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

NCT05510505 | Unknown Phase 2

• 1 other identifier: SAA-HSCT-2021
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 1

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

1. 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. 2.To monitor levels of B cells in peripheral blood dynamically (+90d、+180d、+270d、+360d、+450d、+540d、+630d、+720d) in all patients.
3. 3.To observe and compare the incidence of PTLD between the two arms.
4. 4.To observe and compare immunoglobulin levels after transplantation in all patients.
5. 5.To evaluate transplant-related mortality.
6. 6.To evaluate the effect on hematopoietic reconstruction.

Conditions

Aplastic Anemia

Outcome Measures

Primary Outcomes (1)

• GVHD incidence

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

  2 years

Secondary Outcomes (4)

• Infection incidence

  2 years

• GVHD-free survival rate

  2 years

• transplant related mortality

  2 years

• overall survival rate

  2 years

Study Arms (2)

ATG arm (control group)

ACTIVE COMPARATOR

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

ATG + CD20 monoclonal antibody (test arm)

EXPERIMENTAL

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

Interventions

CD20 monoclonal antibody DRUG

4.2 Conditioning Regimen 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） 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 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） 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

Also known as: allogeneic hematopoietic stem cell transplantation

ATG + CD20 monoclonal antibody (test arm)

ATG DRUG

4.2 Conditioning Regimen 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） 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 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） 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

ATG arm (control group)

Eligibility Criteria

• Age: Up to 50 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• The First Affiliated Hospital of Soochow University: lead

Study Sites (1)

The First Affiliated Hospital of Soochow University

Suzhou, Jiangsu, 215215, China

RECRUITING

MeSH Terms

Conditions

Anemia, Aplastic

Interventions

188Re-anti-CD20 monoclonal antibody

Condition Hierarchy (Ancestors)

Anemia; Hematologic Diseases; Hemic and Lymphatic Diseases; Bone Marrow Failure Disorders; Bone Marrow Diseases

Study Officials

• depei wu

  The First Affiliated Hospital of Soochow University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

depei wu

CONTACT

67781856; wudepei@suda.edu.cn

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: August 8, 2022
• First Posted: August 22, 2022
• Study Start: December 30, 2021
• Primary Completion: September 1, 2023
• Study Completion: December 1, 2025
• Last Updated: August 24, 2022

Record last verified: 2022-08

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)