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

Primary Purpose

Aplastic Anemia

Status
Recruiting
Phase
Phase 2
Locations
China
Study Type
Interventional
Intervention
CD20 monoclonal antibody
ATG
Sponsored by
The First Affiliated Hospital of Soochow University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Aplastic Anemia

Eligibility Criteria

undefined - 50 Years (Child, Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • The First Affiliated Hospital of Soochow UniversityRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Experimental

Arm Label

ATG arm (control group)

ATG + CD20 monoclonal antibody (test arm)

Arm Description

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）

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

Outcomes

Primary Outcome Measures

GVHD incidence
GVHD incidence, location and grade. Infection incidence and recurrence rate.

Secondary Outcome Measures

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

Full Information

First Posted
August 8, 2022
Last Updated
August 21, 2022
Sponsor
The First Affiliated Hospital of Soochow University
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1. Study Identification

Unique Protocol Identification Number
NCT05510505
Brief Title
GVHD Prophylaxis by Addition of CD20 Monoclonal Antibody to the Conditioning Regimen in SAA With Treatment of Allo-HSCT
Official Title
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
Study Type
Interventional

2. Study Status

Record Verification Date
August 2022
Overall Recruitment Status
Recruiting
Study Start Date
December 30, 2021 (Actual)
Primary Completion Date
September 2023 (Anticipated)
Study Completion Date
December 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
The First Affiliated Hospital of Soochow University

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
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 To conduct pharmacogenomic assay in CD20 arm(treatment arm) before conditioning and monitor plasma concentration of CD20 dynamically（7d、14d、28d、56d、91d）. To monitor levels of B cells in peripheral blood dynamically (+90d、+180d、+270d、+360d、+450d、+540d、+630d、+720d) in all patients. To observe and compare the incidence of PTLD between the two arms. To observe and compare immunoglobulin levels after transplantation in all patients. To evaluate transplant-related mortality. To evaluate the effect on hematopoietic reconstruction.
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. Subject enrollment 36months Transplantation to the end of follow-up 24months Data collection and report writing 3months In total 63months

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Aplastic Anemia

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
100 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
ATG arm (control group)
Arm Type
Active Comparator
Arm Description
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）
Arm Title
ATG + CD20 monoclonal antibody (test arm)
Arm Type
Experimental
Arm Description
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
Intervention Type
Drug
Intervention Name(s)
CD20 monoclonal antibody
Other Intervention Name(s)
allogeneic hematopoietic stem cell transplantation
Intervention Description
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
Intervention Type
Drug
Intervention Name(s)
ATG
Intervention Description
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
Primary Outcome Measure Information:
Title
GVHD incidence
Description
GVHD incidence, location and grade. Infection incidence and recurrence rate.
Time Frame
2 years
Secondary Outcome Measure Information:
Title
Infection incidence
Description
Cumulative incidence of infection post-transplant
Time Frame
2 years
Title
GVHD-free survival rate
Description
defined by the percentage of patients who are alive without evidence of moderate or severe chronic GVHD at 2 year
Time Frame
2 years
Title
transplant related mortality
Description
Defined as the number of days from the date of transplant to the date of death related to transplant
Time Frame
2 years
Title
overall survival rate
Description
OS is defined as the number of days from the date of transplant to the date of death
Time Frame
2 years

10. Eligibility

Sex
All
Maximum Age & Unit of Time
50 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Subjects eligible for inclusion in this study must meet all of the following criteria: 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 ALL patients will undergo allo-HSCT. Subjects aged <50 years old with KPS performance status ≥70 at the same time. 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. 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. ALL subjects show none contraindication for allogeneic hematopoietic stem cell transplantation. Patients enrolled in the rituximab group have no contraindications for the use of rituximab. Patients and their clients are willing to perform hematopoietic stem cell transplantation. Potential donor is accessible. Patients have no anti-HLA antibodies. Exclusion Criteria: 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. 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. Past medical history of severe pulmonary dysfunction. Past medical history of diabetes with a propensity for ketoacidosis. Presence of severe coagulopathy, thrombophlebitis or pulmonary embolism. Presence of decompensated liver insufficiency or active hepatitis. Presence of history of severe autoimmune disease. Past medical history of thyroid dysfunction with currently abnormal thyroid function. Any concomitant malignancies that have not been disease-free for 5 years. Past medical history of hypersensitivity to biological products (including antibiotics). Pregnant or nursing woman. Inherited bone marrow failure.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
depei wu
Phone
67781856
Ext
0512
Email
wudepei@suda.edu.cn
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
depei wu
Organizational Affiliation
The First Affiliated Hospital of Soochow University
Official's Role
Principal Investigator
Facility Information:
Facility Name
The First Affiliated Hospital of Soochow University
City
Suzhou
State/Province
Jiangsu
ZIP/Postal Code
215215
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
depei wu
Phone
67781856
Ext
0512
Email
wudepei@suda.edu.cn

12. IPD Sharing Statement

Plan to Share IPD
No

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

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