VenentoclaxPhase 3NCT07396480
Fludarabine Plus Melphalan Versus Addition of Venetoclax to Fludarabine/Melphalan Conditioning Regimen for Allogeneic Hematopoietic Stem Cell Transplantation in AML/MDS Patients Aged > 50 Years: a Multicenter, Randomized, Phase 3 Trial
A Phase 3 study testing Venetoclax in combination with fludarabine and melphalan and Fludarabine and Melphalan in people with Venentoclax and Myeloid Malignancies, run by First Affiliated Hospital of Zhejiang University at 18 sites in China.
Trial summary
Allogeneic Hematopoietic Cell Transplantation (Allo-HCT) serves as a curative treatment modality for the vast majority of patients with hematological malignancies. Historically, due to the relatively high treatment-related mortality rate associated with Allo-HCT, this therapy was primarily administered to younger… Read more about this study
- Who is it for?
- Ages 50 to 75 years
- Conditions the study is for
- Venentoclax, Myeloid Malignancies, Conditioning
- What is being tested?
- Venetoclax in combination with fludarabine and melphalan and Fludarabine and Melphalan
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 186 participants
- Where
- 18 sitesChina
- Study dates
- 1 Mar 2026to 30 Jun 2030
- Phase
- Phase 3
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 50 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Aged > 50 years;
- Confirmed as acute myeloid leukemia (AML) in remission prior to transplantation, myelodysplastic syndrome (MDS; IPSS: Intermediate-2, high; or IPSS-R: Intermediate, high, very high; or IPSS-M: moderate-high, high, and very high), or myelodysplastic syndrome/myeloproliferative neoplasm (MDS/MPN) by morphology, immunology, cytogenetics and molecular biology (MICM) typing;
- Having an eligible donor and scheduled to undergo allogeneic hematopoietic stem cell transplantation (Allo-HCT) from a related or unrelated donor;
- Karnofsky Performance Score ≥ 70;
- Eastern Cooperative Oncology Group (ECOG) Performance Status < 3;
- Expected survival time > 12 weeks;
- Voluntarily signing the informed consent form and being able to understand and comply with all study requirements.
Who cannot join
- Complicated with severe cardiac insufficiency with a left ventricular ejection fraction (EF) < 60%; or complicated with severe arrhythmia, and assessed by the investigator as unable to tolerate the intensive conditioning regimen;
- Complicated with severe pulmonary insufficiency (obstructive and/or restrictive ventilatory disorder), and assessed by the investigator as unable to tolerate the intensive conditioning regimen;
- Complicated with severe liver function impairment, with liver function indicators (alanine aminotransferase [ALT], total bilirubin [TBIL]) exceeding 3 times the upper limit of normal (ULN); and assessed by the investigator as unable to tolerate the intensive conditioning regimen;
- Complicated with severe renal insufficiency, with serum creatinine (Cr) exceeding 2 times the upper limit of normal (ULN); or with a 24-hour creatinine clearance rate (Ccr) < 50 ml/min, and assessed by the investigator as unable to tolerate the intensive conditioning regimen;
- Suffering from severe active infection prior to transplantation, and assessed by the investigator as unable to tolerate the intensive conditioning regimen;
- Having a history of allergic reactions or severe adverse reactions to the drugs involved in the conditioning regimen, and assessed by the investigator as ineligible for enrollment;
- Other reasons for ineligibility assessed by the investigator.
Trial locations and contacts
18 sites in 1 country. Contact the study team or a site near you to ask about taking part.
18 sites in 1 country
China18 sites, 18 recruiting
- Recruiting
Xiangya Hospital Central South University
Changsha, Hunan
Yajing Xu, xyyajingxu@csu.edu.cn
- Recruiting
Second Affiliated Hospital of Army Medical University (Xinqiao Hospital)
Chongqing
Xi Zhang, zhangxxi@sina.com
- Recruiting
The First Affiliated Hospital of Fujian Medical University
Fuzhou, Fujian
Ting Yang, 86 13950210357, yang.hopeting@gmail.com
- Recruiting
Nanfang Hospital Southern Medical University
Guangzhou, Guangdong
Li Xuan
- Recruiting
the First Affiliated Hospital, Zhejiang University School of Medicine
Hangzhou, Zhejiang, 311121
Yi Luo, Professor, 0571 87233801, luoyijr@zju.edu.cn
- Recruiting
Zhejiang Cancer Hospital & Hangzhou Institute of Medicine, Chinese Academy of Sciences
Hangzhou, Zhejiang
Yamin Tan, 0571-88122153, yamin0001@126.com
- Recruiting
Sir Run Run Shaw Hospital Zhejiang University School of Medicine
Hangzhou
Haowen Xiao, 0571 86090073, haowenxiaoxiao@126.com
- Recruiting
The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Traditional Chinese Medicine)
Hangzhou
Baodong Ye, 86 13588453501, 13588453501@163.com
- Recruiting
The Second Affiliated Hospital, Zhejiang University School of Medicine
Hangzhou
Yang Xu, 0571 87783777, yxu@zju.edu.cn
- Recruiting
Zhejiang Provincial Peoples's Hospital
Hangzhou
JianPing Lan, 86 13858039689, lanjp@163.com
- Recruiting
Qilu Hospital of Shandong University
Jinan, Shandong
Xinguang Liu
- Recruiting
Jiangsu Province Hospital (The First Affiliated Hospital of Nanjing Medical University)
Nanjing, Jiangsu
Kourong Miao, kourongmiao@163.com
- Recruiting
The Affiliated People's Hospital of Ningbo University
Ningbo
Ying Lu, 0574-87016888, 814871416@qq.com
- Recruiting
The First Affiliated Hospital of Ningbo University
Ningbo
Guifang Ouyang, 0574-87085588, nbougf@163.com
- Recruiting
Shanghai General Hospital (Shanghai First People's Hospital)
Shanghai
Xianmin Song
- Recruiting
The First Affiliated Hospital of Wenzhou Medical University
Wenzhou
Yi Chen, 0577-88069292, chenyi19527@163.com
- Recruiting
Union Hospital, Tongji Medical College, Huazhong University of Science and Technology
Wuhan, Hubei
Linghui Xia
- Recruiting
The First Affiliated Hospital of Zhengzhou University
Zhengzhou, Henan
Weijie Cao, caoweijie2003@126.com
About this study
Allogeneic Hematopoietic Cell Transplantation (Allo-HCT) serves as a curative treatment modality for the vast majority of patients with hematological malignancies. Historically, due to the relatively high treatment-related mortality rate associated with Allo-HCT, this therapy was primarily administered to younger patients. However, the median age at onset of most hematological malignancies falls within the elderly population. For instance, the median ages at onset of Acute Myeloid Leukemia (AML) and Myelodysplastic Syndrome (MDS) are 68 and 77 years, respectively. In recent years, with the advancement of transplantation techniques and the application of Reduced-intensity Conditioning (RIC) regimens, a growing number of elderly patients have undergone Allo-HCT. Data from the Center for International Blood and Marrow Transplant Research (CIBMTR) indicate that in 2017, 31% of patients who received Allo-HCT were aged over 60 years, and 6% were over 70 years old. Over the past decade, the number of elderly patients undergoing Allo-HCT has increased significantly.
Given that most elderly patients cannot tolerate conventional myeloablative conditioning regimens, RIC regimens based on Fludarabine (Flu) combined with Busulfan (Bu), or Fludarabine (Flu) combined with Melphalan (Mel) are currently widely used in elderly patients undergoing Allo-HCT. Nevertheless, the post-transplant relapse rate remains as high as 30%-55%, and the long-term GVHD-free and Relapse-free Survival (GRFS) rate fluctuates between 21% and 59%, suggesting that the efficacy of transplantation needs to be further improved. Further comparison of the commonly used RIC regimens in elderly patients-namely Flu+Bu (2-day), Flu+Bu (4-day) and Flu+Mel-has demonstrated that the Flu+Mel regimen yields superior transplantation outcomes over the Flu+Bu regimens.
Read more
At present, the optimal RIC regimen for elderly patients with hematological malignancies has not yet been clearly defined. The selection of transplantation conditioning regimens for elderly patients should strike a balance between reducing non-relapse mortality and decreasing post-transplant relapse. Over the past 20 years, an increasing number of targeted drugs acting on specific cellular signaling pathways, anti-apoptotic proteins, epigenetic regulators, and monoclonal antibodies have been introduced into clinical practice, thereby revolutionizing the treatment landscape of hematological malignancies. These novel targeted therapies not only bring hope of achieving remission to patients with hematological tumors resistant to traditional chemotherapy, but also the combined application of novel drugs and Allo-HCT is bound to fundamentally transform the overall technical system of hematopoietic stem cell transplantation. Venetoclax is a potent and selective oral inhibitor targeting the BH3 domain of the anti-apoptotic protein Bcl-2. In 2018, the FDA approved Venetoclax as a first-line induction chemotherapy agent for elderly AML patient's ineligible for intensive chemotherapy, with a complete remission rate of up to 67% and favorable tolerability¹¹. Preclinical studies using Allo-HCT animal models have confirmed that the addition of a Bcl-2 inhibitor to RIC regimens can promote donor cell engraftment, reduce the incidence of GVHD, without impairing the graft-versus-leukemia (GVL) effect¹². In recent years, clinical trials have reported the efficacy and safety of the conditioning regimen combining Venetoclax with Flu+Bu in patients with myeloid malignancies undergoing Allo-HCT. Our research center has demonstrated the favorable safety profile and promising long-term survival outcomes of the Venetoclax plus Flu+Mel conditioning regimen in a phase II clinical trial involving patients aged over 50 years with AML/MDS undergoing Allo-HCT (2024 EBMT Poster B093; 2025 EBMT Poster B126). However, the long-term superiority of this novel regimen over the conventional Flu+Mel conditioning regimen remains to be clarified.
Therefore, based on the existing findings from clinical studies and Allo-HCT animal model research, we hypothesize that incorporating Venetoclax into the Fludarabine+Melphalan conditioning regimen for elderly patients undergoing Allo-HCT is expected to improve long-term post-transplant survival and further enhance the transplantation efficacy in this patient population.
Read the detailed description
Patients aged over 50 years diagnosed with acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS) who met the inclusion and exclusion criteria were enrolled in this study. Stratified by age (< 60 years vs. ≥ 60 years) and disease type (AML vs. MDS), the patients were randomly assigned to two groups: the control group, which received the conditioning regimen of fludarabine plus melphalan; and the experimental group, which received the conditioning regimen of venetoclax combined with fludarabine and melphalan.
- Conditioning Regimen for the Experimental Group 1) Venetoclax: 400 mg/day, days -8 to -2. (Note: If fluconazole is co - administered for antifungal prophylaxis during the transplantation conditioning period, the dose of Venetoclax should be reduced to 50% of the standard dose (i.e., 200 mg/day). If voriconazole or posaconazole is used for antifungal prophylaxis, the dose of Venetoclax should be reduced to 25% of the standard dose (i.e., 100 mg/day).) 2) Fludarabine (Flu): 30 mg/m²/day, days -7 to -3. 3) Melphalan (Mel) dose, adjusted according to the patient's age:
- For patients aged < 60 years: 140 mg/m²/day, day -2.
- For patients aged 60 ≤ age < 70 years: 120 mg/m²/day, day -2.
- For patients aged ≥ 70 years: 100 mg/m²/day, day -2.
- Conditioning Regimen for the Control Group 1) Fludarabine (Flu): 30 mg/m²/day, days -7 to -3. 2) Melphalan (Mel) dose, adjusted according to the patient's age:
- For patients aged < 60 years: 140 mg/m²/day, day -2.
- For patients aged 60 ≤ age < 70 years: 120 mg/m²/day, day -2.
- For patients aged ≥ 70 years: 100 mg/m²/day, day -2.
- Conditions
- Venentoclax, Myeloid Malignancies, Conditioning, ALLOGENEIC HEMATOPOIETIC STEM CELL TRANSPLANTATION, Acute Myeloid Leucemia, Myeldysplastic Syndrome (MDS)
- Being tested
- Venetoclax in combination with fludarabine and melphalan, Fludarabine and Melphalan
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Venetoclax in combination with fludarabine and melphalanDrug
VFM Conditioning Regimen:
- Venetoclax: 400 mg/day, days -8 to -2. (Note: If fluconazole is co - administered for antifungal prophylaxis during the transplantation conditioning period, the dose of Venetoclax should be reduced to 50% of the standard dose (i.e., 200 mg/day). If voriconazole or posaconazole is used for antifungal prophylaxis, the dose of Venetoclax should be reduced to 25% of the standard dose (i.e., 100 mg/day).
- Fludarabine (Flu): 30 mg/m²/day, days -7 to -3.
- Melphalan (Mel) dose, adjusted according to the patient's age:
- For patients aged < 60 years: 140 mg/m²/day, day -2.
- For patients aged 60 ≤ age < 70 years: 120 mg/m²/day, day -2.
- For patients aged ≥ 70 years: 100 mg/m²/day, day -2.
Fludarabine and MelphalanDrug
FM conditioning regimen:
- Fludarabine (Flu): 30 mg/m²/day, days -7 to -3.
- Melphalan (Mel) dose, adjusted according to the patient's age:
- For patients aged < 60 years: 140 mg/m²/day, day -2.
- For patients aged 60 ≤ age < 70 years: 120 mg/m²/day, day -2.
- For patients aged ≥ 70 years: 100 mg/m²/day, day -2.
| Study group | Role | What they receive |
|---|---|---|
| FM | Active comparator | Fludarabine and Melphalan Receives: Drug: Fludarabine and Melphalan |
| VFM | Experimental | Venetoclax in combination with fludarabine and melphalan Receives: Drug: Venetoclax in combination with fludarabine and melphalan |
What is being measured
The primary outcome is the main question the study is designed to answer.
GVHD-free and Relapse-free Survival (GRFS)
the time from the date of transplantation to the first occurrence of any of the following events: development of grade Ⅲ-Ⅳ acute graft-versus-host disease (aGVHD); development of moderate to severe chronic graft-versus-host disease (cGVHD); disease relapse or progression; death from any cause.
Measured: 2-year
Secondary outcomes (7)
Overall Survival (OS)
The time from the date of transplantation to death from any cause.
Measured: 2-Year
Progression-free Survival (PFS)
The time from the date of transplantation to disease relapse, progression, or death from any cause.
Measured: 2-Year
Non-relapse Mortality (NRM)
The time from the date of transplantation to death from non-relapse causes, with disease relapse considered as a competing event.
Measured: 2-year
Cumulative Incidence of Relapse (CIR)
Bone marrow blasts/immature cells > 5%, presence of blasts in peripheral blood, or occurrence of extramedullary leukemia; death without relapse is considered as a competing event.
Measured: 2-year
Chronic Graft-versus-host Disease (cGVHD)
Based on the 2014 NIH Diagnostic and Grading Criteria for Chronic GVHD.
Measured: 2-year
Acute Graft-versus-host Disease (aGVHD)
Based on the 2016 Diagnostic and Grading Criteria for Acute GVHD by Harris et al.
Measured: 100-day
Immune Reconstitution (IR)
Recovery status of peripheral blood T, B, NK cell subsets and immunoglobulin levels.
Measured: 2-year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Feb 2026
- Study start1 Mar 2026 (estimated)
- Primary completion31 Jan 2030 (estimated)
- Study completion30 Jun 2030 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for VenentoclaxStudies of the same condition, open and under way.
- More trials run by First Affiliated Hospital of Zhejiang UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- 1. the Experimental Group ① Venetoclax: 400 mg/day, days -8 to -2. (Note: If fluconazole is co - administered for antifungal prophylaxis during the transplantation conditioning period, the dose of Venetoclax should be reduced to 50% of the standard dose (i.e., 200 mg/day). If voriconazole or posaconazole is used for antifungal prophylaxis, the dose of Venetoclax should be reduced to 25% of the standard dose (i.e., 100 mg/day).) ② Fludarabine (Flu): 30 mg/m²/day, days -7 to -3. ③ Melphalan (Mel) dose, adjusted according to the patient's age: 1. For patients aged \< 60 years: 140 mg/m²/day, day -2. 2. For patients aged 60 ≤ age \< 70 years: 120 mg/m²/day, day -2. 3. For patients aged ≥ 70 years: 100 mg/m²/day, day -2. 2. the Control Group ① Fludarabine (Flu): 30 mg/m²/day, days -7 to -3. ② Melphalan (Mel) dose, adjusted according to the patient's age
- Masking
- None (open label)
- Enrolment
- 186 participants (estimated)
Sponsor and investigators
- Lead sponsor
- First Affiliated Hospital of Zhejiang University
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07396480
- Sponsor's protocol ID
- ZJU-HSCT-VFM
- Status last verified
- Jan 2026
- First submitted
- 2 Feb 2026
- Last updated
- 17 Mar 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 17 Mar 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Fludarabine Plus Melphalan Versus Addition of Venetoclax to Fludarabine/Melphalan Conditioning Regimen for Allogeneic Hematopoietic Stem Cell Transplantation in AML/MDS Patients Aged > 50 Years: a Multicenter, Randomized, Phase 3 Trial
- ClinicalTrials.gov ID
- NCT07396480
- Acronym / sponsor ID
- ZJU-HSCT-VFM
- Conditions
- Venentoclax, Myeloid Malignancies, Conditioning, ALLOGENEIC HEMATOPOIETIC STEM CELL TRANSPLANTATION, Acute Myeloid Leucemia, Myeldysplastic Syndrome (MDS)
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 186 participants (estimated)
- Lead sponsor
- First Affiliated Hospital of Zhejiang UniversityUniversity, hospital or other
- Study start
- 1 Mar 2026 (estimated)
- Primary completion
- 31 Jan 2030 (estimated)
- Study completion
- 30 Jun 2030 (estimated)
- First posted
- 9 Feb 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Allogeneic Hematopoietic Cell Transplantation (Allo-HCT) serves as a curative treatment modality for the vast majority of patients with hematological malignancies. Historically, due to the relatively high treatment-related mortality rate associated with Allo-HCT, this therapy was primarily administered to younger patients. However, the median age at onset of most hematological malignancies falls within the elderly population. For instance, the median ages at onset of Acute Myeloid Leukemia (AML) and Myelodysplastic Syndrome (MDS) are 68 and 77 years, respectively. In recent years, with the advancement of transplantation techniques and the application of Reduced-intensity Conditioning (RIC) regimens, a growing number of elderly patients have undergone Allo-HCT. Data from the Center for International Blood and Marrow Transplant Research (CIBMTR) indicate that in 2017, 31% of patients who received Allo-HCT were aged over 60 years, and 6% were over 70 years old. Over the past decade, the number of elderly patients undergoing Allo-HCT has increased significantly.
Given that most elderly patients cannot tolerate conventional myeloablative conditioning regimens, RIC regimens based on Fludarabine (Flu) combined with Busulfan (Bu), or Fludarabine (Flu) combined with Melphalan (Mel) are currently widely used in elderly patients undergoing Allo-HCT. Nevertheless, the post-transplant relapse rate remains as high as 30%-55%, and the long-term GVHD-free and Relapse-free Survival (GRFS) rate fluctuates between 21% and 59%, suggesting that the efficacy of transplantation needs to be further improved. Further comparison of the commonly used RIC regimens in elderly patients-namely Flu+Bu (2-day), Flu+Bu (4-day) and Flu+Mel-has demonstrated that the Flu+Mel regimen yields superior transplantation outcomes over the Flu+Bu regimens.
At present, the optimal RIC regimen for elderly patients with hematological malignancies has not yet been clearly defined. The selection of transplantation conditioning regimens for elderly patients should strike a balance between reducing non-relapse mortality and decreasing post-transplant relapse. Over the past 20 years, an increasing number of targeted drugs acting on specific cellular signaling pathways, anti-apoptotic proteins, epigenetic regulators, and monoclonal antibodies have been introduced into clinical practice, thereby revolutionizing the treatment landscape of hematological malignancies. These novel targeted therapies not only bring hope of achieving remission to patients with hematological tumors resistant to traditional chemotherapy, but also the combined application of novel drugs and Allo-HCT is bound to fundamentally transform the overall technical system of hematopoietic stem cell transplantation. Venetoclax is a potent and selective oral inhibitor targeting the BH3 domain of the anti-apoptotic protein Bcl-2. In 2018, the FDA approved Venetoclax as a first-line induction chemotherapy agent for elderly AML patient's ineligible for intensive chemotherapy, with a complete remission rate of up to 67% and favorable tolerability¹¹. Preclinical studies using Allo-HCT animal models have confirmed that the addition of a Bcl-2 inhibitor to RIC regimens can promote donor cell engraftment, reduce the incidence of GVHD, without impairing the graft-versus-leukemia (GVL) effect¹². In recent years, clinical trials have reported the efficacy and safety of the conditioning regimen combining Venetoclax with Flu+Bu in patients with myeloid malignancies undergoing Allo-HCT. Our research center has demonstrated the favorable safety profile and promising long-term survival outcomes of the Venetoclax plus Flu+Mel conditioning regimen in a phase II clinical trial involving patients aged over 50 years with AML/MDS undergoing Allo-HCT (2024 EBMT Poster B093; 2025 EBMT Poster B126). However, the long-term superiority of this novel regimen over the conventional Flu+Mel conditioning regimen remains to be clarified.
Therefore, based on the existing findings from clinical studies and Allo-HCT animal model research, we hypothesize that incorporating Venetoclax into the Fludarabine+Melphalan conditioning regimen for elderly patients undergoing Allo-HCT is expected to improve long-term post-transplant survival and further enhance the transplantation efficacy in this patient population.
Detailed description
Patients aged over 50 years diagnosed with acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS) who met the inclusion and exclusion criteria were enrolled in this study. Stratified by age (< 60 years vs. ≥ 60 years) and disease type (AML vs. MDS), the patients were randomly assigned to two groups: the control group, which received the conditioning regimen of fludarabine plus melphalan; and the experimental group, which received the conditioning regimen of venetoclax combined with fludarabine and melphalan.
- Conditioning Regimen for the Experimental Group 1) Venetoclax: 400 mg/day, days -8 to -2. (Note: If fluconazole is co - administered for antifungal prophylaxis during the transplantation conditioning period, the dose of Venetoclax should be reduced to 50% of the standard dose (i.e., 200 mg/day). If voriconazole or posaconazole is used for antifungal prophylaxis, the dose of Venetoclax should be reduced to 25% of the standard dose (i.e., 100 mg/day).) 2) Fludarabine (Flu): 30 mg/m²/day, days -7 to -3. 3) Melphalan (Mel) dose, adjusted according to the patient's age:
- For patients aged < 60 years: 140 mg/m²/day, day -2.
- For patients aged 60 ≤ age < 70 years: 120 mg/m²/day, day -2.
- For patients aged ≥ 70 years: 100 mg/m²/day, day -2.
- Conditioning Regimen for the Control Group 1) Fludarabine (Flu): 30 mg/m²/day, days -7 to -3. 2) Melphalan (Mel) dose, adjusted according to the patient's age:
- For patients aged < 60 years: 140 mg/m²/day, day -2.
- For patients aged 60 ≤ age < 70 years: 120 mg/m²/day, day -2.
- For patients aged ≥ 70 years: 100 mg/m²/day, day -2.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- 1. the Experimental Group ① Venetoclax: 400 mg/day, days -8 to -2. (Note: If fluconazole is co - administered for antifungal prophylaxis during the transplantation conditioning period, the dose of Venetoclax should be reduced to 50% of the standard dose (i.e., 200 mg/day). If voriconazole or posaconazole is used for antifungal prophylaxis, the dose of Venetoclax should be reduced to 25% of the standard dose (i.e., 100 mg/day).) ② Fludarabine (Flu): 30 mg/m²/day, days -7 to -3. ③ Melphalan (Mel) dose, adjusted according to the patient's age: 1. For patients aged < 60 years: 140 mg/m²/day, day -2. 2. For patients aged 60 ≤ age < 70 years: 120 mg/m²/day, day -2. 3. For patients aged ≥ 70 years: 100 mg/m²/day, day -2. 2. the Control Group ① Fludarabine (Flu): 30 mg/m²/day, days -7 to -3. ② Melphalan (Mel) dose, adjusted according to the patient's age
| Arm | Type | Receives |
|---|---|---|
| FM | Active comparator | Drug: Fludarabine and MelphalanFludarabine and Melphalan |
| VFM | Experimental | Drug: Venetoclax in combination with fludarabine and melphalanVenetoclax in combination with fludarabine and melphalan |
Who may qualify
- Ages
- 50 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Aged > 50 years;
- Confirmed as acute myeloid leukemia (AML) in remission prior to transplantation, myelodysplastic syndrome (MDS; IPSS: Intermediate-2, high; or IPSS-R: Intermediate, high, very high; or IPSS-M: moderate-high, high, and very high), or myelodysplastic syndrome/myeloproliferative neoplasm (MDS/MPN) by morphology, immunology, cytogenetics and molecular biology (MICM) typing;
- Having an eligible donor and scheduled to undergo allogeneic hematopoietic stem cell transplantation (Allo-HCT) from a related or unrelated donor;
- Karnofsky Performance Score ≥ 70;
- Eastern Cooperative Oncology Group (ECOG) Performance Status < 3;
Key exclusion criteria (7 listed)
- Complicated with severe cardiac insufficiency with a left ventricular ejection fraction (EF) < 60%; or complicated with severe arrhythmia, and assessed by the investigator as unable to tolerate the intensive conditioning regimen;
- Complicated with severe pulmonary insufficiency (obstructive and/or restrictive ventilatory disorder), and assessed by the investigator as unable to tolerate the intensive conditioning regimen;
- Complicated with severe liver function impairment, with liver function indicators (alanine aminotransferase [ALT], total bilirubin [TBIL]) exceeding 3 times the upper limit of normal (ULN); and assessed by the investigator as unable to tolerate the intensive conditioning regimen;
- Complicated with severe renal insufficiency, with serum creatinine (Cr) exceeding 2 times the upper limit of normal (ULN); or with a 24-hour creatinine clearance rate (Ccr) < 50 ml/min, and assessed by the investigator as unable to tolerate the intensive conditioning regimen;
- Suffering from severe active infection prior to transplantation, and assessed by the investigator as unable to tolerate the intensive conditioning regimen;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Venetoclax in combination with fludarabine and melphalanVFM Conditioning Regimen: 1. Venetoclax: 400 mg/day, days -8 to -2. (Note: If fluconazole is co - administered for antifungal prophylaxis during the transplantation conditioning period, the dose of Venetoclax should be reduced to 50% of the standard dose (i.e., 200 mg/day). If voriconazole or posaconazole is used for antifungal prophylaxis, the dose of Venetoclax should be reduced to 25% of the standard dose (i.e., 100 mg/day). 2. Fludarabine (Flu): 30 mg/m²/day, days -7 to -3. 3. Melphalan (Mel) dose, adjusted according to the patient's age: 1. For patients aged < 60 years: 140 mg/m²/day, day -2. 2. For patients aged 60 ≤ age < 70 years: 120 mg/m²/day, day -2. 3. For patients aged ≥ 70 years: 100 mg/m²/day, day -2. | Drug | VFM |
| Fludarabine and MelphalanFM conditioning regimen: 1. Fludarabine (Flu): 30 mg/m²/day, days -7 to -3. 2. Melphalan (Mel) dose, adjusted according to the patient's age: 1. For patients aged < 60 years: 140 mg/m²/day, day -2. 2. For patients aged 60 ≤ age < 70 years: 120 mg/m²/day, day -2. 3. For patients aged ≥ 70 years: 100 mg/m²/day, day -2. | Drug | FM |
Primary outcome
GVHD-free and Relapse-free Survival (GRFS)
Time frame: 2-year
the time from the date of transplantation to the first occurrence of any of the following events: development of grade Ⅲ-Ⅳ acute graft-versus-host disease (aGVHD); development of moderate to severe chronic graft-versus-host disease (cGVHD); disease relapse or progression; death from any cause.
7 secondary outcomes
Overall Survival (OS)
Time frame: 2-Year
Progression-free Survival (PFS)
Time frame: 2-Year
Non-relapse Mortality (NRM)
Time frame: 2-year
Cumulative Incidence of Relapse (CIR)
Time frame: 2-year
Chronic Graft-versus-host Disease (cGVHD)
Time frame: 2-year
Acute Graft-versus-host Disease (aGVHD)
Time frame: 100-day
Immune Reconstitution (IR)
Time frame: 2-year
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Mar 2026.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
18 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Venetoclax in combination with fludarabine and melphalan and Fludarabine and Melphalan in people with Venentoclax and Myeloid Malignancies, run by First Affiliated Hospital of Zhejiang University at 18 sites in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 17 Mar 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 18 sites in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Yi Luo, Professor (0571 87233801, luoyijr@zju.edu.cn), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
GVHD-free and Relapse-free Survival (GRFS) (time frame: 2-year). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Mar 2026.