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

Primary Purpose

Severe Aplastic Anemia

Status
Unknown status
Phase
Phase 2
Locations
Study Type
Interventional
Intervention
Non ATG Conditioning regimen
GVHD Prophylaxis
Allogenic Stem Cell Transplantation
ATG conditioning regimen
Sponsored by
Assiut University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Severe Aplastic Anemia

Eligibility Criteria

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

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.

Sites / Locations

    Arms of the Study

    Arm 1

    Arm 2

    Arm Type

    Experimental

    Experimental

    Arm Label

    Non ATG regimen

    ATG regimen

    Arm Description

    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

    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

    Outcomes

    Primary Outcome Measures

    Overall Survival rate

    Secondary Outcome Measures

    GVHD occurrence (Acute or Chronic), engraftment and transplant related mortality
    Relapse rate
    Progression free survival

    Full Information

    First Posted
    September 24, 2017
    Last Updated
    November 24, 2018
    Sponsor
    Assiut University
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    1. Study Identification

    Unique Protocol Identification Number
    NCT03295058
    Brief Title
    Peripheral Blood Allogenic Stem Cell Transplantation Using Non-anti Thymocyte Globulin Regimens in Severe Aplastic Anemia Patients
    Official Title
    Outcome of Peripheral Blood Allogenic Stem Cell Transplantation Using Non-anti Thymocyte Globulin (ATG ) Conditioning Regimens in Severe Aplastic Anemia Patients
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    November 2018
    Overall Recruitment Status
    Unknown status
    Study Start Date
    January 1, 2019 (Anticipated)
    Primary Completion Date
    December 1, 2019 (Anticipated)
    Study Completion Date
    June 2020 (Anticipated)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Principal Investigator
    Name of the Sponsor
    Assiut 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
    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.

    6. Conditions and Keywords

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

    7. Study Design

    Primary Purpose
    Treatment
    Study Phase
    Phase 2, Phase 3
    Interventional Study Model
    Single Group Assignment
    Model Description
    severe aplastic anemia patients will receive two different conditioning regimens before doing allogenic stem cell transplantation
    Masking
    None (Open Label)
    Allocation
    Randomized
    Enrollment
    50 (Anticipated)

    8. Arms, Groups, and Interventions

    Arm Title
    Non ATG regimen
    Arm Type
    Experimental
    Arm Description
    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
    Arm Title
    ATG regimen
    Arm Type
    Experimental
    Arm Description
    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
    Intervention Type
    Drug
    Intervention Name(s)
    Non ATG Conditioning regimen
    Intervention Description
    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
    Intervention Name(s)
    GVHD Prophylaxis
    Intervention Description
    Cyclosporine A (CsA 3 mg/kg) start day +5
    Intervention Type
    Procedure
    Intervention Name(s)
    Allogenic Stem Cell Transplantation
    Intervention Description
    using peripheral blood stem cells
    Intervention Type
    Drug
    Intervention Name(s)
    ATG conditioning regimen
    Intervention Description
    the other 50% of the patients will receive Cyclophosphamide + ATG
    Primary Outcome Measure Information:
    Title
    Overall Survival rate
    Time Frame
    two years
    Secondary Outcome Measure Information:
    Title
    GVHD occurrence (Acute or Chronic), engraftment and transplant related mortality
    Time Frame
    two years
    Title
    Relapse rate
    Time Frame
    two years
    Title
    Progression free survival
    Time Frame
    two years

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    16 Years
    Maximum Age & Unit of Time
    50 Years
    Accepts Healthy Volunteers
    No
    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.
    Central Contact Person:
    First Name & Middle Initial & Last Name or Official Title & Degree
    Osama A Ibraheim, MD
    Phone
    00201006372498
    Email
    oibrahiem@yahoo.com
    First Name & Middle Initial & Last Name or Official Title & Degree
    Rania M Hafez, MD
    Phone
    00201000019198
    Email
    raniahafez@ymail.com

    12. IPD Sharing Statement

    Citations:
    PubMed Identifier
    26568159
    Citation
    Killick SB, Bown N, Cavenagh J, Dokal I, Foukaneli T, Hill A, Hillmen P, Ireland R, Kulasekararaj A, Mufti G, Snowden JA, Samarasinghe S, Wood A, Marsh JC; British Society for Standards in Haematology. Guidelines for the diagnosis and management of adult aplastic anaemia. Br J Haematol. 2016 Jan;172(2):187-207. doi: 10.1111/bjh.13853. Epub 2015 Nov 16. No abstract available. Erratum In: Br J Haematol. 2016 Nov;175(3):546.
    Results Reference
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    PubMed Identifier
    26529866
    Citation
    George B, Mathews V, Viswabandya A, Abraham A, Ganapule A, Fouzia NA, Korula A, Lakshmi KN, Chandy M, Srivastava A. Immunosuppressive Therapy and Bone Marrow Transplantation for Aplastic Anaemia--The CMC Experience. J Assoc Physicians India. 2015 Mar;63(3 Suppl):36-40.
    Results Reference
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    PubMed Identifier
    25976466
    Citation
    Barone A, Lucarelli A, Onofrillo D, Verzegnassi F, Bonanomi S, Cesaro S, Fioredda F, Iori AP, Ladogana S, Locasciulli A, Longoni D, Lanciotti M, Macaluso A, Mandaglio R, Marra N, Martire B, Maruzzi M, Menna G, Notarangelo LD, Palazzi G, Pillon M, Ramenghi U, Russo G, Svahn J, Timeus F, Tucci F, Cugno C, Zecca M, Farruggia P, Dufour C, Saracco P; Marrow Failure Study Group of the Pediatric Haemato-Oncology Italian Association. Diagnosis and management of acquired aplastic anemia in childhood. Guidelines from the Marrow Failure Study Group of the Pediatric Haemato-Oncology Italian Association (AIEOP). Blood Cells Mol Dis. 2015 Jun;55(1):40-7. doi: 10.1016/j.bcmd.2015.03.007. Epub 2015 Mar 31.
    Results Reference
    background
    PubMed Identifier
    24319167
    Citation
    Socie G. Allogeneic BM transplantation for the treatment of aplastic anemia: current results and expanding donor possibilities. Hematology Am Soc Hematol Educ Program. 2013;2013:82-6. doi: 10.1182/asheducation-2013.1.82.
    Results Reference
    background
    PubMed Identifier
    18706160
    Citation
    Wu Y, Yu J, Zhang L, Luo Q, Xiao JW, Liu XM, Xian Y, Dai BT, Xu YH, Su YC. [Hematopoiesis support of mesenchymal stem cells in children with aplastic anemia]. Zhongguo Dang Dai Er Ke Za Zhi. 2008 Aug;10(4):455-9. Chinese.
    Results Reference
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    PubMed Identifier
    12176866
    Citation
    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.
    Results Reference
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    PubMed Identifier
    11846353
    Citation
    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.
    Results Reference
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    Peripheral Blood Allogenic Stem Cell Transplantation Using Non-anti Thymocyte Globulin Regimens in Severe Aplastic Anemia Patients

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