Precision Alemtuzumab Dosing for Allogeneic Hematopoietic Cell Transplantation

Sponsor
Children's Hospital Medical Center, Cincinnati (Other)
Overall Status
Not yet recruiting
CT.gov ID
NCT05501756
Collaborator
(none)
60
1
64

Study Details

Study Description

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.

Condition or Disease Intervention/Treatment Phase
Phase 2

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.

Study Design

Study Type:
Interventional
Anticipated Enrollment :
60 participants
Allocation:
N/A
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
Precision Alemtuzumab Dosing for Allogeneic Hematopoietic Cell Transplantation in Non-Malignant Diseases
Anticipated Study Start Date :
Sep 1, 2022
Anticipated Primary Completion Date :
Sep 1, 2027
Anticipated Study Completion Date :
Jan 1, 2028

Arms and Interventions

Arm Intervention/Treatment
Experimental: Alemtuzumab

Patients less than 0.3m2 will be given 10 mg/m2 alemtuzumab divided over days -14, -13, and -12 (approximately 3.33mg/m2/day) prior to transplant. Patients greater than 0.3m2 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 the remainder of the dose divided on days -13 and -12 (to equal a total dose of approximately 10mg/m2) prior to transplant. 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. 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.
Other Names:
  • Campath
  • Outcome Measures

    Primary Outcome Measures

    1. Alemtuzumab levels [100 days]

      Number of patients who have alemtuzumab levels in the optimal therapeutic range on Day 0.

    Secondary Outcome Measures

    1. CD4+ T cell count [100 days]

      CD4+ T cell count in patients who achieve the target window compared to patients who do not.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    6 Weeks to 30 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    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.

    Contacts and Locations

    Locations

    No locations specified.

    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:
    NCT05501756
    Other Study ID Numbers:
    • 2022-0447
    First Posted:
    Aug 15, 2022
    Last Update Posted:
    Aug 15, 2022
    Last Verified:
    Aug 1, 2022
    Individual Participant Data (IPD) Sharing Statement:
    No
    Plan to Share IPD:
    No
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Product Manufactured in and Exported from the U.S.:
    No
    Additional relevant MeSH terms:

    Study Results

    No Results Posted as of Aug 15, 2022