Combining Venetoclax with Reduced Intensity Conditioning for Elderly Patients with High-risk Myeloid Malignancies

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 testing if a new treatment combining Venetoclax with a gentler chemotherapy can help older patients with serious blood cancers live longer and have fewer complications after a stem cell transplant.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 50 (estimated)
• Ages: 55 Years and up
• Sex: All
• Sponsor: Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine (Academic / other)
• Drugs / interventions: Fludarabine
• Locations: 1 site (Shanghai, Shanghai)
• Trial ID: NCT05583175 on ClinicalTrials.gov

What this trial studies

This clinical trial evaluates the safety and efficacy of Venetoclax in combination with a reduced intensity conditioning regimen for elderly patients suffering from high-risk myeloid malignancies. Participants aged 55 and older will receive a specific treatment regimen involving Venetoclax and other chemotherapy agents, followed by allogeneic hematopoietic stem cell transplantation (allo-HSCT). The study aims to assess progression-free survival and other outcomes such as overall survival and incidence of graft-versus-host disease over a two-year period.

Who should consider this trial

Good fit: Ideal candidates are elderly patients aged 55 and older with high-risk myeloid malignancies who have not achieved remission or have persistent disease.

Not a fit: Patients with low-risk myeloid malignancies or those without an appropriate donor for transplantation may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could improve survival rates and quality of life for elderly patients with high-risk myeloid malignancies.

How similar studies have performed: While there have been studies on Venetoclax for myeloid malignancies, this specific combination with reduced intensity conditioning in elderly patients is relatively novel.

Eligibility criteria

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.

Where this trial is running

Shanghai, Shanghai

• Shanghai General Hospital — Shanghai, Shanghai, China (Recruiting)

Study contacts

• Principal investigator: Xianmin Song — Shanghai General HospitalShanghai General Hospital, Shanghai Jiao Tong University School of Medicine
• Study coordinator: Jie Gao

Conditions Leukemia, Myeloid, Acute; MDS; Hematopoietic Stem Cell Transplantation; Myeloid Malignancy