Clinical trial NCT05501756: Precision Alemtuzumab Dosing for Allogeneic Hematopoietic Cell Transplantation
Official title: Precision Alemtuzumab Dosing for Allogeneic Hematopoietic Cell Transplantation in Non-Malignant Diseases
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Allogeneic Hematopoietic Cell Transplantation
Lead sponsor: Children's Hospital Medical Center, Cincinnati
Sponsor class: OTHER
First posted: 2022-08-15
Enrollment: 60
Sex: ALL
Minimum age (years): 6
Maximum age (years): 30
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: Alemtuzumab is an antibody that reduces the strength of the immune system that is given in preparation for allogeneic hematopoietic cell transplant (HCT). In this research study the investigators want to find out if they can adjust the dose of alemtuzumab used as part of allogeneic HCT to target the level of Day 0 (the planned day of graft infusion) to an optimal therapeutic window of 0.15-0.9 ug/mL.

Detailed description: Alemtuzumab levels at Day 0 can affect:

* the chances of developing acute graft versus host disease (GVHD), which is an immune reaction of the donor cells against your own tissues
* the chances of developing mixed chimerism, which is having a mixture of your own cells and donor cells after HCT, and
* recovery of your immune system following transplant.

High levels of alemtuzumab are associated with more mixed chimerism and slower immune recovery, while low levels are associated with more acute GVHD. The investigators have developed a plan to adjust the alemtuzumab dose for patients to target Day 0 levels to fall within an ideal effective range of 0.15-0.9 ug/mL. This range may minimize the risks of these complications. The investigators are conducting this study to determine if the current plan for alemtuzumab dosing will be successful in the majority of patients and evaluate the impact on the clinical outcomes of acute GVHD, mixed chimerism, and immune recovery.

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.
* Age ≥ 6 weeks to ≤ 30 years (at time of enrollment).
* 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.

Primary outcomes:
measure: Alemtuzumab levels
timeFrame: 100 days
Secondary outcomes:
measure: CD4+ T cell count
timeFrame: 100 days
Other outcomes:
Locations:
city: Cincinnati
country: United States
facility: Cincinnati Children's Hospital Medical Center
state: Ohio
Study officials:
affiliation: Children's Hospital Medical Center, Cincinnati
name: Parinda Mehta, MD
role: PRINCIPAL_INVESTIGATOR
References: