Testing Abatacept with Sirolimus for thalassemia in children

Exclusion

• −Patients with a known life-threatening allergy to components of the pre transplant immunosuppression (fludarabine), conditioning (treosulfan, cyclophosphamide or anti-thymocyte globulin) or graft versus host prophylactic regimen (abatacept, sirolimus).
• −Must not be allergic to granulocyte colony stimulating factor (G-CSF)
• −Active HIV, hepatitis B or hepatitis C disease.
• −Evidence of active, deep seated, life-threatening infections despite therapy (e.g., certain fungal species, HIV, etc.).
• −The recipient who meets any of the following criteria will be excluded from participation in this study:
• −Patients will not be excluded based on sex, race, or ethnic background.
• −Patients will be excluded if they demonstrate significant functional deficits in major organs, which could interfere with the outcome following bone marrow transplant, including:
• −Cardiac: Evidence of significant cardiac dysfunction (resting left ventricular ejection fraction of \< 50% with absence of improvement with exercise), marked cardiomegaly or uncontrollable hypertension.
• −Renal: Evidence of \> 50% reduction in expected creatinine clearance or GFR \< 60mL/min/1.73m2
• −Hepatic: Evidence of hepatic dysfunction evidenced by a serum direct (conjugate) bilirubin of \> 2.5 mg/dl, or ALT \> 5 times the upper limit of normal for age.
• −Pulmonary: Evidence of focal or diffuse active infection or pneumonitis and the patient demonstrates a FEV1 \< 50% or carbon monoxide diffusing capacity (DLCO) of \< 50% predicted value (adjusted for hemoglobin). The patient should not require ventilation support.
• −Presence of donor specific antibody (DSA) with mean fluorescence intensity (MFI) greater than 3,000.
• −Previous stem cell transplant or gene therapy.
• −Presence of cardiomyopathy with a T2\* \< 10ms per Cardiac MRI.
• −Presence of significant liver iron deposition defined as liver iron content \>15mg/g liver dry weight. If iron chelation were optimized and reassessment within 6 months shows a decrease of LIC to \<15 with no evidence of cardiomyopathy, patient may still be considered for enrollmentEnrolmentThe number of participants a study plans to include, or has included.Read more →.
• −Severe liver cirrhosis or bridging fibrosis on liver biopsy if previously done.
• −Prior or current malignancy or myeloproliferative or immunodeficiency disorder.
• −Any condition that would preclude serial follow upFollow-upContinued check-ins after the treatment part is finished.Read more →.
• −Any condition or diagnosis, that could in the opinion of the Principal InvestigatorPrincipal investigatorThe doctor or researcher responsible for running the study at a site.Read more → or delegate interfere with the participant's ability to comply with study instructions, might confound the interpretation of the study results, or put the participant at risk
• −Donor EligibilityEligibility criteriaThe full list of requirements for taking part in a study.Read more →:
• −Donors will not be considered research subjects as the stem cell collection procedure is standard of careStandard of careThe treatment normally given for a condition outside a study.Read more → and will not be considered part of the research.
• −In order to be eligible to participate in this study, the donor must meet all of the following criteria:
• −May have thalassemia or sickle trait.
• −Will also consider ABO match and lack of donor specific anti-HLA antibodies.
• −Donors must be minimal of 15 kg weight and have completed routine donor evaluations as per our standard of care.
• −Donors must have signed (by patient or legal guardian) informed consentInformed consentThe process of being told what taking part involves, then choosing freely.Read more → for the protocolProtocolThe detailed plan a study must follow.Read more → approved by the Research Ethical Board of the Hospital for Sick Children/University of Toronto.
• −No evidence of transmissible diseases in compliance with the Health Canada CTO regulations
• −Patients will be excluded if they are women of childbearing potential who are currently pregnant (b-HCG+) or who are not practicing adequate contraception.
• −Not pregnant or lactating