Adjusting Alemtuzumab Dosing for Bone Marrow Transplantation

Precision Alemtuzumab Dosing for Allogeneic Hematopoietic Cell Transplantation in Non-Malignant Diseases

This study is testing if adjusting the dose of alemtuzumab can help kids and young adults getting a bone marrow transplant have fewer complications and recover better.

Quick facts

• Phase: PHASE2
• Study type: Interventional
• Enrollment: 60 (estimated)
• Sex: All
• Sponsor: Children's Hospital Medical Center, Cincinnati (other)
• Drugs / interventions: alemtuzumab
• Locations: 1 site (Cincinnati, Ohio)
• Trial ID: NCT05501756 on ClinicalTrials.gov

What this trial studies

This study investigates the optimal dosing of alemtuzumab, an antibody used to suppress the immune system, in patients undergoing allogeneic hematopoietic cell transplantation (HCT). The goal is to adjust the alemtuzumab dose to achieve a target concentration of 0.15-0.9 ug/mL on the day of graft infusion, which may reduce the risk of complications such as acute graft versus host disease (GVHD) and mixed chimerism. By monitoring and adjusting the dosage, the study aims to improve immune recovery and overall clinical outcomes for patients. The research will evaluate the effectiveness of this tailored dosing approach in a pediatric and young adult population.

Who should consider this trial

Good fit: Ideal candidates are patients aged 6 weeks to 30 years undergoing allogeneic HCT for non-malignant diseases with an alemtuzumab-containing regimen.

Not a fit: Patients with a history of anaphylaxis to alemtuzumab or those who have not cleared alemtuzumab prior to the preparative regimen may not benefit from this study.

Why it matters

Potential benefit: If successful, this approach could lead to improved outcomes and reduced complications for patients undergoing bone marrow transplantation.

How similar studies have performed: While the specific dosing adjustment approach may be novel, similar studies have shown that tailored immunosuppressive regimens can improve outcomes in HCT.

Eligibility criteria

Inclusion Criteria:

* Patients who are undergoing allogeneic HCT at CCHMC with an alemtuzumab-containing preparative regimen for treatment of a non-malignant disease are eligible.
* For the first 7 patients, patients must have a 10/10 HLA matched related or unrelated stem cell donor, or be receiving a CD34+ selected stem cell product. After the first 7 patients, any donor match may be allowed after data review by the BMT clinicians and the PI.

Exclusion Criteria:

* Patients with a history of anaphylaxis to alemtuzumab.
* Patients who have previously received alemtuzumab and have not cleared alemtuzumab prior to the start of the preparative regimen.
* Life expectancy less than 4 weeks.
* Patients receiving dialysis or plasmapheresis at the time of the start of the conditioning regimen.
* Failure to sign informed consent and/or assent, or inability to undergo informed consent process.
* It is not medically advisable to obtain the specimens necessary for this study.
* Not able to tolerate subcutaneous dosing (patients with severe skin conditions).
* Patients with cancer.
* Patients whose clinical condition suggest there may be inability to successfully perform the PK modeling such as, but not limited to, active flaring of hemophagocytic lymphohistiocytosis in which excessive lymphoproliferation may significantly alter the target-mediated clearance of alemtuzumab and prevent observation of non-target mediated clearance which is needed for robust modeling.
* Patients whose pre-alemtuzumab level reveals an interfering substance which prevents accurate measurement of alemtuzumab.

Where this trial is running

Cincinnati, Ohio

• Cincinnati Children's Hospital Medical Center — Cincinnati, Ohio, United States (RECRUITING)

Study contacts

• Principal investigator: Parinda Mehta, MD — Children's Hospital Medical Center, Cincinnati
• Study coordinator: Caitlin Cottrell

Conditions: Allogeneic Hematopoietic Cell Transplantation