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
| Name | Class |
|---|---|
| The First Affiliated Hospital of Zhengzhou University | OTHER |
| Peking University People's Hospital | OTHER |
Not provided
Not provided
Not provided
Not provided
This study aims to determine whether the recurrence rate of high-risk acute myeloid leukemia CR1 patients who received allogeneic hematopoietic stem cell transplantation with the Ruxolitinib, Decitabine combined with Bu/Cy or BuF intensive pretreatment regimen is reduced compared with the traditional Bu/Cy or BuFpretreatment regimen.
Allogeneic hematopoietic stem cell transplantation is the only radical treatment for high-risk acute myeloid leukemia (AML), but the traditional Bu/Cy pretreatment regimen is highly toxic and has a high recurrence rate after transplantation (the long-term survival rate is only 10-30%). Although the existing improved regimens such as sequential chemotherapy can reduce the leukemia burden, they lead to prolonged myelosuppression time (17-39 days) and a non-relapse mortality rate as high as 17.2%. There is an urgent need to develop new pretreatment regimens that have both strong anti-leukemia effects and low toxicity.
Studies have found that the JAK-STAT signaling pathway is generally abnormally activated in hematological tumors such as AML. The objective response rate of Ruxolitinib (a JAK1/2 inhibitor) as a monotherapy for relapsed/refractory leukemia reached 45%. When combined with the demethylated drug decitabine, it can synergistically inhibit leukemia cells. Clinical data show that decitabine reduces the recurrence rate after transplantation by 20% (15.0% vs 38.3%), and the combination of the two has good safety. The main adverse reaction is grade 1-2 hematological toxicity.
Our center innovatively proposed the Rux-Dec-mBu/Cy or BuF combined regimen: integrating Ruxolitinib (step-based dose reduction) and decitabine (20mg/m²/d) on the basis of the classic Bu/Cy or BuF. Previous single-arm studies have shown that the one-year recurrence rate of CR1 patients is 0%, and the incidence of toxicity above grade 3 is less than 11%. This study intends to conduct a multicenter randomized controlled trial to verify the superiority of this regimen in reducing recurrence after transplantation in patients with high-risk AML CR1. Its core advantage lies in simultaneously achieving anti-leukemia enhancement (through JAK-STAT targeting and epigenetic regulation) and controllable toxicity (The median grain deficiency time was shortened to 14 days).
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Assigned Interventions | Active Comparator |
|
|
| The control group | No Intervention |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Ruxolitinib, Decitabine | Combination Product |
|
| Measure | Description | Time Frame |
|---|---|---|
| GRFS | GVHD-free, relapse-free survival (GRFS) was defined as a composite endpoint of death from any cause, disease relapse, grade Ⅲ-Ⅳ acute GVHD, or chronic GVHD requiring systemic immunosuppression therapy. | 1 year |
| Measure | Description | Time Frame |
|---|---|---|
| Cumulative recurrence rate (CIR) | Calculated from the first day after stem cell infusion to the last follow-up, the number of patients with hematological or MRD recurrence/the total number of cases ×100%. The definition of hematological recurrence: After remission, patients present with one of the following three conditions: (1) ≥5% of primary lymphocytes and immature lymphocytes in the bone marrow; (2) Extramedullary leukemia occurs; (3) Leukemia cells were found in peripheral blood smears. The definition of MRD recurrence: Leukemia cells are detected by flow cytometry or molecular biology. |
Not provided
Inclusion Criteria:
Exclusion Criteria:
Not provided
Not provided
Not provided
Not provided
| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Li-ping Dou, Dr. | Contact | 86-10-66937079 | lipingruirui@163.com | |
| Dai-hong Liu, Dr. | Contact | 86-10-66937079 | lipingruirui@163.com |
Not provided
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Chinese PLA General Hospital | Recruiting | Beijing | Beijing Municipality | 100853 | China |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 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. | |
| 35371981 |
Not provided
Not provided
Data contain sensitive personal health information
Not provided
Not provided
Not provided
Not provided
Not provided
| ID | Term |
|---|---|
| C540383 | ruxolitinib |
| D000077209 | Decitabine |
| ID | Term |
|---|---|
| D001374 | Azacitidine |
| D001372 | Aza Compounds |
| D009930 | Organic Chemicals |
| D003562 | Cytidine |
Not provided
Not provided
Random Group Assignment
Not provided
Not provided
Not provided
Not provided
| 1 years after transplantation |
| Progression-Free Survival（PFS） | The time from the date of transplantation to the recurrence of leukemia or death for any reason. | 1 years after transplantation |
| CR rate | The proportion of bone marrow in complete remission from the first day after stem cell infusion to +30 days. | 30 days after transplantation |
| The incidence of aGVHD | Calculated from the first day after stem cell infusion, the time from the occurrence of aGVHD, the time of recurrence or death. The actual incidence rate is the number of patients who occur/the total number of cases ×100%. | 100 days after transplantation |
| The incidence of cGVHD | Calculated from the first day after stem cell infusion, the time from the occurrence of cGVHD, the time of recurrence or death. The actual incidence rate is the number of patients who occur/the total number of cases ×100%. | 1 years after transplantation |
| Disease-free survival rate (DFS) | Disease-free survival rate (DFS) refers to the survival period without evidence of recurrence or progression. | 1 years after transplantation |
| Treatment-related safety indicators | Mainly include bacterial infection, viral infection, fungal infection, and PTLD from the time calculated after transplantation to the last follow-up. | 1 years after transplantation |
| Non-relapse mortality | Non-relapse mortality (NRM) was defined as death from any cause other than disease relapse. | 1 year |
| The cumulative incidence of virus reactivation | The cumulative incidence of virus reactivation by Day +180 days post-transplantation was defined as the proportion of virus reactivation occurring at any monitoring point during days 180 post-transplant. | Day +180 days post-transplantation |
| Graft failure | Graft failure was defined as non-engraftment (ie, autologous reconstitution) or graft rejection (ie, secondary loss of donor chimerism) at +28 days | +28 days after transplantation |
| Neutrophil engraftment | Neutrophil engraftment was defined as the first of three consecutive days with a neutrophil count >0.5 ×109/L. | +28 days after transplantation |
| Platelet engraftment | Platelet engraftment was defined as the first of seven consecutive days with a platelet count >20×109/L without transfusion support. | +28 days after transplantation |
| CD4+T cell reconstitution | CD4+T cell reconstitution was defined as CD4+ T cell count ≥ 50/μL in two consecutive measurements within the first 100 days post-transplantation. | the first 100 days post-transplantation |
| Background |
| Li Z, Shi W, Lu X, Lu H, Cao X, Tang L, Yan H, Zhong Z, You Y, Xia L, Hu Y, Wang H. Decitabine-Intensified Modified Busulfan/Cyclophosphamide Conditioning Regimen Improves Survival in Acute Myeloid Leukemia Patients Undergoing Related Donor Hematopoietic Stem Cell Transplantation: A Propensity Score Matched Analysis. Front Oncol. 2022 Mar 16;12:844937. doi: 10.3389/fonc.2022.844937. eCollection 2022. |
| 4908810 | Background | Watanabe T. [Drug tolerance in microorganisms, with special reference to genetic study of its transmission]. Nihon Saikingaku Zasshi. 1969 Oct;24(9):418-25. No abstract available. Japanese. |
| 33637882 | Background | Tang X, Valdez BC, Ma Y, Zhang Q, Qu C, Dai H, Yin J, Li Z, Xu T, Xu Y, Chen J, Zhu X, Chen Z, Wu D, Andersson BS. Low-dose decitabine as part of a modified Bu-Cy conditioning regimen improves survival in AML patients with active disease undergoing allogeneic hematopoietic stem cell transplantation. Bone Marrow Transplant. 2021 Jul;56(7):1674-1682. doi: 10.1038/s41409-021-01238-5. Epub 2021 Feb 26. |
| 7768335 | Background | Tsukada T, Fukushima M, Takebe H, Nakai Y. Vasoactive intestinal peptide gene expression in the rat pheochromocytoma cell line PC12. Mol Cell Endocrinol. 1995 Feb;107(2):231-9. doi: 10.1016/0303-7207(94)03448-3. |
| 16551971 | Background | Schmid C, Schleuning M, Schwerdtfeger R, Hertenstein B, Mischak-Weissinger E, Bunjes D, Harsdorf SV, Scheid C, Holtick U, Greinix H, Keil F, Schneider B, Sandherr M, Bug G, Tischer J, Ledderose G, Hallek M, Hiddemann W, Kolb HJ. Long-term survival in refractory acute myeloid leukemia after sequential treatment with chemotherapy and reduced-intensity conditioning for allogeneic stem cell transplantation. Blood. 2006 Aug 1;108(3):1092-9. doi: 10.1182/blood-2005-10-4165. Epub 2006 Mar 21. |
| 4602511 | Background | Pankhurst R. The earliest history of famine and pestilence in Ethiopia and a note on the "Egyptian Deaths" of 17th and 18th century Ethiopia. Ethiop Med J. 1973 Jul;11(3):233-6. No abstract available. |
| 4126078 | Background | Thomas HC, McSween RN, White RG. Role of the liver in controlling the immunogenicity of commensal bacteria in the gut. Lancet. 1973 Jun 9;1(7815):1288-91. doi: 10.1016/s0140-6736(73)91300-7. No abstract available. |
| 18709502 | Background | Camera A, Rinaldi CR, Palmieri S, Cantore N, Mele G, Mettivier V, Miraglia E, Mastrullo L, Grimaldi F, Luciano L, Guerriero A, Rotoli B, Ferrara F. Sequential continuous infusion of fludarabine and cytarabine associated with liposomal daunorubicin (DaunoXome) (FLAD) in primary refractory or relapsed adult acute myeloid leukemia patients. Ann Hematol. 2009 Feb;88(2):151-8. doi: 10.1007/s00277-008-0571-z. Epub 2008 Aug 16. |
| 24150216 | Background | Fiegl M, Unterhalt M, Kern W, Braess J, Spiekermann K, Staib P, Gruneisen A, Wormann B, Schondube D, Serve H, Reichle A, Hentrich M, Schiel X, Sauerland C, Heinecke A, Rieger C, Beelen D, Berdel WE, Buchner T, Hiddemann W; German AML Cooperative Group (AMLCG). Chemomodulation of sequential high-dose cytarabine by fludarabine in relapsed or refractory acute myeloid leukemia: a randomized trial of the AMLCG. Leukemia. 2014 May;28(5):1001-7. doi: 10.1038/leu.2013.297. Epub 2013 Oct 22. |
| D011741 |
| Pyrimidine Nucleosides |
| D011743 | Pyrimidines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D009705 | Nucleosides |
| D009706 | Nucleic Acids, Nucleotides, and Nucleosides |
| D012263 | Ribonucleosides |