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Trial record 2 of 39 for:    GM-CSF post transplant cyclophosphamide

A Novel TBI Free Conditioning Protocol for Haploidentical Transplant in Acquired Aplastic Anemia: (FluCAB-Prime)

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ClinicalTrials.gov Identifier: NCT03955601
Recruitment Status : Recruiting
First Posted : May 20, 2019
Last Update Posted : August 11, 2020
Sponsor:
Information provided by (Responsible Party):
National Institute of Blood and Marrow Transplant (NIBMT), Pakistan

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

Condition or disease Intervention/treatment Phase
Aplastic Anemia Idiopathic Drug: Haploidentical HSCT using TBI free regimen, ''ATG'' with ''Post transplant cyclophosphamide'' Phase 2

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cohort of 1324 patients 64 % patient are younger than 24 years of age and 87% patients younger than 40 years (unpublished data).There is no donor registry in Pakistan and patients lacking sibling match donor cannot proceed to stem cell transplant due lack of matched unrelated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

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 30 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Novel TBI Free Conditioning Protocol for Haploidentical Hematopoeitic Stem Cell Transplant in Acquired Aplastic Anemia
Actual Study Start Date : July 12, 2018
Estimated Primary Completion Date : December 30, 2020
Estimated Study Completion Date : June 30, 2021

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: TBI free Haploidentical HSCT
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.
Drug: Haploidentical HSCT using TBI free regimen, ''ATG'' with ''Post transplant cyclophosphamide''
''Busulphan'' will be used in place of ''TBI'' in equivalent myelotoxic dose to facilitate engraftment , ''ATG'' will be used to reduce GVHD and facilitate engraftment while ''combine PBSC'' and/OR ''Bone marrow harvest'' will be used
Other Name: ''Combined BMH'' and ''PBSC harvest''




Primary Outcome Measures :
  1. Number of Participants with overall survival [ Time Frame: from the date of transplant to 1 year post transplant ]
    overall survival is defined as the time interval from date of transplant to death or to last follow-up, whichever occurs first.


Secondary Outcome Measures :
  1. Number of Participants with Disease free survival [ Time Frame: from the date of transplant to 1 year post transplant ]
    from time of transplant to death or last follow up

  2. Time of Neutrophil engraftment [ Time Frame: from the date of transplant to 10 to day 28 post transplant ]
    first of 3 consecutive days with Absolute neutrophil count> 0.5

  3. Frequency of Graft versus host disease [ Time Frame: from the date of transplant to acute upto 100 day post transplant, chronic >100 days post transplant ]
    as per clinical and histopathological diagnosis

  4. Rate of Complications [ Time Frame: from the date of transplant to 1 year from day of transplantation ]
    both infectious and non infectious



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Ages Eligible for Study:   2 Years to 60 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03955601


Contacts
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Contact: Xanab akram 03325346564 xanab.akram@gmail.com

Locations
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Pakistan
NIBMT Recruiting
Rawalpindi, Punjab, Pakistan, 46000
Contact: Tariq Mehmood Satti, FCPS, MCPS    +92-51-9270076 ext 201    tariqmahmood_satti@yahoo.com   
Contact: FCPS,FACP         
Sub-Investigator: Xanab Akram         
Sponsors and Collaborators
National Institute of Blood and Marrow Transplant (NIBMT), Pakistan
Investigators
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Study Chair: Tariq Mehmood Satti, FCPS NIBMT
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Responsible Party: National Institute of Blood and Marrow Transplant (NIBMT), Pakistan
ClinicalTrials.gov Identifier: NCT03955601    
Other Study ID Numbers: AFBMTC-HAPLO-AA
First Posted: May 20, 2019    Key Record Dates
Last Update Posted: August 11, 2020
Last Verified: August 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
Keywords provided by National Institute of Blood and Marrow Transplant (NIBMT), Pakistan:
haploidentical
Aplastic anemia
TBI
Additional relevant MeSH terms:
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Cyclophosphamide
Anemia
Anemia, Aplastic
Hematologic Diseases
Bone Marrow Diseases
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists