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

Aplastic Anemia Idiopathic Clinical Trial

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Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03955601
• Other study ID #: AFBMTC-HAPLO-AA
• Status: Recruiting
• Phase: Phase 2
• Start date: July 12, 2018
• Est. completion date: June 30, 2021

Study information

• Verified date: August 2020
• Source: National Institute of Blood and Marrow Transplant (NIBMT), Pakistan
• Contact: Xanab akram
• Phone: 03325346564
• Email: xanab.akram[@]gmail.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

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cohort of 1324 patients 64 % patient are younger than 24 years of age and 87% patients younger than 40 years (unpublished data).There is no donor registry in Pakistan and patients lacking sibling match donor cannot proceed to stem cell transplant due lack of matched unrelated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

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 30
• Est. completion date: June 30, 2021
• Est. primary completion date: December 30, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 2 Years to 60 Years

Eligibility

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)

Related Conditions & MeSH terms

• Anemia
• Anemia, Aplastic
• Aplastic Anemia Idiopathic

Intervention

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

Locations

Country	Name	City	State
Pakistan	NIBMT	Rawalpindi	Punjab

Sponsors (1)

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

Country where clinical trial is conducted

Pakistan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Number of Participants with Disease free survival	from time of transplant to death or last follow up	from the date of transplant to 1 year post transplant
Secondary	Time of Neutrophil engraftment	first of 3 consecutive days with Absolute neutrophil count> 0.5	from the date of transplant to 10 to day 28 post transplant
Secondary	Frequency of Graft versus host disease	as per clinical and histopathological diagnosis	from the date of transplant to acute upto 100 day post transplant, chronic >100 days post transplant
Secondary	Rate of Complications	both infectious and non infectious	from the date of transplant to 1 year from day of transplantation