Adding Azathioprine/Hydroxyurea Preconditioning to Alemtuzumab/TBI to Reduce Risk of Graft Failure in MSD HSCT in Adult SCD Patients

NCT05249452 | Completed

• 1 other identifier: W21_160
• Study Type: observational
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

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. Furthermore, the investigators will evaluate whether azathioprine/hydroxyurea preconditioning leads to more patients being able to taper and discontinue sirolimus at 12 months post-transplantation.

Conditions

Sickle Cell Disease

Keywords

Sickle Cell Disease; Allogeneic stem cell transplantation; Mixed chimerism

Outcome Measures

Primary Outcomes (1)

• Disease-free survival

  1 year post-transplantation

Secondary Outcomes (7)

• Transplantation-related complications

  Day 100 post-transplantation

• Transplantation-related complications

  1 year post-transplantation

• Attenuation of SCD-related organ complications

  1 year post-transplantation

• Percentage of donor myeloid chimerism

  2 years post-transplantation

• Percentage of donor T-cell chimerism

  2 years post-transplantation

Study Arms (1)

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)

Interventions

Preconditioning with azathiprine and hydroxyurea (3 months) OTHER

Preconditioning with azathiprine and hydroxyurea (3 months) before alemtuzumab/TBI conditioning and matched sibling donor allogeneic stem cell transplantation.

Adult transplant-eligible SCD patients with a MSD

Eligibility Criteria

• Age: 16 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)
• Sampling Method: Non-Probability Sample

Study Population

Sickle cell disease patients, 16 years and older, with an available matched sibling donor.

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA): lead

Study Sites (1)

Amsterdam Medical Centre

Amsterdam, Netherlands

Location

Related Publications (1)

• Dovern E, Aydin M, Hazenberg MD, Tang MW, Suijk EM, Hoogendoorn GM, Van Tuijn CFJ, Kerkhoffs JL, Rutten CE, Zeerleder SS, de la Fuente J, Biemond BJ, Nur E. Azathioprine/hydroxyurea preconditioning prior to nonmyeloablative matched sibling donor hematopoietic stem cell transplantation in adults with sickle cell disease: A prospective observational cohort study. Am J Hematol. 2024 Aug;99(8):1523-1531. doi: 10.1002/ajh.27360. Epub 2024 May 11.

  PMID: 38733340 DERIVED

MeSH Terms

Conditions

Anemia, Sickle Cell

Interventions

Hydroxyurea

Condition Hierarchy (Ancestors)

Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Anemia; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemoglobinopathies; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Intervention Hierarchy (Ancestors)

Urea; Amides; Organic Chemicals

Study Officials

• Erfan Nur, MD, PhD

  Amsterdam UMC

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: January 6, 2022
• First Posted: February 21, 2022
• Study Start: March 8, 2018
• Primary Completion: December 1, 2023
• Study Completion: December 1, 2024
• Last Updated: October 2, 2025

Record last verified: 2025-09

Locations

NL (1)