Precision Dosing of Alemtuzumab

Sponsor

Children's Hospital Medical Center, Cincinnati (Other)

Overall Status

Completed

CT.gov ID

NCT03302754

Collaborator

(none)

Enrollment

Location

Arm

17.1

Actual Duration (Months)

0.7

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The purpose of this study is to conduct a pilot trial of a Precision Dosing approach to alemtuzumab dosing for allogeneic hematopoietic cell transplantation of patients with non-malignant diseases. The investigators will measure the ability to use a population PK model of alemtuzumab to target patient Day 0 alemtuzumab levels to 0.15-0.6ug/mL in a pilot study of 20 patients.

Condition or Disease	Intervention/Treatment	Phase
Allogeneic Hematopoietic Cell Transplantation	Drug: Alemtuzumab	N/A

Detailed Description

The hypothesis is that the model-informed dosing regimen will prospectively allow the precision dosing of alemtuzumab to target Day 0 levels to fall between 0.15-0.6ug/mL in greater than 80% of patients. The investigators have chosen a conservative pilot study approach, and the aim is to achieve Day 0 alemtuzumab levels between 0.15-0.6ug/mL in greater than 60% of 20 patients enrolled in this pilot study based on a Simon two-stage design as detailed below.

A Simon two-stage design (Simon, 1989) is being used. The null hypothesis that 30% of patients will achieve a Day 0 alemtuzumab level between 0.15-0.6ug/mL will be tested against a one-sided alternative that the alemtuzumab dose modification will result in 60% of patients achieving a Day 0 alemtuzumab level between 0.15-0.6ug/mL. In the first stage, 7 patients will be accrued. If there are 2 or fewer patients that achieve Day 0 alemtuzumab levels within the range of 0.15-0.6ug/mL, the study will be stopped. Otherwise, 13 additional patients will be accrued for a total of 20. The null hypothesis will be rejected if 11 or more patients achieve a Day 0 level of 0.15-0.6ug/mL within the total 20 patients. This design yields a type I error rate of 0.04 and power of 0.82 when the true response rate is 0.60. The investigators will enroll up to 30 patients in order allow for subject withdrawal, but will stop enrollment once 20 patients reach Day 0.

Study Design

Study Type:

Interventional

Actual Enrollment :

12 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Other

Official Title:

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

Actual Study Start Date :

Oct 5, 2017

Actual Primary Completion Date :

Mar 10, 2019

Actual Study Completion Date :

Mar 10, 2019

Arms and Interventions

Arm	Intervention/Treatment
Other: Alemtuzumab Patients less than 15kg will be given 0.6mg/kg alemtuzumab divided over days -14, -13, and -12 (0.2mg/kg/dose). Patients greater than 15kg will be given a 3mg "test" dose on day -14 in order to limit the first dose to no more than 3 mg per the manufacturer's recommendation. This will be followed by 0.23mg/kg/dose on days -13 and -12 (to equal a total dose of approximately 0.5-0.6mg/kg). Alemtuzumab will be drawn into a sterile syringe and given to patients subcutaneously.	Drug: Alemtuzumab 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. 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. Other Names: Campath

Arm

Intervention/Treatment

Other: Alemtuzumab

Patients less than 15kg will be given 0.6mg/kg alemtuzumab divided over days -14, -13, and -12 (0.2mg/kg/dose). Patients greater than 15kg will be given a 3mg "test" dose on day -14 in order to limit the first dose to no more than 3 mg per the manufacturer's recommendation. This will be followed by 0.23mg/kg/dose on days -13 and -12 (to equal a total dose of approximately 0.5-0.6mg/kg). Alemtuzumab will be drawn into a sterile syringe and given to patients subcutaneously.

Drug: Alemtuzumab

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. 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.

Other Names:

Campath

Outcome Measures

Primary Outcome Measures

Percentage of patients who have alemtuzumab levels in the optimal therapeutic range on Day 0. [100 Days]

Eligibility Criteria

Criteria

Ages Eligible for Study:

6 Weeks to 30 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Patients who are undergoing RIC HCT with alemtuzumab, fludarabine, and melphalan at CCHMC for treatment of a non-malignant disease.
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 PI and medical monitor.

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 2 weeks.
Patients receiving dialysis.
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 such as epidermolysis bullosa).

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Cincinnati Children's Hospital Medical Center	Cincinnati	Ohio	United States	45229

Sponsors and Collaborators

Children's Hospital Medical Center, Cincinnati

Investigators

Principal Investigator: Rebecca Marsh, MD, Children's Hospital Medical Center, Cincinnati

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

Children's Hospital Medical Center, Cincinnati

ClinicalTrials.gov Identifier:

NCT03302754

Other Study ID Numbers:

2017-2206

First Posted:

Oct 5, 2017

Last Update Posted:

Oct 4, 2019

Last Verified:

Sep 1, 2019

Individual Participant Data (IPD) Sharing Statement:

Plan to Share IPD:

Studies a U.S. FDA-regulated Drug Product:

Studies a U.S. FDA-regulated Device Product:

Product Manufactured in and Exported from the U.S.:

Additional relevant MeSH terms:

Alemtuzumab

Study Results

No Results Posted as of Oct 4, 2019