Using Azathioprine and Hydroxyurea to Improve Stem Cell Transplant Outcomes in Sickle Cell Disease
Adding Azathioprine/Hydroxyurea Preconditioning to Alemtuzumab/TBI to Reduce Risk of Graft Failure in Matched Sibling Donor Allogeneic HSCT in Adult Sickle Cell Patients
This study is testing if adding azathioprine and hydroxyurea before a stem cell transplant can help adults with sickle cell disease have better outcomes and reduce the need for certain medications after the transplant.
Quick facts
| Study type | Observational |
|---|---|
| Enrollment | 20 (estimated) |
| Ages | 16 Years to 60 Years |
| Sex | All |
| Sponsor | Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA) Academic / other |
| Drugs / interventions | alemtuzumab |
| Locations | 1 site (Amsterdam) |
| Trial ID | NCT05249452 on ClinicalTrials.gov |
What this trial studies
This study investigates the effects of a 3-month preconditioning regimen with azathioprine and hydroxyurea added to alemtuzumab and total body irradiation (TBI) in adult patients with sickle cell disease undergoing matched sibling donor stem cell transplantation. The goal is to enhance disease-free survival and increase donor chimerism, thereby reducing the risk of graft failure. The study will also assess whether this preconditioning allows for a reduction or discontinuation of sirolimus, an immunosuppressive medication, at 12 months post-transplantation. The approach is based on previous findings in thalassemia patients, aiming to improve outcomes in a population with unique challenges related to hemoglobinopathies.
Who should consider this trial
Good fit: Ideal candidates are adults aged 16 to 60 with sickle cell disease who have an HLA-identical matched sibling donor and a good performance status.
Not a fit: Patients with poor performance status, significant cardiac or pulmonary dysfunction, or those who are HIV-positive may not benefit from this study.
Why it matters
Potential benefit: If successful, this approach could significantly improve transplant outcomes and reduce the need for long-term immunosuppression in sickle cell disease patients.
How similar studies have performed: Previous studies have shown success with similar preconditioning approaches in thalassemia, but this specific application in sickle cell disease is novel.
Eligibility criteria
Show full inclusion / exclusion criteria
Inclusion Criteria: * SCD patients with an HLA-identical matched sibling donor eligible for allogeneic stem cell transplantation. * Age 16 - 60 years * Good performance status (ECOG 0 or 1; Karnofsky and Lansky 70-100) * Patients and donors (MSD) must be able to sign consent forms for receiving and donating hematopoietic stem cells respectively. The sibling donor should be willing to donate. * Patients must be geographically accessible and willing to participate in all stages of treatment. * Eligible diagnoses: Patients with sickle cell disease such as sickle cell anemia (Hb SS), Hb/Sβ0-thalassemia, Hb/Sβ+-thalassemia, HbSC disease, HbSE disease, HbSD disease and Hemoglobin SO- Arab disease. Exclusion Criteria: * Poor performance status (ECOG\>1). * Poor cardiac function: left ventricular ejection fraction\<35%. * Poor pulmonary function: FEV1 and FVC\<40% predicted. * Poor liver function: direct bilirubin \>3.1 mg/dl * HIV-positive * Women of childbearing potential who currently are pregnant (Beta-HCG+) or who are not practicing adequate contraception. * Patients who have any debilitating medical or psychiatric illness that would preclude their giving informed consent or their receiving optimal treatment and follow-up. However, patients with history of stroke and significant cognitive deficit, that would preclude giving informed consent or assent will not be excluded, if they have a family member or significant other with Power of Attorney to also consent of their behalf.
Where this trial is running
Amsterdam
- Amsterdam Medical Centre — Amsterdam, Netherlands (Recruiting)
Study contacts
- Principal investigator: Erfan Nur, MD, PhD — Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
- Study coordinator: Erfan Nur, MD, PhD
- Email: e.nur@amsterdamumc.nl
- Phone: 0031-20 - 4442604
How to participate
- Review the eligibility criteria above with your treating physician.
- Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
- Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.