Safety and Efficacy of Unrelated Umbilical Cord Blood Microtransplantation in Patients With Higher-risk MDS

Study Overview
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Brief Summary
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This study aimed to evaluate the safety and efficacy of unrelated umbilical cord blood microtransplantation in the treatment of above-mentioned MDS patients by observing the factors related to the efficacy and adverse reactions.

Official Title
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A Clinical Study to Evaluate the Safety and Efficacy of Unrelated Umbilical Cord Blood Microtransplantation in Patients With Higher-risk Myelodysplastic Syndromes

Conditions
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Myelodysplastic Syndromes

Intervention / Treatment
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* Biological: Unrelated Umbilical Cord Blood
* Drug: Venetoclax
* Drug: Decetabine
* Drug: Azacitidine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients diagnosed with MDS with WHO criteria through bone marrow morphology, histochemistry, immunophenotyping, pathological testing, etc. Patients can be newly diagnosed, recurrent or unresponsive, with International prognostic scoring system (IPSS-R) score> 3.5 Patients aged 14-80, gender and race are not limited; Karnofsky score ≥ 60%, Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2; Expected survival time ≥ 3 months; The examination results meet the following requirements: ALT and AST ≤ 3 × Upper limit of normal value (ULN); Total bilirubin ≤ 3 × ULN; Creatinine ≤ 2 × ULN or creatinine clearance rate ≥ 40mL/min; The left ventricular ejection fraction (LVEF) measured by echocardiography or multigated acquisition (MUGA) scanning is within the normal range (>50%); The recipient and selected donor should be 0-3/10 HLA-matched with same blood type; Patients who voluntarily participate in this clinical study and have signed an informed consent. Exclusion Criteria: Patients who have suffered from malignant tumors; Patients have suffered from hematopoietic failure after chemotherapy, and have undergone ineffective blood transfusion with unknown cause; Patients who have undergone Class II or above surgery within 4 weeks prior to enrollment; Suffering from life-threatening diseases other than MDS; Allergic to the drugs in the research; Patient with severe cardiac insufficiency, including uncontrolled or symptomatic arrhythmia, congestive heart failure, myocardial infarction within 6 months, or any grade 3 (moderate) or grade 4 (severe) heart disease; Patients with test positive for HIV, HCV or HBV; Stroke or intracranial hemorrhage occurred within 6 months prior to enrollment; Warfarin or vitamin K antagonists (such as phenprocoumarin) is necessary for anticoagulation; Patients with mental illnesses or cognitive impairments; Patients have participated within the month prior to enrollment or patients are currently participating in other clinical trials; There are other conditions that the investigators consider inappropriate for inclusion.

Ages Eligible for Study
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Minimum Age: 14 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: chemotherapy+Unrelated Umbilical Cord Blood microtransplantation<br>Intermittent infusion of HLA mismatched or incompletely matched granulocyte colony-stimulating factor (G-CSF) mobilized peripheral blood stem cells (G-PBSC) during routine chemotherapy without the use of immunosuppressants, abbreviated as microtransplantation | Biological: Unrelated Umbilical Cord Blood<br>* The requirements of unrelated umbilical cord blood: recipient-donor HLA match is 0-3/10, same blood type.<br>Drug: Venetoclax<br>* Patients will be treated with Venetoclax (100 mg on day 1, 200 mg on day 2 and 400 mg on days 3 to 21)<br>Drug: Decetabine<br>* Patients will be treated with Decetabine (20mg/m^2/d on days 1 to 5) or Azacitidine (75mg/m^2/d on days 1 to 7)<br>Drug: Azacitidine<br>* Patients will be treated with Decetabine (20mg/m^2/d on days 1 to 5) or Azacitidine (75mg/m^2/d on days 1 to 7)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Complete response (CR) rate | CR rate is defined as the percentage of patients who met the following conditions: Myelogram: naïve cells less than 5% (at least 200 nucleated cells); Hemogram: absolute neutrophil count > 1.0×10^9/L, platelet count > 100×10^9/L; Clinical diagnosis: no symptoms and signs caused by leukemia infiltration, and patients do not rely on blood transfusion. | 28±7 days | 
| Hematopoietic recovery time | The time of absolute neutrophil count>0.5×10^9/L and platelet count >30×10^9/L for 3 consecutive days. | 28±7 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to Progression（TTP） | Time from enrollment to objective progression of disease | 1 year | 
| Disease Free Survival（DFS） | From CR to recurrence or death or to the date of last follow-up | 1 year | 
| Overall Survival（OS） | From the beginning of treatment to death or to the date of last follow-up | 1 year | 
| Early mortality rate | Death within the first 3 months of induction therapy | 3 months |