Aplastic Anemia IdiopathicPhase 2TMINCT07078721
Efficacy and Safety of UCBT With TMI -Based Conditioning Regimen for Adults With Refractory/Relapsed Aplastic Anemia
A Phase 2 study testing Total Marrow Irradiation, Fludarabine (FLU) and Melphalan (Mel) in people with Aplastic Anemia Idiopathic, run by Institute of Hematology & Blood Diseases Hospital, China at 1 site in China.
Trial 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). Read more about this study
- Who is it for?
- Ages 18 to 50 years
- Conditions the study is for
- Aplastic Anemia Idiopathic
- What is being tested?
- Total Marrow Irradiation, Fludarabine (FLU) and Melphalan (Mel)
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 11 participants
- Where
- 1 siteChina
- Study dates
- 20 Jul 2025to Jun 2028
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
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 50 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- 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:
Show all 14Show fewer
- 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.
Who cannot join
- 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.
Show all 11Show fewer
- 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.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
China1 site
Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College
Tianjin, City, 300020
Zimin Sun, 86-22-23909492, sunzimin@ihcams.ac.cn
Yuan Li, 86-22-23909492, liyuan@ihcams.ac.cn
About this study
Official title: 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).
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.
Read the detailed description
Refractory/relapsed aplastic anemia (AA) in adults remains a clinical challenge that is frequently encountered and urgently needs to be resolved. Refractory AA is ineffective to the standard first-line treatment regimen, which is based on antithymocyte globulin (ATG) combined with cyclosporine A (CsA) as the standard immunosuppressive therapy (IST), accounting for approximately 30%-40% of all AA patients. It has been reported that the 5-year mortality rate of refractory severe aplastic anemia (r-SAA) exceeds 40% after diagnosis. Brosdky et al. reported that the 10-year event-free survival (EFS) of SAA treated with high-dose cyclophosphamide-based IST is only 28%. The efficacy is not satisfactory. Thrombopoietin receptor agonists such as eltrombopag, as an important treatment for r-SAA, have a hematologic response rate of only 41.8% with monotherapy for 52 weeks, with an overall low response rate and unsatisfactory quality of response. The 24-week complete blood count response is only 16.4%, and the 52-week response is only 21.8%. Clonal hematopoiesis is also a long-term concern for IST. Multiple centers have reported that the early efficacy of IST combined with thrombopoietin receptor agonists for treating SAA has improved, but the long-term overall efficacy has not substantially exceeded that of IST alone. The bone marrow failure of non-severe aplastic anemia (NSAA) is less severe than that of SAA, and the main treatment methods are IST ± thrombopoietin receptor agonists or combined with androgens, similar to SAA, with similar long-term efficacy challenges. Therefore, the development of new and effective treatment methods is an urgent clinical need.
Refractory AA is ineffective to IST, possibly mainly due to the insufficient number or functional abnormalities of residual hematopoietic stem/progenitor cells in patients. Therefore, salvage treatment should prioritize hematopoietic stem cell transplantation (HSCT) to supplement normal hematopoietic stem cells and rebuild hematopoiesis. According to domestic and international guidelines for the diagnosis and treatment of adult AA, unrelated donor allogeneic hematopoietic stem cell transplantation or haploidentical hematopoietic stem cell transplantation are the main salvage treatment methods for refractory SAA, with hematopoietic stem cells mainly derived from peripheral blood or bone marrow. However, the availability of suitable donors is one of the main difficulties for unrelated donor allogeneic hematopoietic stem cell transplantation or haploidentical hematopoietic stem cell transplantation. Many AA patients cannot receive early treatment due to the lack of suitable hematopoietic stem cell donors and have to wait for a long time. 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. However, Delatour et al. reported that the 3-year overall survival (OS) of patients with refractory AA treated with cord blood transplantation is only 38% ± 6%, with unsatisfactory efficacy. Nevertheless, with the optimization of conditioning regimens, the popularization of high-resolution HLA typing, and the continuous improvement of supportive care, the efficacy of unrelated cord blood transplantation (UCBT) is expected to improve.
The optimization of the conditioning regimen for UCBT is a crucial factor in determining patient outcomes. Hiramoto et al. reported that patients received conditioning regimens of total body irradiation (TBI) (≤4Gy) combined with fludarabine/melphalan (Flu/Mel) or fludarabine/cyclophosphamide (Flu/Cy). The results showed that a radiation dose of 4 Gy is an independent influencing factor for neutrophil engraftment. Compared with the Flu/Cy group, a higher proportion of patients in the Flu/Mel group received 4 Gy (96% vs. 68%, p<0.01), but there was no difference in engraftment success rates (77.8% vs. 72%). Compared with TBI, TMI has many advantages: (1) TMI clears residual T cells in the recipient's body, optimizes spatial competition, and better prepares the bone marrow niche for cord blood stem cells; (2) It can more accurately target the bone marrow region; (3) It reduces toxicity to other organs and can better protect the patient's organ function; (4) It reduces the risk of long-term tumors; (5) It lowers the radiation dose: the TMI dose is 4-6 Gy, while the TBI dose reaches 12 Gy; (6) TMI is applicable to a wider range of people and is more tolerable for elderly/weak patients. Therefore, TMI has potential advantages in the conditioning regimen for refractory/relapsed severe aplastic anemia.
Therefore, we have designed and proposed for the first time the Phase II clinical study titled "A Phase II Study on the Efficacy and Safety of Umbilical Cord Blood Transplantation (UCBT) with a Total Marrow Irradiation (TMI)-Based Conditioning Regimen for the Treatment of Refractory/Relapsed Aplastic Anemia (AA) in Adults." This study employs a TMI (4 Gy)/Flu/Mel conditioning regimen and single-unit cord blood stem cell transplantation to treat adult refractory/relapsed AA, aiming to evaluate the efficacy and safety of this regimen.
- Conditions
- Aplastic Anemia Idiopathic
- Being tested
- Total Marrow Irradiation, Fludarabine (FLU), Melphalan (Mel)
- Keywords
- aplastic anemia, refractory/relapsed, Total Marrow Irradiation, Umbilical Cord Blood Transplantation
- Medical subject headings
- Anemia, Aplastic, Recurrence
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Total Marrow IrradiationRadiation
Also called Marrow-Targeted Radiotherapy, Organ-Sparing Marrow-Targeted Irradiation (OSMI)
- TMI 4 Gy qd on Day -2;
Fludarabine (FLU)Drug
Also called FaraA
Flu 30 mg/m² × 5 days on Days -6, -5, -4, -3, -2;
Melphalan (Mel)Drug
Also called L-PAM
Mel 100 mg/m² qd on Day -1.
| Study group | Role | What they receive |
|---|---|---|
| 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) Receives: Radiation: Total Marrow Irradiation; Drug: Fludarabine (FLU); Drug: Melphalan (Mel) |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: ---Enrollment Period (2 weeks)---Treatment Period (7 days)---Follow-Up Period (12 months)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Jul 2025
- Study start20 Jul 2025 (estimated)
- Primary completionJan 2028 (estimated)
- Study completionJun 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (10)Papers the sponsor has linked to this study.
- Other trials for Aplastic Anemia IdiopathicStudies of the same condition, open and under way.
- More trials run by Institute of Hematology & Blood Diseases Hospital, ChinaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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
- 11 participants (estimated)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, SunZimin, Institute of Hematology & Blood Diseases Hospital, China
- Investigators
- Zimin Sun, Principal investigator, IH & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07078721
- Sponsor's protocol ID
- IIT2025071
- Acronym
- TMI
- Status last verified
- Jul 2025
- First submitted
- 12 Jul 2025
- Last updated
- 22 Jul 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: 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.
Publications
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.
PubMed 22762314Jagasia 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.
PubMed 25529383Harris 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.
PubMed 26386318Kurtzberg 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.
PubMed 36718114Hiramoto 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.
PubMed 34546409Peffault 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.
PubMed 20561593Red 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.
PubMed 36709177Valdez 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.
PubMed 21367725Peffault 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.
PubMed 34986284Kulasekararaj 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.
PubMed 38247114
Study at a glance
From the registry record, last updated by the sponsor on 22 Jul 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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).
- ClinicalTrials.gov ID
- NCT07078721
- Acronym / sponsor ID
- TMI / IIT2025071
- Conditions
- Aplastic Anemia Idiopathic
- Keywords
- aplastic anemia, refractory/relapsed, Total Marrow Irradiation, Umbilical Cord Blood Transplantation
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 11 participants (estimated)
- Lead sponsor
- Institute of Hematology & Blood Diseases Hospital, ChinaUniversity, hospital or other
- Study start
- 20 Jul 2025 (estimated)
- Primary completion
- Jan 2028 (estimated)
- Study completion
- Jun 2028 (estimated)
- First posted
- 22 Jul 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
Refractory/relapsed aplastic anemia (AA) in adults remains a clinical challenge that is frequently encountered and urgently needs to be resolved. Refractory AA is ineffective to the standard first-line treatment regimen, which is based on antithymocyte globulin (ATG) combined with cyclosporine A (CsA) as the standard immunosuppressive therapy (IST), accounting for approximately 30%-40% of all AA patients. It has been reported that the 5-year mortality rate of refractory severe aplastic anemia (r-SAA) exceeds 40% after diagnosis. Brosdky et al. reported that the 10-year event-free survival (EFS) of SAA treated with high-dose cyclophosphamide-based IST is only 28%. The efficacy is not satisfactory. Thrombopoietin receptor agonists such as eltrombopag, as an important treatment for r-SAA, have a hematologic response rate of only 41.8% with monotherapy for 52 weeks, with an overall low response rate and unsatisfactory quality of response. The 24-week complete blood count response is only 16.4%, and the 52-week response is only 21.8%. Clonal hematopoiesis is also a long-term concern for IST. Multiple centers have reported that the early efficacy of IST combined with thrombopoietin receptor agonists for treating SAA has improved, but the long-term overall efficacy has not substantially exceeded that of IST alone. The bone marrow failure of non-severe aplastic anemia (NSAA) is less severe than that of SAA, and the main treatment methods are IST ± thrombopoietin receptor agonists or combined with androgens, similar to SAA, with similar long-term efficacy challenges. Therefore, the development of new and effective treatment methods is an urgent clinical need.
Refractory AA is ineffective to IST, possibly mainly due to the insufficient number or functional abnormalities of residual hematopoietic stem/progenitor cells in patients. Therefore, salvage treatment should prioritize hematopoietic stem cell transplantation (HSCT) to supplement normal hematopoietic stem cells and rebuild hematopoiesis. According to domestic and international guidelines for the diagnosis and treatment of adult AA, unrelated donor allogeneic hematopoietic stem cell transplantation or haploidentical hematopoietic stem cell transplantation are the main salvage treatment methods for refractory SAA, with hematopoietic stem cells mainly derived from peripheral blood or bone marrow. However, the availability of suitable donors is one of the main difficulties for unrelated donor allogeneic hematopoietic stem cell transplantation or haploidentical hematopoietic stem cell transplantation. Many AA patients cannot receive early treatment due to the lack of suitable hematopoietic stem cell donors and have to wait for a long time. 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. However, Delatour et al. reported that the 3-year overall survival (OS) of patients with refractory AA treated with cord blood transplantation is only 38% ± 6%, with unsatisfactory efficacy. Nevertheless, with the optimization of conditioning regimens, the popularization of high-resolution HLA typing, and the continuous improvement of supportive care, the efficacy of unrelated cord blood transplantation (UCBT) is expected to improve.
The optimization of the conditioning regimen for UCBT is a crucial factor in determining patient outcomes. Hiramoto et al. reported that patients received conditioning regimens of total body irradiation (TBI) (≤4Gy) combined with fludarabine/melphalan (Flu/Mel) or fludarabine/cyclophosphamide (Flu/Cy). The results showed that a radiation dose of 4 Gy is an independent influencing factor for neutrophil engraftment. Compared with the Flu/Cy group, a higher proportion of patients in the Flu/Mel group received 4 Gy (96% vs. 68%, p<0.01), but there was no difference in engraftment success rates (77.8% vs. 72%). Compared with TBI, TMI has many advantages: (1) TMI clears residual T cells in the recipient's body, optimizes spatial competition, and better prepares the bone marrow niche for cord blood stem cells; (2) It can more accurately target the bone marrow region; (3) It reduces toxicity to other organs and can better protect the patient's organ function; (4) It reduces the risk of long-term tumors; (5) It lowers the radiation dose: the TMI dose is 4-6 Gy, while the TBI dose reaches 12 Gy; (6) TMI is applicable to a wider range of people and is more tolerable for elderly/weak patients. Therefore, TMI has potential advantages in the conditioning regimen for refractory/relapsed severe aplastic anemia.
Therefore, we have designed and proposed for the first time the Phase II clinical study titled "A Phase II Study on the Efficacy and Safety of Umbilical Cord Blood Transplantation (UCBT) with a Total Marrow Irradiation (TMI)-Based Conditioning Regimen for the Treatment of Refractory/Relapsed Aplastic Anemia (AA) in Adults." This study employs a TMI (4 Gy)/Flu/Mel conditioning regimen and single-unit cord blood stem cell transplantation to treat adult refractory/relapsed AA, aiming to evaluate the efficacy and safety of this regimen.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| TMI in AA | Experimental | Radiation: Total Marrow Irradiation, Drug: Fludarabine (FLU), Drug: Melphalan (Mel)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) |
Who may qualify
- Ages
- 18 to 50 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (14 listed)
- Subjects suitable for enrollment in this study must meet all of the following criteria:
- Peripheral blood criteria
- 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.
Key exclusion criteria (11 listed)
- Subjects with any of the following conditions are not eligible for enrollment in this study:
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Total Marrow IrradiationAlso: Marrow-Targeted Radiotherapy, Organ-Sparing Marrow-Targeted Irradiation (OSMI)- TMI 4 Gy qd on Day -2; | Radiation | TMI in AA |
| Fludarabine (FLU)Also: FaraAFlu 30 mg/m² × 5 days on Days -6, -5, -4, -3, -2; | Drug | TMI in AA |
| Melphalan (Mel)Also: L-PAMMel 100 mg/m² qd on Day -1. | Drug | TMI in AA |
Primary outcome
Event-free survival (EFS) at 12 months post-transplant.
Time frame: ---Enrollment Period (2 weeks)---Treatment Period (7 days)---Follow-Up Period (12 months)
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.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Jul 2025.
- Background: PubMed 22762314Olnes 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.
- Background: PubMed 25529383Jagasia 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.
- Background: PubMed 26386318Harris 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.
- Background: PubMed 36718114Kurtzberg 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.
- Background: PubMed 34546409Hiramoto 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.
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- 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)Link provided by the sponsor.
- Individual participant dataSharing planned: Yes. 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Zimin Sun principal investigator
IH & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Total Marrow Irradiation, Fludarabine (FLU) and Melphalan (Mel) in people with Aplastic Anemia Idiopathic, run by Institute of Hematology & Blood Diseases Hospital, China 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 14 inclusion and 11 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: opening soon, as of the sponsor's last update on 22 Jul 2025. 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?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Zimin Sun (86-22-23909492, sunzimin@ihcams.ac.cn), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Event-free survival (EFS) at 12 months post-transplant. (time frame: ---Enrollment Period (2 weeks)---Treatment Period (7 days)---Follow-Up Period (12 months)). 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 NCT07078721, which also lists 10 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 22 Jul 2025.