Precision Alemtuzumab Dosing for Allogeneic Hematopoietic Cell Transplantation

Study Overview
=================
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 0.2-0.6 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 0.2-0.6 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.

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

Conditions
-----------------
Allogeneic Hematopoietic Cell Transplantation

Intervention / Treatment
-----------------
* Drug: Alemtuzumab


Participation Criteria
=================
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.

Ages Eligible for Study
-----------------
Minimum Age: 6 Weeks
Maximum Age: 30 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Alemtuzumab<br>Patients will be given 10 mg/m2 alemtuzumab divided over days -14, -13, and -12. The first dose should be limited to no more than 3 mg per the manufacturer's recommendation. If the calculated daily dose is greater than 3 mg, the first dose (day -14) should be limited to 3 mg and the remainder of the dosing should be divided over days -13 and -12. Alemtuzumab will be drawn into a sterile syringe and given to patients subcutaneously. | Drug: Alemtuzumab<br>* Alemtuzumab (Campath®) is a recombinant DNA-derived humanized monoclonal antibody directed against CD52. Alemtuzumab is produced in mammalian cell (Chinese hamster ovary) suspension culture in a medium containing neomycin. Neomycin is not detectable in the final product. Alemtuzumab is a sterile, clear, colorless, isotonic pH 6.8-7.4 solution for injection. Alemtuzumab is supplied in single-use clear glass ampules containing 30 mg of Alemtuzumab in 3 mL of solution. A single use vial of alemtuzumab contains 30 mg alemtuzumab, 8 mg sodium chloride, 1.44 mg dibasic sodium phosphate, 0.2 mg potassium chloride, 0.2 mg monobasic potassium phosphate, 0.1 mg polysorbate 80, and 0.0187 mg disodium edetate dihydrate.<br>* Other names: Campath;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Alemtuzumab levels | Number of patients who have alemtuzumab levels in the optimal therapeutic range on Day 0. | 100 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| CD4+ T cell count | CD4+ T cell count in patients who achieve the target window compared to patients who do not. | 100 days |