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Clinical Trial Details — Status: Not yet recruiting

Administrative data

NCT number NCT06111612
Other study ID # SHSYXY-202308-THI-BFA
Secondary ID
Status Not yet recruiting
Phase
First received
Last updated
Start date January 1, 2024
Est. completion date January 1, 2027

Study information

Verified date November 2023
Source Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine
Contact Xianmin Song, MD
Phone +86 13501672508
Email shongxm@139.com
Is FDA regulated No
Health authority
Study type Observational

Clinical Trial Summary

This study is a multicenter, single-arm, prospective phase II clinical trial that evaluates the efficacy and safety of an intensive conditioning regimen with thiotepa combined with busulfan, fludarabine, and cytarabine for allogeneic hematopoietic stem cell transplantation in the treatment of myeloid malignancies with extramedullary involvement. The conditioning regimen includes thiotepa at a dose of 5mg/kg/d from d -9 to d -8 (2 days), fludarabine at 30mg/m2/d from d -7 to d -3 (5 days), cytarabine at 1-1.5g/m2/d from d -7 to d -3 (5 days), and busulfan at 3.2mg/kg/d from d -5 to d -3 (3 days). Conditioning begins on day -9, and donor hematopoietic stem cell infusion is performed on day 0. All patients will undergo bone marrow examination on day 14 and day 28 post-transplant, followed by bone marrow examinations every 30 days within the first year after transplantation, and every 60 days within the second year after transplantation. If disease relapse is suspected during the follow-up period, bone marrow or extramedullary relapse site examinations will be conducted at any time. The primary study endpoints are the 1-year and 2-year progression-free survival (PFS) rates post-transplant. Secondary study endpoints include the incidence of acute graft-versus-host disease (GVHD) within 180 days post-transplant, cumulative relapse rates at 1 year and 2 years post-transplant, 1-year and 2-year overall survival (OS), graft-versus-host disease-free, relapse-free survival (GRFS), non-relapse mortality (NRM), cumulative incidence of chronic GVHD, and the incidence of Cytomegalovirus (CMV)and Epstein-Barr virus(EBV)reactivation within 1 year.


Recruitment information / eligibility

Status Not yet recruiting
Enrollment 50
Est. completion date January 1, 2027
Est. primary completion date January 1, 2026
Accepts healthy volunteers No
Gender All
Age group 18 Years to 55 Years
Eligibility Inclusion Criteria: 1. Age between 18 and less than 55 years, regardless of gender. 2. Criteria for myeloid tumors with extramedullary involvement: 1. AML (Acute Myeloid Leukemia) with at least one extramedullary lesion achieving hematological remission (CR1 or CR2) after induction therapy. 2. MDS (Myelodysplastic Syndrome) with at least one extramedullary lesion and bone marrow blast percentage = 5% achieving hematological CR after treatment; CMML (Chronic Myelomonocytic Leukemia) with at least one extramedullary lesion (diagnosed according to WHO standards) achieving hematological CR after treatment. 3. Control and remission of extramedullary lesions, including those in the central nervous system, testes, skin, and other extramedullary tissues. 4. Granulocytic sarcoma with or without bone marrow involvement, and achieving remission after treatment. 3. Patients must have a suitable hematopoietic stem cell donor: 1. Related donors must have at least 5/10 matches for HLA-A, -B, -C, -DQB1, and - DRB1. 2. Unrelated donors must have at least 8/10 matches for HLA-A, -B, -C, -DQB1, and - DRB1. 4. Hematopoietic cell transplantation comorbidity index (HCT-CI) score = 2. 5. ECOG (Eastern Cooperative Oncology Group) performance status: 0-2. 6. Adequate liver, kidney, and cardiopulmonary function, meeting the following requirements: 1. Serum creatinine = 1.5x ULN (the upper limit of normal). 2. Cardiac function: Ejection fraction = 50%. 3. Baseline oxygen saturation > 92%. 4. Total bilirubin = 1.5 x ULN; ALT and AST = 2.0 x ULN. 5. Pulmonary function: DLCO (corrected for hemoglobin) = 40% and FEV1 (Forced Expiratory Volume in 1 second) = 50%. 7. Patients must have the ability to understand and be willing to participate in this study and sign an informed consent form. Exclusion Criteria: 1. History of malignancies other than myeloid tumors within the 5 years prior to screening, except for adequately treated in situ cervical cancer, basal cell carcinoma, squamous cell carcinoma of the skin, and curatively treated localized prostate cancer or ductal carcinoma in situ. 2. ECOG > 2. 3. HCT-CI score = 3. 4. Any unstable systemic diseases, including but not limited to unstable angina, recent cerebrovascular accidents or transient ischemic attacks within the 3 months prior to screening, myocardial infarction within the 3 months prior to screening, congestive heart failure (New York Heart Association [NYHA] class = III), severe arrhythmias requiring drug treatment after pacemaker implantation, significant liver, kidney, or metabolic diseases, and pulmonary arterial hypertension. 5. Active, uncontrolled infections, including those associated with hemodynamic instability, new or worsening infection symptoms or signs, new infectious lesions on imaging, or persistent unexplained fever without signs or symptoms of infection. 6. Conditions requiring treatment such as grade 2 or higher seizures, paralysis, aphasia, recent severe cerebral infarction, severe traumatic brain injury, dementia, Parkinson's disease, or schizophrenia. 7. HIV-infected individuals. 8. Active hepatitis B (HBV) or active hepatitis C (HCV) requiring antiviral therapy. Patients at risk of HBV reactivation, are defined as those who are positive for hepatitis B surface antigen or core antibody without receiving antiviral therapy. 9. Pregnant or breastfeeding women. 10. Fertile males and females unwilling to use contraception during the treatment period and for 12 months after treatment.

Study Design


Related Conditions & MeSH terms


Locations

Country Name City State
n/a

Sponsors (1)

Lead Sponsor Collaborator
Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine

References & Publications (18)

Alatrash G, de Lima M, Hamerschlak N, Pelosini M, Wang X, Xiao L, Kerbauy F, Chiattone A, Rondon G, Qazilbash MH, Giralt SA, de Padua Silva L, Hosing C, Kebriaei P, Zhang W, Nieto Y, Saliba RM, Champlin RE, Andersson BS. Myeloablative reduced-toxicity i.v. busulfan-fludarabine and allogeneic hematopoietic stem cell transplant for patients with acute myeloid leukemia or myelodysplastic syndrome in the sixth through eighth decades of life. Biol Blood Marrow Transplant. 2011 Oct;17(10):1490-6. doi: 10.1016/j.bbmt.2011.02.007. Epub 2011 Feb 18. — View Citation

Bakst RL, Tallman MS, Douer D, Yahalom J. How I treat extramedullary acute myeloid leukemia. Blood. 2011 Oct 6;118(14):3785-93. doi: 10.1182/blood-2011-04-347229. Epub 2011 Jul 27. — View Citation

Bruserud O, Reikvam H, Kittang AO, Ahmed AB, Tvedt TH, Sjo M, Hatfield KJ. High-dose etoposide in allogeneic stem cell transplantation. Cancer Chemother Pharmacol. 2012 Dec;70(6):765-82. doi: 10.1007/s00280-012-1990-z. Epub 2012 Oct 6. — View Citation

Cankaya H, Ugras S, Dilek I. Head and neck granulocytic sarcoma with acute myeloid leukemia: three rare cases. Ear Nose Throat J. 2001 Apr;80(4):224-6, 228-9. — View Citation

Chevallier P, Mohty M, Lioure B, Michel G, Contentin N, Deconinck E, Bordigoni P, Vernant JP, Hunault M, Vigouroux S, Blaise D, Tabrizi R, Buzyn A, Socie G, Michallet M, Volteau C, Harousseau JL. Allogeneic hematopoietic stem-cell transplantation for myeloid sarcoma: a retrospective study from the SFGM-TC. J Clin Oncol. 2008 Oct 20;26(30):4940-3. doi: 10.1200/JCO.2007.15.6315. Epub 2008 Jul 7. — View Citation

Clift RA, Buckner CD, Appelbaum FR, Sullivan KM, Storb R, Thomas ED. Long-term follow-Up of a randomized trial of two irradiation regimens for patients receiving allogeneic marrow transplants during first remission of acute myeloid leukemia. Blood. 1998 Aug 15;92(4):1455-6. No abstract available. — View Citation

Cribe AS, Steenhof M, Marcher CW, Petersen H, Frederiksen H, Friis LS. Extramedullary disease in patients with acute myeloid leukemia assessed by 18F-FDG PET. Eur J Haematol. 2013 Apr;90(4):273-8. doi: 10.1111/ejh.12085. — View Citation

Down JD, Westerhof GR, Boudewijn A, Setroikromo R, Ploemacher RE. Thiotepa improves allogeneic bone marrow engraftment without enhancing stem cell depletion in irradiated mice. Bone Marrow Transplant. 1998 Feb;21(4):327-30. doi: 10.1038/sj.bmt.1701103. — View Citation

Elenitoba-Johnson K, Hodges GF, King TC, Wu CD, Medeiros LJ. Extramedullary myeloid cell tumors arising in the setting of chronic myelomonocytic leukemia. A report of two cases. Arch Pathol Lab Med. 1996 Jan;120(1):62-7. — View Citation

Hancock JC, Prchal JT, Bennett JM, Listinsky CM. Trilineage extramedullary myeloid cell tumor in myelodysplastic syndrome. Arch Pathol Lab Med. 1997 May;121(5):520-3. — View Citation

Li C, Mathews V, Kim S, George B, Hebert K, Jiang H, Li C, Zhu Y, Keesler DA, Boelens JJ, Dvorak CC, Agarwal R, Auletta JJ, Goyal RK, Hanna R, Kasow K, Shenoy S, Smith AR, Walters MC, Eapen M. Related and unrelated donor transplantation for beta-thalassemia major: results of an international survey. Blood Adv. 2019 Sep 10;3(17):2562-2570. doi: 10.1182/bloodadvances.2019000291. — View Citation

Martin-Subero JI. Predicting leukemia relapse. Nat Med. 2018 Apr 10;24(4):385-387. doi: 10.1038/nm.4529. No abstract available. — View Citation

Michel G, Boulad F, Small TN, Black P, Heller G, Castro-Malaspina H, Childs BH, Gillio AP, Papadopoulos EB, Young JW, Kernan NA, O'Reilly RJ. Risk of extramedullary relapse following allogeneic bone marrow transplantation for acute myelogenous leukemia with leukemia cutis. Bone Marrow Transplant. 1997 Jul;20(2):107-12. doi: 10.1038/sj.bmt.1700857. — View Citation

Pileri SA, Ascani S, Cox MC, Campidelli C, Bacci F, Piccioli M, Piccaluga PP, Agostinelli C, Asioli S, Novero D, Bisceglia M, Ponzoni M, Gentile A, Rinaldi P, Franco V, Vincelli D, Pileri A Jr, Gasbarra R, Falini B, Zinzani PL, Baccarani M. Myeloid sarcoma: clinico-pathologic, phenotypic and cytogenetic analysis of 92 adult patients. Leukemia. 2007 Feb;21(2):340-50. doi: 10.1038/sj.leu.2404491. Epub 2006 Dec 14. — View Citation

Pui CH, Kalwinsky DK, Schell MJ, Mason CA, Mirro J Jr, Dahl GV. Acute nonlymphoblastic leukemia in infants: clinical presentation and outcome. J Clin Oncol. 1988 Jun;6(6):1008-13. doi: 10.1200/JCO.1988.6.6.1008. — View Citation

Sanders S, Chua N, Larouche JF, Owen C, Shafey M, Stewart DA. Outcomes of Consecutively Diagnosed Primary Central Nervous System Lymphoma Patients Using the Alberta Lymphoma Clinical Practice Guideline Incorporating Thiotepa-Busulfan Conditioning for Transplantation-Eligible Patients. Biol Blood Marrow Transplant. 2019 Aug;25(8):1505-1510. doi: 10.1016/j.bbmt.2019.04.004. Epub 2019 Apr 6. — View Citation

Sora F, Grazia CD, Chiusolo P, Raiola AM, Bregante S, Mordini N, Olivieri A, Iori AP, Patriarca F, Grisariu S, Terruzzi E, Rambaldi A, Sica S, Bruno B, Angelucci E, Bacigalupo A. Allogeneic Hemopoietic Stem Cell Transplants in Patients with Acute Myeloid Leukemia (AML) Prepared with Busulfan and Fludarabine (BUFLU) or Thiotepa, Busulfan, and Fludarabine (TBF): A Retrospective Study. Biol Blood Marrow Transplant. 2020 Apr;26(4):698-703. doi: 10.1016/j.bbmt.2019.12.725. Epub 2019 Dec 23. — View Citation

Su WP. Clinical, histopathologic, and immunohistochemical correlations in leukemia cutis. Semin Dermatol. 1994 Sep;13(3):223-30. — View Citation

* Note: There are 18 references in allClick here to view all references

Outcome

Type Measure Description Time frame Safety issue
Primary 1y and 2y-PFS 1-year and 2-year progression-free survival (PFS) rates post-transplant 2023-2027
Secondary aGVHD acute graft-versus-host disease (GVHD) within 180 days post-transplant 2023-2025
Secondary 1y and 2y-CIR cumulative relapse rates (CIR) at 1 year and 2 years post-transplant 2023-2027
Secondary 1y and 2y-OS overall survival (OS) at 1 year and 2 years post-transplant 2023-2027
Secondary GRFS graft-versus-host disease-free, relapse-free survival (GRFS) at 2 years post-transplant 2023-2027
Secondary NRM non-relapse mortality (NRM) at 2 years post-transplant 2023-2027
Secondary cGVHD cumulative incidence of chronic GVHD at 2 years post-transplant 2023-2027
Secondary CMV and EBV reactivation the incidence of CMV and EBV reactivation within 1 year 2023-2026
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