GVHD Prophylaxis by Addition of CD20 Monoclonal Antibody to the Conditioning Regimen in SAA With Treatment of Allo-HSCT
Study Details
Study Description
Brief Summary
Objectives 2.1 Primary objectives
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To observe and compare incidence and severity of aGVHD and cGVHD between the two arms within 2 years after transplantation.
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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
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To conduct pharmacogenomic assay in CD20 arm(treatment arm) before conditioning and monitor plasma concentration of CD20 dynamically(7d、14d、28d、56d、91d).
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To monitor levels of B cells in peripheral blood dynamically (+90d、+180d、+270d、+360d、+450d、+540d、+630d、+720d) in all patients.
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To observe and compare the incidence of PTLD between the two arms.
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To observe and compare immunoglobulin levels after transplantation in all patients.
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To evaluate transplant-related mortality.
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To evaluate the effect on hematopoietic reconstruction.
Condition or Disease | Intervention/Treatment | Phase |
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Phase 2 |
Detailed Description
- 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.
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Subject enrollment 36months
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Transplantation to the end of follow-up 24months
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Data collection and report writing 3months In total 63months
Study Design
Arms and Interventions
Arm | Intervention/Treatment |
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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
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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:
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Outcome Measures
Primary Outcome Measures
- GVHD incidence [2 years]
GVHD incidence, location and grade. Infection incidence and recurrence rate.
Secondary Outcome Measures
- Infection incidence [2 years]
Cumulative incidence of infection post-transplant
- GVHD-free survival rate [2 years]
defined by the percentage of patients who are alive without evidence of moderate or severe chronic GVHD at 2 year
- transplant related mortality [2 years]
Defined as the number of days from the date of transplant to the date of death related to transplant
- overall survival rate [2 years]
OS is defined as the number of days from the date of transplant to the date of death
Eligibility Criteria
Criteria
Inclusion Criteria:
- Subjects eligible for inclusion in this study must meet all of the following criteria:
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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 < 0.510E9/L Platelet count < 2010E9/L Absolute reticulocyte count < 20*10E9/L
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ALL patients will undergo allo-HSCT.
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Subjects aged <50 years old with KPS performance status ≥70 at the same time.
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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.
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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.
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ALL subjects show none contraindication for allogeneic hematopoietic stem cell transplantation.
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Patients enrolled in the rituximab group have no contraindications for the use of rituximab.
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Patients and their clients are willing to perform hematopoietic stem cell transplantation.
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Potential donor is accessible.
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Patients have no anti-HLA antibodies.
Exclusion Criteria:
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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.
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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.
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Past medical history of severe pulmonary dysfunction.
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Past medical history of diabetes with a propensity for ketoacidosis.
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Presence of severe coagulopathy, thrombophlebitis or pulmonary embolism.
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Presence of decompensated liver insufficiency or active hepatitis.
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Presence of history of severe autoimmune disease.
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Past medical history of thyroid dysfunction with currently abnormal thyroid function.
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Any concomitant malignancies that have not been disease-free for 5 years.
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Past medical history of hypersensitivity to biological products (including antibiotics).
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Pregnant or nursing woman.
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Inherited bone marrow failure.
Contacts and Locations
Locations
Site | City | State | Country | Postal Code | |
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1 | The First Affiliated Hospital of Soochow University | Suzhou | Jiangsu | China | 215215 |
Sponsors and Collaborators
- The First Affiliated Hospital of Soochow University
Investigators
- Principal Investigator: depei wu, The First Affiliated Hospital of Soochow University
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- SAA-HSCT-2021