Sickle Cell DiseaseNCT05249452
Adding Azathioprine/Hydroxyurea Preconditioning to Alemtuzumab/TBI to Reduce Risk of Graft Failure in MSD HSCT in Adult SCD Patients
An observational study of Sickle Cell Disease, run by Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA) at 1 site in Netherlands.
Trial 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. Read more about this study
- Who is it for?
- Ages 16 to 60 years
- Conditions the study is for
- Sickle Cell Disease
- What is being tested?
- Preconditioning with azathiprine and hydroxyurea (3 months)
- How many people
- 20 participants
- Where
- 1 siteNetherlands
- Study dates
- 8 Mar 2018to 1 Dec 2024
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 16 to 60 years
- All sexes
- No healthy volunteers
- Child, Adult
Study population: Sickle cell disease patients, 16 years and older, with an available matched sibling donor.
Who may be able to join
- 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.
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country.
About this study
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
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.
Read the detailed description
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.
Protocol was amended: in the case of impending graft rejection, defined as declining T-cell chimerism in combination with new onset cytopenias, a second course of alemtuzumab 1mg/kg can be administered in order to avert overt graft failure.
- Conditions
- Sickle Cell Disease
- Being tested
- Preconditioning with azathiprine and hydroxyurea (3 months)
- Keywords
- Sickle Cell Disease, Allogeneic stem cell transplantation, Mixed chimerism
- Medical subject headings
- Anemia, Sickle Cell
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
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.
| Study group | Role | What they receive |
|---|---|---|
| Adult transplant-eligible SCD patients with a MSD | Sickle cell disease patients aged 16 years and older with an available matched sibling donor. Receives: Other: Preconditioning with azathiprine and hydroxyurea (3 months) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Disease-free survival
Measured: 1 year post-transplantation
Secondary outcomes (7)
Transplantation-related complications
Measured: Day 100 post-transplantation
Transplantation-related complications
Measured: 1 year post-transplantation
Attenuation of SCD-related organ complications
Measured: 1 year post-transplantation
Percentage of donor myeloid chimerism
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.
Measured: 2 years post-transplantation
Percentage of donor T-cell chimerism
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.
Measured: 2 years post-transplantation
Primary graft failure
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.
Measured: day 42 post-transplantation
Secondary graft failure
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.
Measured: 2-years post-transplantation
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Feb 2022
- Study start8 Mar 2018
- Primary completion1 Dec 2023
- Study completion1 Dec 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Sickle Cell DiseaseStudies of the same condition, open and under way.
- More trials run by Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 20 participants (actual)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Erfan Nur, Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
- Investigators
- Erfan Nur, MD, PhD, Principal investigator, Amsterdam UMC
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05249452
- Sponsor's protocol ID
- W21_160
- Status last verified
- Sep 2025
- First submitted
- 6 Jan 2022
- Last updated
- 2 Oct 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
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.
PubMed 38733340
Study at a glance
From the registry record, last updated by the sponsor on 2 Oct 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT05249452
- Acronym / sponsor ID
- W21_160
- Conditions
- Sickle Cell Disease
- Keywords
- Sickle Cell Disease, Allogeneic stem cell transplantation, Mixed chimerism
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 20 participants (actual)
- Lead sponsor
- Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)University, hospital or other
- Study start
- 8 Mar 2018 (actual)
- Primary completion
- 1 Dec 2023 (actual)
- Study completion
- 1 Dec 2024 (actual)
- First posted
- 21 Feb 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
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.
Protocol was amended: in the case of impending graft rejection, defined as declining T-cell chimerism in combination with new onset cytopenias, a second course of alemtuzumab 1mg/kg can be administered in order to avert overt graft failure.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Adult transplant-eligible SCD patients with a MSD | – | Other: Preconditioning with azathiprine and hydroxyurea (3 months)Sickle cell disease patients aged 16 years and older with an available matched sibling donor. |
Who may qualify
- Ages
- 16 to 60 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
- Study population
- Sickle cell disease patients, 16 years and older, with an available matched sibling donor.
Key inclusion criteria (6 listed)
- 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.
Key exclusion criteria (7 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| 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. | Other | Adult transplant-eligible SCD patients with a MSD |
Primary outcome
Disease-free survival
Time frame: 1 year post-transplantation
7 secondary outcomes
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
Percentage of donor T-cell chimerism
Time frame: 2 years post-transplantation
Primary graft failure
Time frame: day 42 post-transplantation
Secondary graft failure
Time frame: 2-years post-transplantation
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Oct 2025.
- Derived from this study: PubMed 38733340Dovern 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.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Erfan Nur, MD, PhD principal investigator
Amsterdam UMC
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Sickle Cell Disease, run by Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA) at 1 site in Netherlands.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 2 Oct 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Disease-free survival (time frame: 1 year post-transplantation). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05249452, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Oct 2025.