Peripheral Blood Allogenic Stem Cell Transplantation Using Non-anti Thymocyte Globulin Regimens in Severe Aplastic Anemia Patients

Phase 2

• Conditions: Severe Aplastic Anemia
• Interventions: Drug: Non ATG Conditioning regimen; Drug: GVHD Prophylaxis; Procedure: Allogenic Stem Cell Transplantation; Drug: ATG conditioning regimen

• Registration Number: NCT03295058
• Lead Sponsor: Assiut University

Brief Summary

Aplastic anemia is a syndrome of bone marrow failure characterized by peripheral pancytopenia and marrow hypoplasia.The theoretical basis for marrow failure includes primary defects in or damage to the stem cell or the marrow microenvironment

Detailed Description

The distinction between acquired and inherited disease may present a clinical challenge, but more than 80% of cases are acquired.

Therapy for aplastic anemia may consist of supportive care only, immunosuppressive therapy, or hematopoietic cell transplantation. Severe and very severe aplastic anemia have a high mortality rate with supportive care alone .

The British Committee for Standards in Haematology recommends treating infection or uncontrolled bleeding before administering immunosuppressive therapy, including in patients scheduled for hematopoietic cell transplantation. The Pediatric Haemato-Oncology Italian Association recommends hematopoietic cell transplantation from a matched sibling donor for severe aplastic anemia, and if a matched donor is not available, options include immunosuppressive therapy or unrelated donor hematopoietic cell transplantation.

Human leukocyte antigen (HLA)-matched sibling-donor hematopoietic cell transplantation is the treatment of choice for a young patient with severe or very severe aplastic anemia , being generally accepted for patients younger than 40 years.

Recent years have seen increasing the use of hematopoietic cells other than bone marrow (BM). These alternative graft sources include peripheral blood progenitor cells and granulocyte colony stimulating factor (G-CSF) bone marrow (G-BM). Several groups have demonstrated that peripheral blood progenitor cell transplantation has faster neutrophil and platelet engraftment compared to BM in patients with hematologic malignancies ; however, most adult studies also report an increase in chronic GVHD (cGVHD) Some adult studies describe improved survival with peripheral blood progenitor cells in adult recipients although survival generally was no different in those with standard-risk disease .

Cyclophosphamide (Cy)/anti-thymocyte globulin (ATG) is considered the standard conditioning regimen for patients with severe aplastic anemia undergoing hematopoietic cell transplantation from a HLA matched sibling donor, The introduction of a fludarabine (F-araA) based reduced intensity conditioning regimen has extended the availability of hematopoietic cell transplantation to patients who are older, heavily transfused and having delayed treatment from the time of diagnosis with HLA matched related/unrelated donors.

The addition of F-araA to the conditioning regimen has been shown to provide additional immunosuppression for engraftment without increasing toxicity in patients undergoing hematopoietic cell transplantation .

Also, conditioning with F-araA and Cy is associated with improved long-term survival compared to a historical cohort receiving Cy/ATG regimen in patients with severe aplastic anemia undergoing hematopoietic cell transplantation .

Adequate post transplantation immunosuppression is important not only for the prevention of GVHD, but also to secure adequate suppression of the host immune system and prevention of graft rejection. The administration of CsA alone or with or without short-course methotrexate or steroid should be considered the standard post transplantation immunosuppression. In addition to possibility of use of other immunosuppressive agents, including the use of mycophenolate mofetil, particularly in patients with renal impairment.

Study Timeline

• Study First Submitted: 2017-09-24
• Study First Submitted QC: 2017-09-24
• Study First Posted: 2017-09-27
• Status Verified: 2018-11
• Last Update Submitted: 2018-11-24
• Last Update Posted: 2018-11-27
• Study Start: 2019-01-01
• Primary Completion: 2019-12-01
• Study Completion: 2020-06

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 50

Inclusion Criteria

• All patients with severe and very severe aplastic anemia for stem cell therapy.

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Exclusion Criteria

1- Contraindication to stem cell transplantation. 2 - Patients associated co-morbidities.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Non ATG regimen	Non ATG Conditioning regimen	the first 50% of patients will receive Fludarabine + cyclophosphamide prior to hematopoietic cell transplantation. GVHD Prophylaxis: Cyclosporine A All the patient will do allogenic stem cell transplantation from peripheral blood
Non ATG regimen	GVHD Prophylaxis	the first 50% of patients will receive Fludarabine + cyclophosphamide prior to hematopoietic cell transplantation. GVHD Prophylaxis: Cyclosporine A All the patient will do allogenic stem cell transplantation from peripheral blood
Non ATG regimen	Allogenic Stem Cell Transplantation	the first 50% of patients will receive Fludarabine + cyclophosphamide prior to hematopoietic cell transplantation. GVHD Prophylaxis: Cyclosporine A All the patient will do allogenic stem cell transplantation from peripheral blood
ATG regimen	GVHD Prophylaxis	the other 50% will receive Cyclophosphamide + ATG prior to hematopoietic cell transplantation. GVHD Prophylaxis: Cyclosporine A All the patient will do allogenic stem cell transplantation from peripheral blood
ATG regimen	Allogenic Stem Cell Transplantation	the other 50% will receive Cyclophosphamide + ATG prior to hematopoietic cell transplantation. GVHD Prophylaxis: Cyclosporine A All the patient will do allogenic stem cell transplantation from peripheral blood
ATG regimen	ATG conditioning regimen	the other 50% will receive Cyclophosphamide + ATG prior to hematopoietic cell transplantation. GVHD Prophylaxis: Cyclosporine A All the patient will do allogenic stem cell transplantation from peripheral blood

Primary Outcome Measures

Name	Time	Method
Overall Survival rate	two years

Secondary Outcome Measures

Name	Time	Method
Progression free survival	two years
Relapse rate	two years
GVHD occurrence (Acute or Chronic), engraftment and transplant related mortality	two years