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

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

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.

Study Overview

• Status: Recruiting
• Conditions: Myelodysplastic Syndromes
• Intervention / Treatment: Drug: Venetoclax; Drug: Decetabine; Drug: Azacitidine; Biological: Unrelated Umbilical Cord Blood

• Study Type: Interventional
• Enrollment (Estimated): 14
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Xiaoyu Zhu, MD; Phone Number: 15255456091; Email: xiaoyuz@ustc.edu.cn

Study Locations

• China
  • Anhui
    • Hefei, Anhui, China, 230001
      • Recruiting
      • The First Affiliated Hospital of University of Science and Technology of China
      • Contact: Xiaoyu Zhu, MD; Phone Number: 15255456091; Email: xiaoyuz@ustc.edu.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. 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
2. Patients aged 14-80, gender and race are not limited;
3. Karnofsky score ≥ 60%, Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2;
4. Expected survival time ≥ 3 months;

5. 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%);

6. The recipient and selected donor should be 0-3/10 HLA-matched with same blood type;
7. Patients who voluntarily participate in this clinical study and have signed an informed consent.

Exclusion Criteria:

1. Patients who have suffered from malignant tumors;
2. Patients have suffered from hematopoietic failure after chemotherapy, and have undergone ineffective blood transfusion with unknown cause;
3. Patients who have undergone Class II or above surgery within 4 weeks prior to enrollment;
4. Suffering from life-threatening diseases other than MDS;
5. Allergic to the drugs in the research;
6. 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;
7. Patients with test positive for HIV, HCV or HBV;
8. Stroke or intracranial hemorrhage occurred within 6 months prior to enrollment;
9. Warfarin or vitamin K antagonists (such as phenprocoumarin) is necessary for anticoagulation;
10. Patients with mental illnesses or cognitive impairments;
11. Patients have participated within the month prior to enrollment or patients are currently participating in other clinical trials;
12. There are other conditions that the investigators consider inappropriate for inclusion.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: chemotherapy+Unrelated Umbilical Cord Blood microtransplantation; 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"

Drug: Venetoclax; Patients will be treated with Venetoclax (100 mg on day 1, 200 mg on day 2 and 400 mg on days 3 to 21); Drug: Decetabine; 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); Drug: Azacitidine; 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); Biological: Unrelated Umbilical Cord Blood; The requirements of unrelated umbilical cord blood: recipient-donor HLA match is 0-3/10, same blood type.

What is the study measuring?

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in lymphocyte subsets (NK cells, T cells) before and after treatment	The concentration of lymphocyte subsets in peripheral blood can be detected by flow cytometry	At the time of enrollment and at 1 month
Correlation between human leukocyte antigen (HLA) matching and the concentration of lymphocyte subsets	HLA typing and matching can be assessed by sequence based genotyping (PCR-SBT), and the concentration of lymphocyte subsets in peripheral blood can be detected by flow cytometry	HLA typing and matching will be assessed at the time of enrollment, and the concentration of lymphocyte subsets in peripheral blood will be detected at the time of enrollment and at 1 month

Collaborators and Investigators

• Sponsor: Anhui Provincial Hospital
• Investigators: Principal Investigator: Xiaoyu Zhu, MD, The First Affiliated Hospital of University of Science and Technology of China

Study record dates

Study Major Dates

• Study Start (Estimated): October 27, 2023
• Primary Completion (Estimated): February 1, 2024
• Study Completion (Estimated): February 1, 2026

Study Registration Dates

• First Submitted: October 19, 2023
• First Submitted That Met QC Criteria: October 27, 2023
• First Posted (Actual): October 31, 2023

Study Record Updates

• Last Update Posted (Actual): October 31, 2023
• Last Update Submitted That Met QC Criteria: October 27, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms; Disease; Bone Marrow Diseases; Hematologic Diseases; Precancerous Conditions; Syndrome; Myelodysplastic Syndromes; Preleukemia; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Venetoclax; Azacitidine
• Other Study ID Numbers: UCB-MST&MDS

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No