Do Alemtuzumab Levels Predict T Cell Chimerism After MSD SCT for SCD?

NCT ID: NCT05905770

Last Updated: 2023-06-22

Basic Information

• Recruitment Status: RECRUITING
• Total Enrollment: 20 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2022-07-15
• Study Completion Date: 2025-11-30

Brief Summary

Rationale: Non-myeloablative allogeneic stem cell transplantation (SCT) has become a feasible curative treatment option for sickle cell disease (SCD) patients with an available matched sibling donor. Chemotherapy free conditioning with alemtuzumab and 3 Gy total body irradiation (TBI) is increasingly being used as preferred conditioning scheme for these patients. This regimen typically results in mixed donor chimerism and has only few toxic effects. However, the risk of graft failure (rejection) is still significant, with an occurrence of 13% in the latest series. Levels of T cell chimerism are crucial for the success of this kind of transplantation. A donor T cell level of at least 50% at 1-year post-transplantation seems to be sufficient to allow the discontinuation of immunosuppressive medication without risk of graft rejection. Low levels of alemtuzumab prior to or shortly after SCT are thought to facilitate rejection of the donor graft. Recently, a positive correlation between alemtuzumab levels on day+14 was found with levels of T cell chimerism +2 and +4 months post-transplantation in adult SCD patients receiving matched sibling donor SCT. However, in this study alemtuzumab levels prior to the infusion of hematopoietic stem cells and beyond day +28 post-transplantation were not measured. Furthermore, the alemtuzumab levels were measured in 2 patient groups undergoing two different conditioning regimens.

Here, the investigators aim to thoroughly investigate the correlation of alemtuzumab levels and T cell chimerism. This will be the first study involving SCD patients receiving matched sibling donor SCT with alemtuzumab/TBI conditioning that includes alemtuzumab level measurements before the infusion of hematopoietic stem cells and beyond 1-month post-transplantation. Findings from this study will improve the insights into the etiology of graft failure in these patients and might ultimately lead to a more personalized approach in dosing alemtuzumab in order to achieve a more robust and stable engraftment of donor hematopoietic stem cells.

Objectives: To investigate whether serum alemtuzumab concentrations are predictive of the robustness of engraftment in SCD patients undergoing a matched sibling donor transplantation with alemtuzumab/TBI conditioning resulting in mixed chimerism.

Study design: Prospective observational laboratory study. Serum alemtuzumab concentration will be measured at various time points before and after stem cell infusion (days -3, 0, +7, +14, +28, +60).

Study population: Adult SCD patients that are planned for a matched sibling donor transplantation with alemtuzumab/TBI conditioning at the Amsterdam UMC.

Main study parameters/endpoints: The correlation between serum alemtuzumab concentration and levels of donor chimerism. Secondary endpoints: correlation between serum alemtuzumab levels and patients with and without successful engraftment. Correlation of serum alemtuzumab levels and the dosing of alemtuzumab in mg/kg, number of patient lymphocyte count and total number of infused enucleated donor-derived cells.

Conditions

Sickle Cell Disease

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: PROSPECTIVE

Study Groups

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

Alemtuzumab 1mg/kg/TBI 3Gy conditioning

Alemtuzumab Injection [Campath]

Intervention Type: DRUG

Alemtuzumab 1mg/kg

Interventions

Alemtuzumab Injection [Campath]

Alemtuzumab 1mg/kg

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Age 16 years and older
• High performance liquid chromatography (HPLC) confirmed diagnoses of SCD (all genotypes)
• Planned for a non-myeloablative matched sibling donor SCT with alemtuzumab/TBI at the Amsterdam UMC
• Willing and able to provide written informed consent

• Minimum Eligible Age: 16 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Leiden University Medical Center

OTHER

Sponsor Role: collaborator

Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)

OTHER

Sponsor Role: lead

Responsible Party

Erfan Nur

Prinicpal investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Erfan Nur, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)

Locations

Amsterdam Medical Centre

Amsterdam, , Netherlands

Site Status: RECRUITING

Countries

Netherlands

Central Contacts

Erfan Nur, MD, PhD

Role: CONTACT

e.nur@amsterdamumc.nl

0031-20 - 4442604

Facility Contacts

Erfan Nur, MD, PhD

Role: primary

e.nur@amsterdamumc.nl

0031-20-4442604

Other Identifiers

METC 2022_0189

Identifier Type: -

Identifier Source: org_study_id