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
About this trial
This is an interventional treatment trial for Severe Aplastic Anemia
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.
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
NCT ID
NCT03295058
First Posted
September 24, 2017
Last Updated
November 24, 2018
Sponsor
Assiut University
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
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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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