NCT03555851

Factors Affecting Post-transplant Cyclophosphamide (PTCy) Efficacy

Elucidation of Factors Predicting Efficacy and Toxicity of Post Transplantation Cyclophosphamide (PTCy) as a Strategy for Graft Versus Host Disease Prevention in Haploidentical, Matched Related Donor and Matched Unrelated Donor Peripheral Blood Hematopoietic Cell Transplantation

• Status: Recruiting
• Phase: —
• Study type: Observational
• Enrollment: 120 (estimated)
• Sponsor: Wake Forest University Health Sciences · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This study will examine the influence of donor and recipient pharmacogenetics (PG), drug pharmacokinetics (PK), and T cell phenotypes and how it may permit a tailored dosing strategy to improve the therapeutic index of post-transplant cyclophosphamide (PTCy) and optimize the graft versus tumor effect, while minimizing acute and chronic graft versus host disease (GVHD).

Detailed description

The primary objective of this single-arm, pilot study is to determine whether pharmacogenetics (PG) of Cy-related candidate genes from the recipients and/or donors (haploidentical and matched related donor HCTs only) germ-line DNA is associated with incidence and severity of acute and chronic GVHD. Secondary objectives include determining whether pharmacogenetics (PG) of Cy-related candidate genes from the recipients and/or donors (haploidentical and matched related donor HCTs only) germ-line DNA is associated with Cy (and metabolites) exposure and toxicities; quantifying Cy (and related metabolites) exposure measured as the area under the concentration time curve (AUC) from zero to 24 hours both before (day -6) and after transplant (day +3), and correlate exposure with incidence of acute and chronic GVHD, and Adverse Events of Special Interest (AESIs); and determining whether immune activation or polarization prior to or following Cy GVHD prophylaxis is associated with grade of acute or chronic GVHD grade and AESIs. Safety objects include evaluating Cy administered, adverse events of special interest (including deaths while on study therapy), selected laboratory parameters (including time to neutrophil recovery), and immunosuppressant concomitant medications administration. Initially, 20 participants (HCT recipients and their respective haploidentical or matched related donors) will be enrolled with a subsequent 100 additional subjects enrolled.

Conditions

• Leukemia, Not Otherwise Specified
• Leukemia, Other

Interventions

Type	Name	Description
DRUG	Cyclophosphamide	Pharmacogenomics of candidate genes and pharmacokinetic analyses of cyclophosphamide administered as part of a reduced intensity conditioning (RIC) regimen and as post-transplant GVHD prophylaxis will be examined.
OTHER	Specimen collection	Buccal swabs will be obtained from donors for pharmacogenomics.

Timeline

• Start date: 2018-07-13
• Primary completion: 2033-10-01
• Completion: 2035-08-01
• First posted: 2018-06-14
• Last updated: 2026-01-08

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study