Clinical Study of UCB Combined With UC-MSCs in the Treatment of Bone Marrow Failure Disorders

A Multicenter Collaborative Clinical Study of Umbilical Cord Blood Combined With Umbilical Cord Derived Mesenchymal Stem Cells in the Treatment of Bone Marrow Failure Disorders

The multicenter collaborative clinical study conducted a systematic clinical observation in the treatment of bone marrow failure diseases via UCB&UC-MSCs , in order to observe its clinical efficacy and safety.

Study Overview

• Status: Recruiting
• Conditions: Bone Marrow Failure Disorders
• Intervention / Treatment: Drug: Cyclosporine A; Biological: Umbilical cord blood & Umbilical cord derived mesenchymal stem cells

• Study Type: Interventional
• Enrollment (Estimated): 100
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: zhe Yu, MD; Phone Number: 86-18753103739; Email: doctoryu1120@163.com

Study Locations

• China
  • Shandong
    • Jinan, Shandong, China, 250031
      • Recruiting
      • Shandong Provincial Third Hospital
      • Contact: zhe Yu, MD; Phone Number: 86-18753103739; Email: doctoryu1120@163.com
    • Jinan, Shandong, China
      • Recruiting
      • Affiliated Hospital of Shandong University of Traditional Chinese Medicine
      • Contact: yuan Fang, MD
    • Jining, Shandong, China
      • Recruiting
      • Jining First People's Hospital
      • Contact: haiguo Zhang; Email: wfmchero@126.com
    • Linyi, Shandong, China
      • Recruiting
      • Linyi People's Hospital
      • Contact: yu Xu; Email: xuyumm@qq.com
    • Rizhao, Shandong, China
      • Recruiting
      • Rizhao People's Hospital
      • Contact: Jun Guo
    • Tai'an, Shandong, China
      • Recruiting
      • Tai'an Central Hospital
      • Contact: guanchen Bai
    • Weihai, Shandong, China
      • Recruiting
      • Weihai Municipal Hospital
      • Contact: xiuzhi Deng
    • Yantai, Shandong, China
      • Recruiting
      • Yantai Ludong Hospital (Shandong Provincial Hospital Group)
      • Contact: xiaolei Wang, MD; Email: wxl1978@126.com

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Patients with bone marrow failure disorders, including aplastic anemia, pure red cell aplastic anemia, immune-related pancytopenia, paroxysmal nocturnal hemoglobinuria, myelodysplastic syndrome, acute arrest of hemopoiesis, and cytopenia of unknown significance;
2. Patients with no severe impairment of liver and kidney function (total bilirubin (TBIL): ≤ 1.5×ULN; ALT or AST: ≤ 2.5×ULN; Alkaline phosphatase: ≤ 3×ULN; Serum creatinine: ≤ 1.5×ULN);
3. The prothrombin time (PT) or activated partial thrombin time (APTT) or international normalized ratio (INR): ≤ 1.5×ULN in the absence of anticoagulant therapy;
4. The left ventricular ejection fraction (LVEF): ≥50% by cardiac echocardiography
5. Hepatitis B surface antigen (HBsAg) and Hepatitis B core antibody (HBcAb) were negative. If any of the above items is positive, the HBV DNA titer in peripheral blood must be lower than the detection limit or 1×10^3 copys/ml;
6. Patients with no plans for stem cell transplantation;
7. Patients with ECOG 0-2;
8. Those who voluntarily participate in this clinical study and have signed an informed consent .

Exclusion Criteria:

1. Patients who have suffered malignant tumors other than squamous cell carcinoma of the skin, basal cell carcinoma of the skin, malignant melanoma cured by surgery, and carcinoma in situ of the cervix in the past 5 years;
2. Patient with severe cardiac insufficiency (e.g. grade Ⅲ、Ⅳ by NYHA classification NYHA), and medically uncontrolled hypertension (systolic blood pressure ≥ 160 mmHg or diastolic blood pressure ≥110 mmHg);
3. Patients with severe mental illness;
4. Patients with clinically significant infection should be recruited with delay;
5. AST or ALT: above 3 times the upper limit of normal, creatinine, total bilirubin, or alkaline: phosphatase (ALP): above 1.5 times the upper limit of normal;
6. Patients with test positive for HIV, HCV or syphilis;
7. Patients with severe allergies or allergic to the active ingredients, excipients of the drug, or blood products in this clinical trials;
8. Patients who are pregnant or breastfeeding, or have a childbirth plan in the near future;
9. Patients receive allogeneic/autologous hematopoietic stem cell transplantation by the assessment of investigators;
10. There are other conditions that the investigators consider inappropriate for inclusion.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cyclosporine A	Drug: Cyclosporine A; 3-5 mg per kilogram per day.
Experimental: UCB+UC-MSCs	Biological: Umbilical cord blood & Umbilical cord derived mesenchymal stem cells; Intravenous infusion of umbilical cord blood and umbilical cord derived mesenchymal stem cells (5-8×10^7) at 1 week interval.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective Response Rate (ORR)	To evaluate efficacy of UCB in combination with UC-MSCs in the treatment of bone marrow failure disorders	Up to two years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-free Survival (PFS)	To assess Progression-free Survival (PFS) of the combination	Up to two years
Overall Survival (OS)	To assess overall survival (OS) of the combination	Up to two years

Collaborators and Investigators

• Sponsor: Shandong Qilu Stem Cells Engineering Co., Ltd.
• Collaborators: Second Affiliated Hospital of Zhengzhou University; The Second Affiliated Hospital of Harbin Medical University; The First People's Hospital of Jingzhou; Jiangxi Province Children's Hospital; Shandong Jining No.1 People's Hospital; The Second Affiliated Hospital of Shandong University of traditional Chinese Medicine; Linyi People's Hospital; Weihai Municipal Hospital; Shandong Provincial Third Hospital; Shandong University of Traditional Chinese Medicine; Kaifeng Central Hospital; Dezhou People's Hospital; Binzhou People's Hospital; Zhengzhou Central Hospital; Zigong No.1 Peoples Hospital; Weihai Central Hospital; Rizhao People's Hospital; The Second Affiliated Hospital of Shandong First Medical University; Zibo Municipal Hospital; Shengli Oilfield Central Hospital; Linyi Central Hospital; The affiliated hospital of Jining medical college; Children's Hospital Affiliated to Shandong University; Tai'an Central Hospital; Lanling People's Hospital; The Affiliated Hospital of Binzhou Medical College; Gansu Provincial Hospital of Traditional Chinese Medicine (TCM); Wuwei People's Hospital; Gansu Wuwei Tumour Hospital; Yuncheng Institute of Hematology; Air Force Hospital of Western War Zone; The First People' s Hospital of Yunnan Province; Yantai Ludong Hospital (Shandong Provincial Hospital Group)
• Investigators: Principal Investigator: zhe Yu, MD, Shandong Provincial Third Hospital

Study record dates

Study Major Dates

• Study Start (Actual): August 1, 2023
• Primary Completion (Estimated): April 1, 2025
• Study Completion (Estimated): April 1, 2026

Study Registration Dates

• First Submitted: March 20, 2023
• First Submitted That Met QC Criteria: March 20, 2023
• First Posted (Actual): April 3, 2023

Study Record Updates

• Last Update Posted (Actual): November 29, 2023
• Last Update Submitted That Met QC Criteria: November 26, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Bone Marrow Diseases; Hematologic Diseases; Anemia; Anemia, Hemolytic; Myelodysplastic Syndromes; Anemia, Aplastic; Bone Marrow Failure Disorders; Pancytopenia; Hemoglobinuria, Paroxysmal; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Antirheumatic Agents; Immunosuppressive Agents; Immunologic Factors; Dermatologic Agents; Antifungal Agents; Calcineurin Inhibitors; Cyclosporine; Cyclosporins
• Other Study ID Numbers: UCB&MSCs-BMF-2023

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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