A Novel TBI Free Conditioning Protocol for Haploidentical Transplant in Acquired Aplastic Anemia:

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Brief Title

A Novel TBI Free Conditioning Protocol for Haploidentical Transplant in Acquired Aplastic Anemia:

Official Title

A Novel TBI Free Conditioning Protocol for Haploidentical Hematopoeitic Stem Cell Transplant in Acquired Aplastic Anemia

Brief Summary

      Severe and very severe aplastic anemia are life threatening disorders for which allogeneic
      stem cell transplant is only curative treatment. However, matched sibling donor (MSD) is
      available in only 25-35% cases. Pakistan has a population of around 203 million but there is
      no donor registry available so there is no option available for matched unrelated donor (MUD)
      transplants . Haploidentical transplant represents only curative option for patients lacking
      MSD. Protocols involving post transplant cyclophosphamide require Total body irradiation
      (TBI) and utilize peripheral blood stem cell(PBSC) as graft source. TBI is not available in
      most of transplant centres across Pakistan due to lack of availability , cost and lack of
      expertise. The investigators have conceived a novel TBI free conditioning regimen to be used
      for haplo-identical Hemtopoeitic stem cell transplant in acquired aplastic anemia patients
    

Detailed Description

      Aplastic anemia is considered to be a rare and heterogenous disease with incidence of 1-2 per
      million in western countries. Data from Asian studies show a 3-4 fold higher
      incidence.Majority of newly diagnosed aplastic anemia patients are younger and in Armed
      forces bone marrow transplant cohort of 1324 patients 64 % patient are younger than 24 years
      of age and 87% patients younger than 40 years (unpublished data).There is no donor registry
      in Pakistan and patients lacking sibling match donor cannot proceed to stem cell transplant
      due lack of matched unrelated donors. Horse antithymocyte globulin is not available currently
      in Pakistan and response to Rabbit antithymocyte globulin is dismal as shown in number of
      international studies. So haploidentical stem cell transplant remains only curative option
      for patients lacking Matched sibling donor. Currently there are 2 major platforms used for
      haplo-identical stem cell transplant. Post transplant cyclophosphamide based using TBI and
      haplo regimen of Peking university. TBI is not available for most of our patients in Pakistan
      due to cost,non-availability and lack of expertise. The investigators have formulated a novel
      TBI free regimen incorporating Busulphan, antithymocyte globulin and using co-primed bone
      marrow and peripheral blood harvest to minimize graft-versus-host disease and facilitate
      engraftment. Post transplant cyclophosphamide, Cyclosporine and mycophenolate mofetil will be
      used for graft-versus-host disease prophylaxis
    

Study Phase

Phase 2

Study Type

Interventional


Primary Outcome

Number of Participants with overall survival

Secondary Outcome

 Number of Participants with Disease free survival

Condition

Aplastic Anemia Idiopathic

Intervention

Haploidentical HSCT using TBI free regimen, ''ATG'' with ''Post transplant cyclophosphamide''

Study Arms / Comparison Groups

 TBI free Haploidentical HSCT
Description:  Recipients will receive a reduced intensity conditioning regimen of ''Fludarabine'' 30 mg/m2 IV daily from day -7 to -3, ''Cyclophosphamide'' 14.5-30 mg/kg IV daily on day -6 and -5 , ''rabbit Antithymocyte globulin'' 5 mg /kg/day from day -6 to day-3; ''Busulphan'' IV 3.2 mg per kg/day in 02 divided doses on day -3 and day-2, ''Granulocyte Colony Stimulating factor primed Bone marrow harvest'' and/OR ''PBSC'' graft on day 0 and day +1 respectively and Graft versus host disease prophylaxis with ''post-transplant cyclophosphamide'' administered at a dose of 50mg/kg/day given daily on days +3 and +5 post-transplant and ''cyclosporine'' from day +5, ''mycophenolate mofetil'' from day+5 to day+35.

Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information


Recruitment Status

Drug

Estimated Enrollment

30

Start Date

July 12, 2018

Completion Date

June 30, 2021

Primary Completion Date

December 30, 2020

Eligibility Criteria

        Inclusion Criteria:

          -  Age >2 years and < 60 years

          -  Karnofsky performance status >= 70%

          -  Aplastic Anemia that meets the following criteria:

             i. Peripheral Blood (must fulfill 2 of 3): ii. <500 neutrophils iii. <20,000 platelets
             iv. absolute reticulocyte count <40,000/microL

          -  Bone Marrow (must be ): markedly hypocellular (<25% of normal cellularity) with
             absence of reticulin and abnormal infiltrate

        Exclusion Criteria:

          -  Presence of donor specific antibodies

          -  Fanconi anemia

          -  Cytogenetic abnormalities suggestive of myelodysplastic syndrome

          -  Prior HSCT

          -  Human immunodeficiency virus infection

          -  Active Hepatitis B virus infection

          -  Active /uncontrolled bacterial, viral , fungal infection or Tuberculosis

          -  Psychiatric illness

          -  Poor cardiac function (ejection fraction <40%)

          -  Poor pulmonary function (Forced vital capacity <50% predicted)

          -  Poor liver function (bilirubin >= 2mg/dL)

          -  Poor renal function (creatinine >= 2.0mg/dL or creatinine clearance <40)
      

Gender

All

Ages

2 Years - 60 Years

Accepts Healthy Volunteers

No

Contacts

Tariq Mehmood Satti, FCPS, 03325346564, [email protected]

Location Countries

Pakistan

Location Countries

Pakistan

Administrative Informations


NCT ID

NCT03955601

Organization ID

AFBMTC-HAPLO-AA


Responsible Party

Sponsor

Study Sponsor

National Institute of Blood and Marrow Transplant (NIBMT), Pakistan


Study Sponsor

Tariq Mehmood Satti, FCPS, Study Chair, NIBMT


Verification Date

August 2020