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

Primary Purpose

Aplastic Anemia Idiopathic

Status
Unknown status
Phase
Phase 2
Locations
Pakistan
Study Type
Interventional
Intervention
Haploidentical HSCT using TBI free regimen, ''ATG'' with ''Post transplant cyclophosphamide''
Sponsored by
National Institute of Blood and Marrow Transplant (NIBMT), Pakistan
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Aplastic Anemia Idiopathic focused on measuring haploidentical, Aplastic anemia, TBI

Eligibility Criteria

2 Years - 60 Years (Child, Adult)All SexesDoes not accept healthy volunteers

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)

Sites / Locations

  • NIBMTRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

TBI free Haploidentical HSCT

Arm 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.

Outcomes

Primary Outcome Measures

Number of Participants with overall survival
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

Number of Participants with Disease free survival
from time of transplant to death or last follow up
Time of Neutrophil engraftment
first of 3 consecutive days with Absolute neutrophil count> 0.5
Frequency of Graft versus host disease
as per clinical and histopathological diagnosis
Rate of Complications
both infectious and non infectious

Full Information

First Posted
April 22, 2019
Last Updated
August 8, 2020
Sponsor
National Institute of Blood and Marrow Transplant (NIBMT), Pakistan
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1. Study Identification

Unique Protocol Identification Number
NCT03955601
Brief Title
A Novel TBI Free Conditioning Protocol for Haploidentical Transplant in Acquired Aplastic Anemia:
Acronym
FluCAB-Prime
Official Title
A Novel TBI Free Conditioning Protocol for Haploidentical Hematopoeitic Stem Cell Transplant in Acquired Aplastic Anemia
Study Type
Interventional

2. Study Status

Record Verification Date
August 2020
Overall Recruitment Status
Unknown status
Study Start Date
July 12, 2018 (Actual)
Primary Completion Date
December 30, 2020 (Anticipated)
Study Completion Date
June 30, 2021 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
National Institute of Blood and Marrow Transplant (NIBMT), Pakistan

4. Oversight

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
Data Monitoring Committee
Yes

5. Study Description

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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Aplastic Anemia Idiopathic
Keywords
haploidentical, Aplastic anemia, TBI

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
30 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
TBI free Haploidentical HSCT
Arm Type
Experimental
Arm 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.
Intervention Type
Drug
Intervention Name(s)
Haploidentical HSCT using TBI free regimen, ''ATG'' with ''Post transplant cyclophosphamide''
Other Intervention Name(s)
''Combined BMH'' and ''PBSC harvest''
Intervention Description
''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
Primary Outcome Measure Information:
Title
Number of Participants with overall survival
Description
overall survival is defined as the time interval from date of transplant to death or to last follow-up, whichever occurs first.
Time Frame
from the date of transplant to 1 year post transplant
Secondary Outcome Measure Information:
Title
Number of Participants with Disease free survival
Description
from time of transplant to death or last follow up
Time Frame
from the date of transplant to 1 year post transplant
Title
Time of Neutrophil engraftment
Description
first of 3 consecutive days with Absolute neutrophil count> 0.5
Time Frame
from the date of transplant to 10 to day 28 post transplant
Title
Frequency of Graft versus host disease
Description
as per clinical and histopathological diagnosis
Time Frame
from the date of transplant to acute upto 100 day post transplant, chronic >100 days post transplant
Title
Rate of Complications
Description
both infectious and non infectious
Time Frame
from the date of transplant to 1 year from day of transplantation

10. Eligibility

Sex
All
Minimum Age & Unit of Time
2 Years
Maximum Age & Unit of Time
60 Years
Accepts Healthy Volunteers
No
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)
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Xanab akram
Phone
03325346564
Email
xanab.akram@gmail.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Tariq Mehmood Satti, FCPS
Organizational Affiliation
NIBMT
Official's Role
Study Chair
Facility Information:
Facility Name
NIBMT
City
Rawalpindi
State/Province
Punjab
ZIP/Postal Code
46000
Country
Pakistan
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Tariq Mehmood Satti, FCPS, MCPS
Phone
+92-51-9270076
Ext
201
Email
tariqmahmood_satti@yahoo.com
First Name & Middle Initial & Last Name & Degree
FCPS,FACP
First Name & Middle Initial & Last Name & Degree
Xanab Akram

12. IPD Sharing Statement

Plan to Share IPD
No

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