncontrolled bleeding and/or infection after standard treatment before screening.
• Active viral hepatitis (hepatitis B, hepatitis C, etc.), HIV infection, or syphilis at baseline or screening.
• Creatinine clearance rate \<60 ml/min before treatment, or serum creatinine \>140 μmol/L.
• Pregnant or breastfeeding women.
• Participation in another clinical trial within 3 months before enrollment.
• Any other condition that the investigator deems may prevent the subject from completing the study or pose significant risks to the subject.

Sponsors & Collaborators

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

Study Sites (1)

Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College

Tianjin, City, 300020, China

Location

Related Publications (10)

• Olnes MJ, Scheinberg P, Calvo KR, Desmond R, Tang Y, Dumitriu B, Parikh AR, Soto S, Biancotto A, Feng X, Lozier J, Wu CO, Young NS, Dunbar CE. Eltrombopag and improved hematopoiesis in refractory aplastic anemia. N Engl J Med. 2012 Jul 5;367(1):11-9. doi: 10.1056/NEJMoa1200931.

  PMID: 22762314 BACKGROUND

• Jagasia MH, Greinix HT, Arora M, Williams KM, Wolff D, Cowen EW, Palmer J, Weisdorf D, Treister NS, Cheng GS, Kerr H, Stratton P, Duarte RF, McDonald GB, Inamoto Y, Vigorito A, Arai S, Datiles MB, Jacobsohn D, Heller T, Kitko CL, Mitchell SA, Martin PJ, Shulman H, Wu RS, Cutler CS, Vogelsang GB, Lee SJ, Pavletic SZ, Flowers ME. National Institutes of Health Consensus Development Project on Criteria for Clinical Trials in Chronic Graft-versus-Host Disease: I. The 2014 Diagnosis and Staging Working Group report. Biol Blood Marrow Transplant. 2015 Mar;21(3):389-401.e1. doi: 10.1016/j.bbmt.2014.12.001. Epub 2014 Dec 18.

  PMID: 25529383 BACKGROUND

• Harris AC, Young R, Devine S, Hogan WJ, Ayuk F, Bunworasate U, Chanswangphuwana C, Efebera YA, Holler E, Litzow M, Ordemann R, Qayed M, Renteria AS, Reshef R, Wolfl M, Chen YB, Goldstein S, Jagasia M, Locatelli F, Mielke S, Porter D, Schechter T, Shekhovtsova Z, Ferrara JL, Levine JE. International, Multicenter Standardization of Acute Graft-versus-Host Disease Clinical Data Collection: A Report from the Mount Sinai Acute GVHD International Consortium. Biol Blood Marrow Transplant. 2016 Jan;22(1):4-10. doi: 10.1016/j.bbmt.2015.09.001. Epub 2015 Sep 16.

  PMID: 26386318 BACKGROUND

• Kurtzberg J, Troy JD, Page KM, El Ayoubi HR, Volt F, Maria Scigliuolo G, Cappelli B, Rocha V, Ruggeri A, Gluckman E. Unrelated Donor Cord Blood Transplantation in Children: Lessons Learned Over 3 Decades. Stem Cells Transl Med. 2023 Jan 30;12(1):26-38. doi: 10.1093/stcltm/szac079.

  PMID: 36718114 BACKGROUND

• Hiramoto N, Yamazaki H, Nakamura Y, Uchida N, Murata M, Kondo T, Yoshioka S, Eto T, Nishikawa A, Kimura T, Ichinohe T, Atsuta Y, Onishi Y, Suzuki R, Mori T; Adult Aplastic Anemia Working Group of the Japanese Society for Hematopoietic Cell Transplantation. Total body irradiation-containing conditioning regimens without antithymocyte globulin in adults with aplastic anemia undergoing umbilical cord blood transplantation. Ann Hematol. 2022 Jan;101(1):165-175. doi: 10.1007/s00277-021-04664-z. Epub 2021 Sep 21.

  PMID: 34546409 BACKGROUND

• Peffault de Latour R, Purtill D, Ruggeri A, Sanz G, Michel G, Gandemer V, Maury S, Kurtzberg J, Bonfim C, Aljurf M, Gluckman E, Socie G, Passweg J, Rocha V. Influence of nucleated cell dose on overall survival of unrelated cord blood transplantation for patients with severe acquired aplastic anemia: a study by eurocord and the aplastic anemia working party of the European group for blood and marrow transplantation. Biol Blood Marrow Transplant. 2011 Jan;17(1):78-85. doi: 10.1016/j.bbmt.2010.06.011. Epub 2010 Jun 16.

  PMID: 20561593 BACKGROUND

• Red Blood Cell Disease (Anemia) Group, Chinese Society of Hematology, Chinese Medical Association. [Guidelines for the diagnosis and management of aplastic anemia in China (2022)]. Zhonghua Xue Ye Xue Za Zhi. 2022 Nov 14;43(11):881-888. doi: 10.3760/cma.j.issn.0253-2727.2022.11.001. No abstract available. Chinese.

  PMID: 36709177 BACKGROUND

• Valdez JM, Scheinberg P, Nunez O, Wu CO, Young NS, Walsh TJ. Decreased infection-related mortality and improved survival in severe aplastic anemia in the past two decades. Clin Infect Dis. 2011 Mar 15;52(6):726-35. doi: 10.1093/cid/ciq245.

  PMID: 21367725 BACKGROUND

• Peffault de Latour R, Kulasekararaj A, Iacobelli S, Terwel SR, Cook R, Griffin M, Halkes CJM, Recher C, Barraco F, Forcade E, Vallejo JC, Drexler B, Mear JB, Smith AE, Angelucci E, Raymakers RAP, de Groot MR, Daguindau E, Nur E, Barcellini W, Russell NH, Terriou L, Iori AP, La Rocca U, Sureda A, Sanchez-Ortega I, Xicoy B, Jarque I, Cavenagh J, Sicre de Fontbrune F, Marotta S, Munir T, Tjon JML, Tavitian S, Praire A, Clement L, Rabian F, Marano L, Hill A, Palmisani E, Muus P, Cacace F, Frieri C, van Lint MT, Passweg JR, Marsh JCW, Socie G, Mufti GJ, Dufour C, Risitano AM; Severe Aplastic Anemia Working Party of the European Society for Blood and Marrow Transplantation. Eltrombopag Added to Immunosuppression in Severe Aplastic Anemia. N Engl J Med. 2022 Jan 6;386(1):11-23. doi: 10.1056/NEJMoa2109965.

  PMID: 34986284 BACKGROUND

• Kulasekararaj A, Cavenagh J, Dokal I, Foukaneli T, Gandhi S, Garg M, Griffin M, Hillmen P, Ireland R, Killick S, Mansour S, Mufti G, Potter V, Snowden J, Stanworth S, Zuha R, Marsh J; BSH Committee. Guidelines for the diagnosis and management of adult aplastic anaemia: A British Society for Haematology Guideline. Br J Haematol. 2024 Mar;204(3):784-804. doi: 10.1111/bjh.19236. Epub 2024 Jan 21.

  PMID: 38247114 BACKGROUND

Related Links

• Efficacy and Safety Study of Umbilical Cord Blood Transplantation (UCBT) with Total Marrow Irradiation (TMI)-Based Conditioning Regimen for Adults with Refractory/Relapsed Aplastic Anemia (AA)

MeSH Terms

Conditions

Anemia, Aplastic; Recurrence

Interventions

fludarabine; Melphalan; Honey

Condition Hierarchy (Ancestors)

Anemia; Hematologic Diseases; Hemic and Lymphatic Diseases; Bone Marrow Failure Disorders; Bone Marrow Diseases; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phenylalanine; Amino Acids, Aromatic; Amino Acids, Cyclic; Amino Acids; Amino Acids, Peptides, and Proteins; Food; Diet, Food, and Nutrition; Physiological Phenomena; Food and Beverages

Study Officials

• Zimin Sun

  IH & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Zimin Sun

CONTACT

86-22-23909492; sunzimin@ihcams.ac.cn

Zimin Sun

CONTACT

13605518126; sunzimin@ihcams.ac.cn

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: Principal Investigator

Study Record Dates

• First Submitted: July 12, 2025
• First Posted: July 22, 2025
• Study Start: July 20, 2025
• Primary Completion (Estimated): January 1, 2028
• Study Completion (Estimated): June 1, 2028
• Last Updated: July 22, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR, ANALYTIC CODE
• Time Frame: start date: June 2028 end date: june 2030
• Access Criteria: the users of "ClinicalTrail.gov"

Locations

CN (1)