GVHD Prophylaxis by Addition of CD20 Monoclonal Antibody to the Conditioning Regimen in SAA With Treatment of Allo-HSCT

A Prospective, Randomized, Multi-center Study to Assess the Efficacy and Safety of GVHD Prophylaxis by Addition of CD20 Monoclonal Antibody to the Conditioning Regimen in Severe Aplastic Anemia Patients With Treatment of Allogeneic HSCT

Objectives 2.1 Primary objectives

1) To observe and compare incidence and severity of aGVHD and cGVHD between the two arms within 2 years after transplantation.

2) To observe and compare the engraftment rate between the two arms. 3) To observe and compare the incidence of infections between the two arms. 2.2 Secondary objectives

1. To conduct pharmacogenomic assay in CD20 arm(treatment arm) before conditioning and monitor plasma concentration of CD20 dynamically（7d、14d、28d、56d、91d）.
2. To monitor levels of B cells in peripheral blood dynamically (+90d、+180d、+270d、+360d、+450d、+540d、+630d、+720d) in all patients.
3. To observe and compare the incidence of PTLD between the two arms.
4. To observe and compare immunoglobulin levels after transplantation in all patients.
5. To evaluate transplant-related mortality.
6. To evaluate the effect on hematopoietic reconstruction.

Study Overview

• Status: Recruiting
• Conditions: Aplastic Anemia
• Intervention / Treatment: Drug: ATG; Drug: CD20 monoclonal antibody

Detailed Description

3. Study design 3.1 Principle of design: prospective, randomized, control, open label 3.2 Subjects: patients with SAA undergoing allogeneic HSCT 3.3 Grouping: In this study, central randomization was used for random enrolment (1:1). After signing the informed consent, patients were randomized into rituximab conditioning group (test group) or non- rituximab conditioning group (control group). Treatment was assigned on a randomized basis according to a 1:1 ratio. The test group and the control group each will include 100 cases.

3.4 Study schedule: This clinical research is to be completed from September 2020 to September 2023.

1. Subject enrollment 36months
2. Transplantation to the end of follow-up 24months
3. Data collection and report writing 3months In total 63months

• Study Type: Interventional
• Enrollment (Anticipated): 100
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: depei wu; Phone Number: 0512 67781856; Email: wudepei@suda.edu.cn

Study Locations

• China
  • Jiangsu
    • Suzhou, Jiangsu, China, 215215
      • Recruiting
      • The First Affiliated Hospital of Soochow University
      • Contact: depei wu; Phone Number: 0512 67781856; Email: wudepei@suda.edu.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 50 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Subjects eligible for inclusion in this study must meet all of the following criteria:

  1. SAA characterized Bone marrow cellularity< 25%, or 25-50% with <30% residual hematopoietic cells and pancytopenia, with at least two of the following parameters in peripheral blood Absolute neutrophil count < 0.5*10E9/L Platelet count < 20*10E9/L Absolute reticulocyte count < 20*10E9/L
  2. ALL patients will undergo allo-HSCT.
  3. Subjects aged <50 years old with KPS performance status ≥70 at the same time.
  4. Aspartate aminotransferase (AST) , alanine aminotransferase (ALT) and alkaline phosphatase≤2 times the upper limit of normal (ULN). Blood urea nitrogen and Creatinine ≤1.25 times ULN.
  5. Cardiac function of subjects must meet all of the following requirements: ECG examination do not reveal any acute myocardial infarction, arrhythmia, or first-degree or higher atrioventricular block. No signs of heart failure. No carrying of active rheumatoid heart disease. Chest radiograph or physical examination do not indicate an enlarged heart.
  6. ALL subjects show none contraindication for allogeneic hematopoietic stem cell transplantation.
  7. Patients enrolled in the rituximab group have no contraindications for the use of rituximab.
  8. Patients and their clients are willing to perform hematopoietic stem cell transplantation.
  9. Potential donor is accessible.
  10. Patients have no anti-HLA antibodies.

Exclusion Criteria:

1. Subject who is unable comprehend or is unwilling to sign an informed consent form or consent form due to severe physical or mental illness resulting in a survival of less than 2 years.
2. Presence of clinically active uncontrolled significant chronic infections (including bacterial, fungal or viral infection), such as dental caries, otitis media, sinusitis, etc., need to be carried out after effective control.
3. Past medical history of severe pulmonary dysfunction.
4. Past medical history of diabetes with a propensity for ketoacidosis.
5. Presence of severe coagulopathy, thrombophlebitis or pulmonary embolism.
6. Presence of decompensated liver insufficiency or active hepatitis.
7. Presence of history of severe autoimmune disease.
8. Past medical history of thyroid dysfunction with currently abnormal thyroid function.
9. Any concomitant malignancies that have not been disease-free for 5 years.
10. Past medical history of hypersensitivity to biological products (including antibiotics).
11. Pregnant or nursing woman.
12. Inherited bone marrow failure.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: ATG arm (control group); 4.2.1 Matched sibling donor 1) ATG arm (control group) Fludarabine 30mg/m2/d×6d（-7d ~ -2d）+ Cyclophosphamide 50mg/kg/d×2d （-4d ~ -3d）+ ATG 2.5mg/kg/d×5d（-8d ~ -4d） 4.2.2 Unrelated donor and haploidentical donor 1) ATG arm (control group) Busulfan 3.2 mg/kg/d（0.8 mg/kg，q6h）×2d（-7d ~ -6d） + Cyclophosphamide 50mg/kg/d×4d （-5d ~ -2d）+ ATG 2.5mg/kg/d×4d（-5d ~ -2d）	Drug: ATG; 4.2 Conditioning Regimen 4.2.1 Matched sibling donor; ATG arm (control group) Fludarabine 30mg/m2/d×6d（-7d ~ -2d）+ Cyclophosphamide 50mg/kg/d×2d （-4d ~ -3d）+ ATG 2.5mg/kg/d×5d（-8d ~ -4d）; ATG + CD20 monoclonal antibody (test arm) Fludarabine 30mg/m2/d×6d（-7d ~ -2d） + Cyclophosphamide 50mg/kg/d×2d （-4d ~ -3d）+ ATG 2.5mg/kg/d×5d（-8d ~ -4d）+ CD20 monoclonal antibody 375mg/m2, -1d 4.2.2 Unrelated donor and haploidentical donor; ATG arm (control group) Busulfan 3.2 mg/kg/d（0.8 mg/kg，q6h）×2d（-7d ~ -6d） + Cyclophosphamide 50mg/kg/d×4d （-5d ~ -2d）+ ATG 2.5mg/kg/d×4d（-5d ~ -2d）; ATG + CD20 monoclonal antibody (test arm) Busulfan 3.2 mg/kg/d（0.8 mg/kg，q6h）×2d（-7d ~ -6d） + Cyclophosphamide 50mg/kg/d×4d （-5d ~ -2d）+ ATG 2.5mg/kg/d×4d（-5d ~ -2d）+ CD20 monoclonal antibody 375mg/m2, -1d
Experimental: ATG + CD20 monoclonal antibody (test arm); 4.2.1 Matched sibling donor 2) ATG + CD20 monoclonal antibody (test arm) Fludarabine 30mg/m2/d×6d（-7d ~ -2d） + Cyclophosphamide 50mg/kg/d×2d （-4d ~ -3d）+ ATG 2.5mg/kg/d×5d（-8d ~ -4d）+ CD20 monoclonal antibody 375mg/m2, -1d 4.2.2 Unrelated donor and haploidentical donor 2) ATG + CD20 monoclonal antibody (test arm) Busulfan 3.2 mg/kg/d（0.8 mg/kg，q6h）×2d（-7d ~ -6d） + Cyclophosphamide 50mg/kg/d×4d （-5d ~ -2d）+ ATG 2.5mg/kg/d×4d（-5d ~ -2d）+ CD20 monoclonal antibody 375mg/m2, -1d	Drug: CD20 monoclonal antibody; 4.2 Conditioning Regimen 4.2.1 Matched sibling donor; ATG arm (control group) Fludarabine 30mg/m2/d×6d（-7d ~ -2d）+ Cyclophosphamide 50mg/kg/d×2d （-4d ~ -3d）+ ATG 2.5mg/kg/d×5d（-8d ~ -4d）; ATG + CD20 monoclonal antibody (test arm) Fludarabine 30mg/m2/d×6d（-7d ~ -2d） + Cyclophosphamide 50mg/kg/d×2d （-4d ~ -3d）+ ATG 2.5mg/kg/d×5d（-8d ~ -4d）+ CD20 monoclonal antibody 375mg/m2, -1d 4.2.2 Unrelated donor and haploidentical donor; ATG arm (control group) Busulfan 3.2 mg/kg/d（0.8 mg/kg，q6h）×2d（-7d ~ -6d） + Cyclophosphamide 50mg/kg/d×4d （-5d ~ -2d）+ ATG 2.5mg/kg/d×4d（-5d ~ -2d）; ATG + CD20 monoclonal antibody (test arm) Busulfan 3.2 mg/kg/d（0.8 mg/kg，q6h）×2d（-7d ~ -6d） + Cyclophosphamide 50mg/kg/d×4d （-5d ~ -2d）+ ATG 2.5mg/kg/d×4d（-5d ~ -2d）+ CD20 monoclonal antibody 375mg/m2, -1d; Other Names: allogeneic hematopoietic stem cell transplantation

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
GVHD incidence	GVHD incidence, location and grade. Infection incidence and recurrence rate.	2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Infection incidence	Cumulative incidence of infection post-transplant	2 years
GVHD-free survival rate	defined by the percentage of patients who are alive without evidence of moderate or severe chronic GVHD at 2 year	2 years
transplant related mortality	Defined as the number of days from the date of transplant to the date of death related to transplant	2 years
overall survival rate	OS is defined as the number of days from the date of transplant to the date of death	2 years

Collaborators and Investigators

• Sponsor: The First Affiliated Hospital of Soochow University
• Investigators: Principal Investigator: Depei Wu, The First Affiliated Hospital of Soochow University

Study record dates

Study Major Dates

• Study Start (Actual): December 30, 2021
• Primary Completion (Anticipated): September 1, 2023
• Study Completion (Anticipated): December 1, 2025

Study Registration Dates

• First Submitted: August 8, 2022
• First Submitted That Met QC Criteria: August 18, 2022
• First Posted (Actual): August 22, 2022

Study Record Updates

• Last Update Posted (Actual): August 24, 2022
• Last Update Submitted That Met QC Criteria: August 21, 2022
• Last Verified: August 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Bone Marrow Diseases; Hematologic Diseases; Bone Marrow Failure Disorders; Anemia; Anemia, Aplastic; Physiological Effects of Drugs; Immunologic Factors; Antibodies; Antibodies, Monoclonal
• Other Study ID Numbers: SAA-HSCT-2021

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