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

NCT ID: NCT03295058

Last Updated: 2018-11-27

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE2/PHASE3
• Total Enrollment: 50 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-01-01
• Study Completion Date: 2020-06-30

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.

Conditions

Severe Aplastic Anemia

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Non ATG 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

Group Type: EXPERIMENTAL

Non ATG Conditioning regimen

Intervention Type: DRUG

50% of the patients will receive Fludarabine + cyclophosphamide (F-araA 120 mg/m2 total dose for 3 days (d-3,-2,-1) over 1 h infusion and cyclophosphamide 25 mg/kg/d (d-5 to d-2) for 4 days over 1-h infusion prior to hematopoietic cell transplantation , then post transplant cyclophosphamide dose 50 mg/kg on days +3 and +4

GVHD Prophylaxis

Intervention Type: DRUG

Cyclosporine A (CsA 3 mg/kg) start day +5

Allogenic Stem Cell Transplantation

Intervention Type: PROCEDURE

using peripheral blood stem cells

ATG 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

Group Type: EXPERIMENTAL

GVHD Prophylaxis

Intervention Type: DRUG

Cyclosporine A (CsA 3 mg/kg) start day +5

Allogenic Stem Cell Transplantation

Intervention Type: PROCEDURE

using peripheral blood stem cells

ATG conditioning regimen

Intervention Type: DRUG

the other 50% of the patients will receive Cyclophosphamide + ATG

Interventions

Non ATG Conditioning regimen

50% of the patients will receive Fludarabine + cyclophosphamide (F-araA 120 mg/m2 total dose for 3 days (d-3,-2,-1) over 1 h infusion and cyclophosphamide 25 mg/kg/d (d-5 to d-2) for 4 days over 1-h infusion prior to hematopoietic cell transplantation , then post transplant cyclophosphamide dose 50 mg/kg on days +3 and +4

Intervention Type: DRUG

GVHD Prophylaxis

Cyclosporine A (CsA 3 mg/kg) start day +5

Intervention Type: DRUG

Allogenic Stem Cell Transplantation

using peripheral blood stem cells

Intervention Type: PROCEDURE

ATG conditioning regimen

the other 50% of the patients will receive Cyclophosphamide + ATG

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

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

Exclusion Criteria

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

• Minimum Eligible Age: 16 Years
• Maximum Eligible Age: 50 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Assiut University

OTHER

Sponsor Role: lead

Responsible Party

Nourhan Taleb Mohamed

Principal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Central Contacts

Osama A Ibraheim, MD

Role: CONTACT

oibrahiem@yahoo.com

00201006372498

Rania M Hafez, MD

Role: CONTACT

raniahafez@ymail.com

00201000019198

References

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Reference Type: BACKGROUND

PMID: 26568159 (View on PubMed)

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Reference Type: BACKGROUND

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Reference Type: BACKGROUND

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Reference Type: BACKGROUND

PMID: 18706160 (View on PubMed)

Couban S, Simpson DR, Barnett MJ, Bredeson C, Hubesch L, Howson-Jan K, Shore TB, Walker IR, Browett P, Messner HA, Panzarella T, Lipton JH; Canadian Bone Marrow Transplant Group. A randomized multicenter comparison of bone marrow and peripheral blood in recipients of matched sibling allogeneic transplants for myeloid malignancies. Blood. 2002 Sep 1;100(5):1525-31. doi: 10.1182/blood-2002-01-0048.

Reference Type: BACKGROUND

PMID: 12176866 (View on PubMed)

Watanabe T, Takaue Y, Kawano Y, Koike K, Kikuta A, Imaizumi M, Watanabe A, Eguchi H, Ohta S, Horikoshi Y, Iwai A, Makimoto A, Kuroda Y; Peripheral Blood Stem Cell Transplantation Study Group of Japan. HLA-identical sibling peripheral blood stem cell transplantation in children and adolescents. Biol Blood Marrow Transplant. 2002;8(1):26-31. doi: 10.1053/bbmt.2002.v8.pm11846353.

Reference Type: BACKGROUND

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Other Identifiers

OPALLSCT

Identifier Type: -

Identifier Source: org_study_id