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

NCT ID: NCT03955601

Last Updated: 2020-08-11

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE2
• Total Enrollment: 30 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-07-12
• Study Completion Date: 2021-06-30

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cohort of 1324 patients 64 % patient are younger than 24 years of age and 87% patients younger than 40 years (unpublished data).There is no donor registry in Pakistan and patients lacking sibling match donor cannot proceed to stem cell transplant due lack of matched unrelated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

Conditions

Aplastic Anemia Idiopathic

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

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

Intervention Type: 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

Interventions

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

Intervention Type: DRUG

Other Intervention Names

''Combined BMH'' and ''PBSC harvest''

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)

• Minimum Eligible Age: 2 Years
• Maximum Eligible Age: 60 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

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

OTHER_GOV

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Tariq Mehmood Satti, FCPS

Role: STUDY_CHAIR

NIBMT

Locations

NIBMT

Rawalpindi, Punjab Province, Pakistan

Site Status: RECRUITING

Countries

Pakistan

Central Contacts

Xanab akram

Role: CONTACT

xanab.akram@gmail.com

03325346564

Facility Contacts

Tariq Mehmood Satti, FCPS, MCPS

Role: primary

tariqmahmood_satti@yahoo.com

+92-51-9270076 ext. 201

FCPS,FACP

Role: backup

Other Identifiers

AFBMTC-HAPLO-AA

Identifier Type: -

Identifier Source: org_study_id