Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
The purpose of this study is to compare the efficacy and safety of venetoclax+decitabine+busulfan+fludarabine (VEN+DAC+Bu2Flu4) regimen with busulfan+fludarabine (Bu2Flu5) regimen in older patients with myeloid malignancies undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT).
Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a potent curative approach for myeloid malignancies, but outcomes post-transplantation of older population were unsatisfactory. The conditioning regimen is an essential factor affecting outcomes post-transplantation. Currently, the optimal conditioning for older patients with myeloid malignancies remains unclear. Myeloablative conditioning (MAC) regimens like busulfan plus cyclophosphamide, and busulfan plus fludarabine (Bu4Flu4-5) have low relapse rates, but high non-relapse mortality (NRM) is observed in older patients with myeloid malignancies. The development of reduced-intensity conditioning (RIC) regimens such as Bu2Flu5 has decreased NRM and enhanced the feasibility of allo-HSCT in older patients with myeloid malignancies, but it appears to have higher relapse rate. Neither conventional MAC nor RIC regimens benefit older patients with myeloid malignancies. In recent years, some studies reported that the introduction of venetoclax (VEN) or decitabine (DAC) to MAC reduced relapse without increasing NRM in younger patients with high-risk myeloid malignancies. However, whether VEN and DAC combined with RIC regimen reduce relapse without increasing NRM, then improve survival in older patients with myeloid malignancies is unclear. Therefore, we conducted a randomized controlled study to compare the efficacy and safety of VEN+DAC+Bu2Flu4 with Bu2Flu5 in older patients with myeloid malignancies undergoing allo-HSCT.
Not provided
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| VEN+DAC+Bu2Flu4 | Experimental | Venetoclax+Decitabine+Busulfan+Fludarabine |
|
| Bu2Flu5 | Active Comparator | Busulfan+Fludarabine |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Venetoclax (VEN) | Drug | Venetoclax (VEN) was administered at 400mg/day on days -10 to -4. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Disease-free survival (DFS) rate | Will calculate time from random assignment until disease progression or relapse or death from any cause | 2 year |
| Measure | Description | Time Frame |
|---|---|---|
| Overall survival (OS) rate | Will calculate time from random assignment until death from any cause. | 2 year |
| Relapse incidence | Will calculate time from random assignment until relapse or disease progression. |
Not provided
Inclusion Criteria:
Exclusion Criteria:
Not provided
Not provided
Not provided
Not provided
| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Qifa Liu | Contact | +86-020-62787883 | liuqifa628@163.com | |
| Qifa Liu | Contact | +86-020-61641611 | liuqifa628@163.com |
| Name | Affiliation | Role |
|---|---|---|
| Qifa Liu | Nanfang Hospital, Southern Medical University | Principal Investigator |
Not provided
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 37335960 | Background | Ling Y, Xuan L, Xu N, Huang F, Fan Z, Guo Z, Xu X, Liu H, Lin R, Yu S, Zhang H, Jin H, Wu M, Liu C, Liang X, Ou R, Zhang Y, Liu X, Qu H, Zhai X, Sun J, Zhao Y, Liu Q. Busulfan Plus Fludarabine Compared With Busulfan Plus Cyclophosphamide for AML Undergoing HLA-Haploidentical Hematopoietic Cell Transplantation: A Multicenter Randomized Phase III Trial. J Clin Oncol. 2023 Oct 10;41(29):4632-4642. doi: 10.1200/JCO.23.00101. Epub 2023 Jun 19. | |
| 26429297 |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Decitabine (DAC) | Drug | Decitabine (DAC) was administered at 20mg/m2/day on days -10 to -8. |
|
| Busulfan (Bu) | Drug | Busulfan (Bu) was administered at 3.2 mg/kg/day on days -5 to -4. |
|
| Fludarabine (Flu) | Drug | Fludarabine (Flu) was administered at 30mg/m2/day on days -5 to -2. |
|
| Fludarabine (Flu) | Drug | Fludarabine (Flu) was administered at 30mg/m2/day on days -6 to -2. |
|
| 2 year |
| Non-relapse mortality (NRM) incidence | Defined as death from any cause not subsequent to relapse or disease progression. | 2 year |
| Background |
| Rambaldi A, Grassi A, Masciulli A, Boschini C, Mico MC, Busca A, Bruno B, Cavattoni I, Santarone S, Raimondi R, Montanari M, Milone G, Chiusolo P, Pastore D, Guidi S, Patriarca F, Risitano AM, Saporiti G, Pini M, Terruzzi E, Arcese W, Marotta G, Carella AM, Nagler A, Russo D, Corradini P, Alessandrino EP, Torelli GF, Scime R, Mordini N, Oldani E, Marfisi RM, Bacigalupo A, Bosi A. Busulfan plus cyclophosphamide versus busulfan plus fludarabine as a preparative regimen for allogeneic haemopoietic stem-cell transplantation in patients with acute myeloid leukaemia: an open-label, multicentre, randomised, phase 3 trial. Lancet Oncol. 2015 Nov;16(15):1525-1536. doi: 10.1016/S1470-2045(15)00200-4. Epub 2015 Sep 28. |
| 26527780 | Background | Devine SM, Owzar K, Blum W, Mulkey F, Stone RM, Hsu JW, Champlin RE, Chen YB, Vij R, Slack J, Soiffer RJ, Larson RA, Shea TC, Hars V, Sibley AB, Giralt S, Carter S, Horowitz MM, Linker C, Alyea EP. Phase II Study of Allogeneic Transplantation for Older Patients With Acute Myeloid Leukemia in First Complete Remission Using a Reduced-Intensity Conditioning Regimen: Results From Cancer and Leukemia Group B 100103 (Alliance for Clinical Trials in Oncology)/Blood and Marrow Transplant Clinical Trial Network 0502. J Clin Oncol. 2015 Dec 10;33(35):4167-75. doi: 10.1200/JCO.2015.62.7273. Epub 2015 Nov 2. |
| 36702138 | Background | Xuan L, Dai M, Jiang E, Wang Y, Huang F, Fan Z, Xu N, Nie D, Liang X, Chen H, Ye J, Shi P, Liu H, Jin H, Lin R, Yan C, Zhang Y, Sun J, Han M, Liu Q. The effect of granulocyte-colony stimulating factor, decitabine, and busulfan-cyclophosphamide versus busulfan-cyclophosphamide conditioning on relapse in patients with myelodysplastic syndrome or secondary acute myeloid leukaemia evolving from myelodysplastic syndrome undergoing allogeneic haematopoietic stem-cell transplantation: an open-label, multicentre, randomised, phase 3 trial. Lancet Haematol. 2023 Mar;10(3):e178-e190. doi: 10.1016/S2352-3026(22)00375-1. Epub 2023 Jan 23. |
| 37878011 | Background | Zheng X, Gao H, Lu N, Wang M, Zhang H, Zheng Y, Shen B, Cao Y, Chen X, Zhai W, Wei J, Yang D, Zhang R, Pang A, Feng S, Jiang E, Han M. Efficacy of venetoclax combined with decitabine conditioning regimen for allogeneic hematopoietic stem cell transplantation in high-risk and elderly patients with myeloid neoplasms. Ann Hematol. 2023 Dec;102(12):3603-3611. doi: 10.1007/s00277-023-05500-2. Epub 2023 Oct 25. |
| ID | Term |
|---|---|
| C579720 | venetoclax |
| D000077209 | Decitabine |
| D002066 | Busulfan |
| C024352 | fludarabine |
| D007252 | Influenza Vaccines |
| ID | Term |
|---|---|
| D001374 | Azacitidine |
| D001372 | Aza Compounds |
| D009930 | Organic Chemicals |
| D003562 | Cytidine |
| D011741 | Pyrimidine Nucleosides |
| D011743 | Pyrimidines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D009705 | Nucleosides |
| D009706 | Nucleic Acids, Nucleotides, and Nucleosides |
| D012263 | Ribonucleosides |
| 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 |
| D014765 | Viral Vaccines |
| D014612 | Vaccines |
| D001688 | Biological Products |
| D045424 | Complex Mixtures |
Not provided
Not provided