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

August 8, 2020 updated by: National Institute of Blood and Marrow Transplant (NIBMT), Pakistan

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

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

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

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cohort of 1324 patients 64 % patient are younger than 24 years of age and 87% patients younger than 40 years (unpublished data).There is no donor registry in Pakistan and patients lacking sibling match donor cannot proceed to stem cell transplant due lack of matched unrelated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

Interventional

Enrollment (Anticipated)

30

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • Pakistan
    • Punjab
      • Rawalpindi, Punjab, Pakistan, 46000
        • Recruiting
        • NIBMT
        • Contact:
        • Contact:
          • FCPS,FACP
        • Sub-Investigator:
          • Xanab Akram

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

2 years to 60 years (Child, Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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)

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / 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 Names:
  • ''Combined BMH'' and ''PBSC harvest''

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
from the date of transplant to 1 year post transplant

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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
from the date of transplant to 1 year post transplant
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
from the date of transplant to 10 to day 28 post transplant
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
from the date of transplant to acute upto 100 day post transplant, chronic >100 days post transplant
Rate of Complications
Time Frame: from the date of transplant to 1 year from day of transplantation
both infectious and non infectious
from the date of transplant to 1 year from day of transplantation

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

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

Investigators

  • Study Chair: Tariq Mehmood Satti, FCPS, NIBMT

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

July 12, 2018

Primary Completion (Anticipated)

December 30, 2020

Study Completion (Anticipated)

June 30, 2021

Study Registration Dates

First Submitted

April 22, 2019

First Submitted That Met QC Criteria

May 16, 2019

First Posted (Actual)

May 20, 2019

Study Record Updates

Last Update Posted (Actual)

August 11, 2020

Last Update Submitted That Met QC Criteria

August 8, 2020

Last Verified

August 1, 2020

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • AFBMTC-HAPLO-AA

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

Drug and device information, study documents

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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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