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This study is a single-center, single-arm, prospective phase II clinical trial that evaluates the efficacy and safety of an reduced-intensity conditioning (RIC) regimen with thiotepa combined with busulfan, fludarabine, and cytarabine for allogeneic hematopoietic stem cell transplantation in the treatment of relapse and refratory peripheral T-cells lymphoma. The conditioning regimen includes thiotepa at a dose of 5mg/kg/d at d -7 (1 day), fludarabine at 30mg/m2/d from d -6 to d -2 (5 days), cytarabine at 1g/m2/d from d -6 to d -2 (5 days), and busulfan at 3.2mg/kg/d from d -4 to d -3 (2 days). Conditioning begins on day -7, 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. FDG-PET/CT imaging will be adopted every 6 months after transplantation. If disease relapse is suspected during the follow-up period, bone marrow and 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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| intervention arm | Experimental | Participants will receive allogenetic hematopoietic stem cell transplantation (allo-HSCT) with the reduced intensity conditioning regimen including thiotepa(5mg / kg / d-7d ( 1d )), fludarabine (30mg / m2 / d, -6d--2d ( 5d )), Ara-C (1g / m2 / d, -6d--2d ( 5d )), and busulfan(3.2mg / kg / d, -4d-3d ( 2d )). |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Thiotepa | Drug | The reduced intensity conditioning regimen is composed by thiotepa (5mg / kg / d-7d (1d)), fludarabine (30mg / m2 / d, -6d--2d (5d)), Ara-C (1g / m2 / d, -6d--2d (5d)), and busulfan (3.2mg / kg / d, -4d-3d (2d)). |
| Measure | Description | Time Frame |
|---|---|---|
| 1y and 2y-progression-free survival (PFS) | 1-year and 2-year progression-free survival (PFS) rates post-transplant | up to 1 years for the 1y-PFS and up to 2 years for the 2y-PFS |
| Measure | Description | Time Frame |
|---|---|---|
| acute graft-versus-host disease (aGVHD) | acute graft-versus-host disease (aGVHD) within 180 days post-transplant | up to 180 days |
| 1y and 2y-cumulative relapse rates (CIR) | cumulative relapse rates (CIR) at 1 year and 2 years post-transplant |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| xianmin Song, MD | Contact | +86 1350167250 | shongxm@139.com |
| Name | Affiliation | Role |
|---|---|---|
| Xianmin Song, MD | Shanghai General HospitalShanghai General Hospital, Shanghai Jiao Tong University School of Medicine | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Shanghai General Hospital | Recruiting | Shanghai | Shanghai Municipality | 200080 | China |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 29661730 | Background | Cao C, Feng J, Gu H, Tang H, Xu L, Dong H, Dong B, Shu M, Bai Q, Liang R, Zhang T, Yang L, Wang Z, Chen X, Gao G. Distribution of lymphoid neoplasms in Northwest China: Analysis of 3244 cases according to WHO classification in a single institution. Ann Diagn Pathol. 2018 Jun;34:60-65. doi: 10.1016/j.anndiagpath.2017.05.005. Epub 2017 May 12. | |
| 21854649 |
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| ID | Term |
|---|---|
| D016411 | Lymphoma, T-Cell, Peripheral |
| ID | Term |
|---|---|
| D016399 | Lymphoma, T-Cell |
| D008228 | Lymphoma, Non-Hodgkin |
| D008223 | Lymphoma |
| D009370 | Neoplasms by Histologic Type |
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Not provided
| ID | Term |
|---|---|
| D013852 | Thiotepa |
| C024352 | fludarabine |
| D002066 | Busulfan |
| D003561 | Cytarabine |
| ID | Term |
|---|---|
| D063088 | Phosphoramides |
| D009943 | Organophosphorus Compounds |
| D009930 | Organic Chemicals |
| D013721 | Triethylenephosphoramide |
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|
| up to 1 years for the 1y-CIR and up to 2 years for the 2y-CIR |
| 1y and 2y-overall survival (OS) | overall survival (OS) at 1 year and 2 years post-transplant | up to 1 years for the 1y-OS and up to 2 years for the 2y-OS |
| graft-versus-host disease-free, relapse-free survival (GRFS) | graft-versus-host disease-free, relapse-free survival (GRFS) at 2 years post-transplant | up to 2 years |
| non-relapse mortality (NRM) | non-relapse mortality (NRM) at 2 years post-transplant | up to 2 years |
| cumulative incidence of chronic GVHD | cumulative incidence of chronic GVHD at 2 years post-transplant | up to 2 years |
| CMV and EBV reactivation | the incidence of CMV and EBV reactivation within 1 year | up to 1 year |
| Yang QP, Zhang WY, Yu JB, Zhao S, Xu H, Wang WY, Bi CF, Zuo Z, Wang XQ, Huang J, Dai L, Liu WP. Subtype distribution of lymphomas in Southwest China: analysis of 6,382 cases using WHO classification in a single institution. Diagn Pathol. 2011 Aug 22;6:77. doi: 10.1186/1746-1596-6-77. |
| 18626005 | Background | Vose J, Armitage J, Weisenburger D; International T-Cell Lymphoma Project. International peripheral T-cell and natural killer/T-cell lymphoma study: pathology findings and clinical outcomes. J Clin Oncol. 2008 Sep 1;26(25):4124-30. doi: 10.1200/JCO.2008.16.4558. Epub 2008 Jul 14. |
| 30511217 | Background | Liu X, Yang M, Wu M, Zheng W, Xie Y, Zhu J, Song Y, Liu W. A retrospective study of the CHOP, CHOPE, and CHOPE/G regimens as the first-line treatment of peripheral T-cell lymphomas. Cancer Chemother Pharmacol. 2019 Mar;83(3):443-449. doi: 10.1007/s00280-018-3744-z. Epub 2018 Dec 3. |
| 31065733 | Background | Janikova A, Chloupkova R, Campr V, Klener P, Hamouzova J, Belada D, Prochazka V, Pytlik R, Pirnos J, Duras J, Mocikova H, Bortlicek Z, Kopalova N, Mayer J, Trneny M. First-line therapy for T cell lymphomas: a retrospective population-based analysis of 906 T cell lymphoma patients. Ann Hematol. 2019 Aug;98(8):1961-1972. doi: 10.1007/s00277-019-03694-y. Epub 2019 May 8. |
| 37711206 | Background | Couto SCF, Kowes A, Aurabi CS, Oliveira TGM, Klinger P, Rocha V. Autologous, allogeneic hematopoietic cell transplantation and CAR-T/NK therapy: what is their real importance in PTCL? Front Oncol. 2023 Aug 30;13:1195759. doi: 10.3389/fonc.2023.1195759. eCollection 2023. |
| 14630683 | Background | Rodriguez J, Caballero MD, Gutierrez A, Marin J, Lahuerta JJ, Sureda A, Carreras E, Leon A, Arranz R, Fernandez de Sevilla A, Zuazu J, Garcia-Larana J, Rifon J, Varela R, Gandarillas M, SanMiguel J, Conde E. High-dose chemotherapy and autologous stem cell transplantation in peripheral T-cell lymphoma: the GEL-TAMO experience. Ann Oncol. 2003 Dec;14(12):1768-75. doi: 10.1093/annonc/mdg459. |
| 29599200 | Background | Bellei M, Foss FM, Shustov AR, Horwitz SM, Marcheselli L, Kim WS, Cabrera ME, Dlouhy I, Nagler A, Advani RH, Pesce EA, Ko YH, Martinez V, Montoto S, Chiattone C, Moskowitz A, Spina M, Biasoli I, Manni M, Federico M; International T-cell Project Network. The outcome of peripheral T-cell lymphoma patients failing first-line therapy: a report from the prospective, International T-Cell Project. Haematologica. 2018 Jul;103(7):1191-1197. doi: 10.3324/haematol.2017.186577. Epub 2018 Mar 29. |
| 35320921 | Background | Garcia-Sancho AM, Bellei M, Lopez-Parra M, Gritti G, Cortes M, Novelli S, Panizo C, Petrucci L, Gutierrez A, Dlouhy I, Bastos-Oreiro M, Sancho JM, Ramirez MJ, Moraleda JM, Carrillo E, Jimenez-Ubieto AI, Jarque I, Orsucci L, Garcia-Torres E, Montalban C, Dodero A, Arranz R, De Las Heras N, Pascual MJ, Lopez-Jimenez J, Spina M, Re A, De Villambrosia SG, Bobillo S, Federico M, Caballero D. Autologous stem-cell transplantation as consolidation of first-line chemotherapy in patients with peripheral T-cell lymphoma: a multicenter GELTAMO/FIL study. Haematologica. 2022 Nov 1;107(11):2675-2684. doi: 10.3324/haematol.2021.279426. |
| 38532575 | Background | Civallero M, Schroers-Martin JG, Horwitz S, Manni M, Stepanishyna Y, Cabrera ME, Vose J, Spina M, Hitz F, Nagler A, Montoto S, Chiattone C, Skrypets T, Perez Saenz MA, Priolo G, Luminari S, Lymboussaki A, Pavlovsky A, Marino D, Liberati M, Trotman J, Mannina D, Federico M, Advani R. Long-term outcome of peripheral T-cell lymphomas: Ten-year follow-up of the International Prospective T-cell Project. Br J Haematol. 2024 Jul;205(1):166-174. doi: 10.1111/bjh.19433. Epub 2024 Mar 26. |
| 29253087 | Background | Fossard G, Broussais F, Coelho I, Bailly S, Nicolas-Virelizier E, Toussaint E, Lancesseur C, Le Bras F, Willems E, Tchernonog E, Chalopin T, Delarue R, Gressin R, Chauchet A, Gyan E, Cartron G, Bonnet C, Haioun C, Damaj G, Gaulard P, Fornecker L, Ghesquieres H, Tournilhac O, da Silva MG, Bouabdallah R, Salles G, Bachy E. Role of up-front autologous stem-cell transplantation in peripheral T-cell lymphoma for patients in response after induction: an analysis of patients from LYSA centers. Ann Oncol. 2018 Mar 1;29(3):715-723. doi: 10.1093/annonc/mdx787. |
| 31807859 | Background | Ahn SY, Jung SY, Jung SH, Ahn JS, Lee JJ, Kim HJ, Kang SR, Han YH, Kwak JY, Yhim HY, Yang DH. Prognostic significance of FDG-PET/CT in determining upfront autologous stem cell transplantation for the treatment of peripheral T cell lymphomas. Ann Hematol. 2020 Jan;99(1):83-91. doi: 10.1007/s00277-019-03867-9. Epub 2019 Dec 6. |
| 33512419 | Background | Schmitz N, Truemper L, Bouabdallah K, Ziepert M, Leclerc M, Cartron G, Jaccard A, Reimer P, Wagner E, Wilhelm M, Sanhes L, Lamy T, de Leval L, Rosenwald A, Roussel M, Kroschinsky F, Lindemann W, Dreger P, Viardot A, Milpied N, Gisselbrecht C, Wulf G, Gyan E, Gaulard P, Bay JO, Glass B, Poeschel V, Damaj G, Sibon D, Delmer A, Bilger K, Banos A, Haenel M, Dreyling M, Metzner B, Keller U, Braulke F, Friedrichs B, Nickelsen M, Altmann B, Tournilhac O. A randomized phase 3 trial of autologous vs allogeneic transplantation as part of first-line therapy in poor-risk peripheral T-NHL. Blood. 2021 May 13;137(19):2646-2656. doi: 10.1182/blood.2020008825. |
| 25392158 | Background | Loirat M, Chevallier P, Leux C, Moreau A, Bossard C, Guillaume T, Gastinne T, Delaunay J, Blin N, Mahe B, Dubruille V, Augeul-Meunier K, Peterlin P, Maisonneuve H, Moreau P, Juge-Morineau N, Jardel H, Mohty M, Moreau P, Le Gouill S. Upfront allogeneic stem-cell transplantation for patients with nonlocalized untreated peripheral T-cell lymphoma: an intention-to-treat analysis from a single center. Ann Oncol. 2015 Feb;26(2):386-92. doi: 10.1093/annonc/mdu515. Epub 2014 Nov 12. |
| 29549411 | Background | Rohlfing S, Dietrich S, Witzens-Harig M, Hegenbart U, Schonland S, Luft T, Ho AD, Dreger P. The impact of stem cell transplantation on the natural course of peripheral T-cell lymphoma: a real-world experience. Ann Hematol. 2018 Jul;97(7):1241-1250. doi: 10.1007/s00277-018-3288-7. Epub 2018 Mar 16. |
| D009369 |
| Neoplasms |
| D008232 | Lymphoproliferative Disorders |
| D008206 | Lymphatic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
| D007160 | Immunoproliferative Disorders |
| D007154 | Immune System Diseases |
| D001388 |
| Aziridines |
| D001389 | Azirines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D002072 | Butylene Glycols |
| D006018 | Glycols |
| D000438 | Alcohols |
| D008698 | Mesylates |
| D000476 | Alkanesulfonates |
| D017738 | Alkanesulfonic Acids |
| D000473 | Alkanes |
| D006839 | Hydrocarbons, Acyclic |
| D006838 | Hydrocarbons |
| D013451 | Sulfonic Acids |
| D013456 | Sulfur Acids |
| D013457 | Sulfur Compounds |
| D003562 | Cytidine |
| D011741 | Pyrimidine Nucleosides |
| D011743 | Pyrimidines |
| D001087 | Arabinonucleosides |
| D009705 | Nucleosides |
| D009706 | Nucleic Acids, Nucleotides, and Nucleosides |