Leukemia, Myeloid, Acute Clinical Trial
Official title:
Study of Venetoclax and Reduced-intensity Conditioning Regimen(RIC) for Allogeneic Stem Cell Transplantation(Allo-HSCT) in Elderly Patients With High-risk Myeloid Malignancies
This study is a single center, single arm, prospective, phase II clinical study to evaluate the efficacy and safety of Venatoclax combined with reduced intensity conditioning regimen allo-HSCT in the treatment of high-risk myeloid malignancies in the elderly patients.
Status | Recruiting |
Enrollment | 50 |
Est. completion date | November 1, 2024 |
Est. primary completion date | November 1, 2024 |
Accepts healthy volunteers | No |
Gender | All |
Age group | 55 Years and older |
Eligibility | Inclusion Criteria: 1. = 55 years old; 2. High risk myeloid malignancies: 1)No hematological remission(NR) after induction/re-induction treatment for AML; 2)Morphological remission but with persistent positive minimal resident disease(MRD) (Flow cytometry>0.01% and/or fusion gene positive and/or digital polymerase chain reaction(PCR) positive); 3)High risk acute myeloid leukemia(AML) according to 2022 European Leukemia Net(ELN) risk stratification; 4)High risk myelodysplastic syndrome(MDS): IPSS-R score = middle risk-2; therapy-related MDS; MDS with mutation of ASXL1, EZH2, RUNX1, SRSF2, U2AF1, STAG2, NRAS, ZRSR2, or TP53; 5)High risk chronic myelomonocytic leukemia(CMML), MDS/MPN. 3. Patients must have appropriate donor: 1)Related donor must be HLA-A, - B, - C, - DQB1 and - DRB1 matched at least 5/10; 2)Unrelated donor must be HLA-A, - B, - C, - DQB1 and - DRB1 matched at least 8/10; 4. Hematopoietic cell transplantation-comorbidity Index(HCT-CI) score = 4? 5. Eastern Cooperative Oncology Group(ECOG) score 0-2? 6. Liver, kidney and cardiopulmonary functions meet the following requirements: 1. Creatinine=1.5×ULN; 2. Left ventricular ejection fraction >50%; 3. Baseline oxygen saturation>92%; 4. Total bilirubin=1.5×ULN;ALT and AST=2.0×ULN; 5. DLCO= 40% and FEV1 = 50%? 7. Able to understand and sign the Informed Consent Document. Exclusion Criteria: 1. Patients with Venetoclax ineffectiveness; 2. Malignant tumors other than acute myeloid leukemia within 5 years prior to screening, in addition to adequately treated cervical carcinoma in situ, basal cell or squamous cell skin cancer, localized prostate cancer after radical resection, and ductal carcinoma in situ after radical resection; 3. ECOG socre>2; 4. HCT-CI score> 4? 5. Any instability of systemic disease, including but not limited to unstable angina, cerebrovascular accident, or transient cerebral ischemic (within 3 months prior to screening), myocardial infarction (within 3 months prior to screening), congestive heart failure (New York heart association (NYHA) classification = III), need drug therapy of severe arrhythmia, liver, kidney, or metabolic disease; patients with pulmonary hypertension 6. Uncontrolled infection during screening period; Hemodynamic instability associated with infection,a new infection or aggravation of the original infection;new lesions on imaging;fever of unknown cause; 7. Patients with symptoms of central nervous system;greater than grade 2 requiring treatment,paralysis,aphasia,acute cerebral infarction,severe traumatic brain injury,schizophrenia; 8. HIV infection; 9. Patients with active hepatitis B virus (HBV) and active hepatitis C virus (HCV) need antiviral treatment; Patients at risk of HBV activation refer to patients with positive HBsAg or HBeAb but not receiving anti-HBV treatment; 10. History of autoimmune disease; 11. Pregnant or lactating women; 12. Fertile men and women who are unwilling to use contraceptive technology during the treatment period and within 12 months after treatment. |
Country | Name | City | State |
---|---|---|---|
China | Shanghai General Hospital | Shanghai | Shanghai |
Lead Sponsor | Collaborator |
---|---|
Xianmin Song, MD |
China,
Garcia JS, Kim HT, Murdock HM, Cutler CS, Brock J, Gooptu M, Ho VT, Koreth J, Nikiforow S, Romee R, Shapiro R, Loschi F, Ryan J, Fell G, Karp HQ, Lucas F, Kim AS, Potter D, Mashaka T, Stone RM, DeAngelo DJ, Letai A, Lindsley RC, Soiffer RJ, Antin JH. Adding venetoclax to fludarabine/busulfan RIC transplant for high-risk MDS and AML is feasible, safe, and active. Blood Adv. 2021 Dec 28;5(24):5536-5545. doi: 10.1182/bloodadvances.2021005566. — View Citation
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | PFS | Progression free survival for all patients enrolled | 1- year PFS | |
Primary | PFS | Progression free survival for all patients enrolled | 2- year PFS | |
Secondary | OS | Overall survival for all patients enrolled | 1- year OS | |
Secondary | OS | Overall survival for all patients enrolled | 2- year OS | |
Secondary | aGVHD rate | The incidence rate of acute GVHD after transplantation | 180 days after transplantation | |
Secondary | cGVHD rate | The incidence rate of chronic GVHD after transplantation | 1 year after transplantation | |
Secondary | cGVHD rate | The incidence rate of chronic GVHD after transplantation | 2 years after transplantation | |
Secondary | Relapse rate | Cumulative relapse rate after transplantation | 1 year after transplantation | |
Secondary | NRM | Non relapse mortality after transplantation | 2 years after transplantation | |
Secondary | GVHD-free relapse-free survival(GRFS) | Time from transplantation to the diagnosis of chronic GVHD or relapse | 2 years after transplantation | |
Secondary | Reactivation rate of EBV and CMV | Reactivation rate of Epstein-Barr virus and cytomegalovirus after transplantation | 1 year after transplantation | |
Secondary | Reactivation rate of EBV and CMV | Reactivation rate of Epstein-Barr virus and cytomegalovirus after transplantation | 2 years after transplantation |
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