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

NCT03955601 | Unknown Phase 2 DMC

• 1 other identifier: AFBMTC-HAPLO-AA
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

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

Conditions

Aplastic Anemia Idiopathic

Keywords

haploidentical; Aplastic anemia; TBI

Outcome Measures

Primary Outcomes (1)

• 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.

  from the date of transplant to 1 year post transplant

Secondary Outcomes (4)

• Number of Participants with Disease free survival

  from the date of transplant to 1 year post transplant

• Time of Neutrophil engraftment

  from the date of transplant to 10 to day 28 post transplant

• Frequency of Graft versus host disease

  from the date of transplant to acute upto 100 day post transplant, chronic >100 days post transplant

• Rate of Complications

  from the date of transplant to 1 year from day of transplantation

Study Arms (1)

TBI free Haploidentical HSCT

EXPERIMENTAL

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''

Interventions

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

''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

Also known as: ''Combined BMH'' and ''PBSC harvest''

TBI free Haploidentical HSCT

Eligibility Criteria

• Age: 2 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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)

Sponsors & Collaborators

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

Study Sites (1)

NIBMT

Rawalpindi, Punjab Province, 46000, Pakistan

RECRUITING

MeSH Terms

Conditions

Anemia, Aplastic

Condition Hierarchy (Ancestors)

Anemia; Hematologic Diseases; Hemic and Lymphatic Diseases; Bone Marrow Failure Disorders; Bone Marrow Diseases

Study Officials

• Tariq Mehmood Satti, FCPS

  NIBMT

  STUDY CHAIR

Central Study Contacts

Xanab akram

CONTACT

03325346564; xanab.akram@gmail.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER GOV
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 22, 2019
• First Posted: May 20, 2019
• Study Start: July 12, 2018
• Primary Completion: December 30, 2020
• Study Completion: June 30, 2021
• Last Updated: August 11, 2020

Record last verified: 2020-08

Data Sharing

• IPD Sharing: Will not share

Locations

PA (1)