Adding Azathioprine/Hydroxyurea Preconditioning to Alemtuzumab/TBI to Reduce Risk of Graft Failure in MSD HSCT in Adult SCD Patients
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|ClinicalTrials.gov Identifier: NCT05249452|
Recruitment Status : Recruiting
First Posted : February 21, 2022
Last Update Posted : February 21, 2022
|Condition or disease||Intervention/treatment|
|Sickle Cell Disease||Other: Preconditioning with azathiprine and hydroxyurea (3 months)|
Matched sibling donor (MSD) transplantation with non-myeloablative conditioning (1 mg/kg alemtuzumab and 300 cGy total body irradiation (TBI)) using peripheral blood derived stem cells has shown promising results in adult SCD patients. However, a large part of these patients did not reach complete donor chimerism (especially relatively low T-cell chimerism) with graft failure rates of approximately 13%. Furthermore a significant proportion of sickle cell patients need to continuously use the immunosuppressive medication sirolimus to prevent graft failure due to poor donor T-cell chimerism. Graft failure is more common in sickle cell patients than in patients who are transplanted for hematological malignancies. Due to the continuously active erythropoiesis, patients with hemoglobinopathies, such as thalassemia and SCD, have expanded bone marrow, which negatively affects engraftment. Another reason for graft failure in these patients is a continuously triggered immune system due to chronic hemolysis and inflammation in hemoglobinopathies. To improve engraftment and donor chimerism, a preconditioning with azathioprine (immunosuppressive) and hydroxyurea (suppressing bone marrow expansion) during three months has been added to the actual conditioning with alemtuzumab/TBI. Azathioprine/hydroxyurea preconditioning has been proven effective in allo-SCT in thalassemia.
In this study the investigators will prospectively investigate whether the addition of a 3-months long preconditioning with azathioprine to the alemtuzumab/TBI non-myeloablative conditioning results in improved disease-free survival and donor chimerism after allo-SCT in SCD patients. A secondary objective is to evaluate whether azathioprine/hydroxyurea preconditioning leads to more patients being able to taper and discontinue sirolimus at 12 months post-transplantation.
|Study Type :||Observational|
|Estimated Enrollment :||20 participants|
|Official Title:||Adding Azathioprine/Hydroxyurea Preconditioning to Alemtuzumab/TBI to Reduce Risk of Graft Failure in Matched Sibling Donor Allogeneic HSCT in Adult Sickle Cell Patients|
|Actual Study Start Date :||March 8, 2018|
|Estimated Primary Completion Date :||March 1, 2023|
|Estimated Study Completion Date :||December 1, 2023|
Adult transplant-eligible SCD patients with a MSD
Sickle cell disease patients aged 16 years and older with an available matched sibling donor.
Other: Preconditioning with azathiprine and hydroxyurea (3 months)
Preconditioning with azathiprine and hydroxyurea (3 months) before alemtuzumab/TBI conditioning and matched sibling donor allogeneic stem cell transplantation.
- Disease-free survival [ Time Frame: 1 year post-transplantation ]
- Transplantation-related complications [ Time Frame: Day 100 post-transplantation ]
- Transplantation-related complications [ Time Frame: 1 year post-transplantation ]
- Attenuation of SCD-related organ complications [ Time Frame: 1 year post-transplantation ]
- Percentage of donor myeloid chimerism [ Time Frame: 2 years post-transplantation ]Using genetic profiles of both the patient and the donor, percentages of myeloid (isolated granulocytes) chimerism will be measured periodically to evaluate the level of engraftment.
- Percentage of donor T-cell chimerism [ Time Frame: 2 years post-transplantation ]Using genetic profiles of both the patient and the donor, percentages of T-cell (CD3 cells) chimerism will be measured periodically to evaluate the level of engraftment.
- Primary graft failure [ Time Frame: day 42 post-transplantation ]Defined as never achieving >5% donor whole blood or myeloid chimerism (myeloid is preferable) assessed by bone marrow or peripheral blood chimerism assays by day +42 post-transplant. Second infusion of stem cells is also considered indicative of primary graft failure by day +42 post-transplant.
- Secondary graft failure [ Time Frame: 2-years post-transplantation ]Defined as < 5% donor whole blood or myeloid chimerism (myeloid is preferable) in peripheral blood or bone marrow beyond day +42 post-transplant in patients with prior documentation of hematopoietic recovery with >5% donor cells by day +42 post-transplant. Second infusion of stem cells is also considered indicative of secondary graft failure.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05249452
|Contact: Erfan Nur, MD, PhD||0031-20 - email@example.com|
|Contact: Management hematology||0031-20 - firstname.lastname@example.org|
|Amsterdam Medical Centre||Recruiting|
|Contact: Erfan Nur, MD, PhD 0031-20-4442604 email@example.com|
|Principal Investigator:||Erfan Nur, MD, PhD||Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)|