Factors Affecting Post-transplant Cyclophosphamide (PTCy) Efficacy

Recruiting

Brief 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.

Recruitment & Eligibility

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Arm && Interventions

Primary Outcome Measures

Name	Time	Method
Comparison of Cy cMax Values	Approx. 24 mos	Evaluation and comparison of average Day 3 Cy cMax values between subjects who experience acute GVHD versus subjects who do not experience acute GVHD

Secondary Outcome Measures

Name	Time	Method
Pharmacogenetics of Cy-related genes	Approx. 24 mos	Evaluation of the prognostic value of pharmacogenetics (PG) of Cy-related candidate genes from the recipient's germ-line DNA, using logistic regression, on the incidence and severity of acute and chronic GVHD. PG of Cy-related candidate genes will be performed on 12 genes. Genes encoding CYP enzymes will be classified into metabolizer status and other genes will be classified as either wild type, heterozygous, or homozygous variants.
Incidence of chronic GVHD	Approx. 24 mos	Calculated for each subject as a binary variable indicating whether or not subject experienced chronic GVHD
Cy exposure	Approx. 10 days	Cy (and related metabolites) exposure will be calculated using area under the concentration curve (AUC). This will be accomplished using the trapezoidal approximation, and will be calculated over the 24 hour period following first pre-transplant dose of Cy and over the 24 hour period following post-transplant dose of Cy.
Toxicities	Approx. 180 days	The incidence of adverse events of special interests will be collected according to CTCAE version 4.03

Locations (1): Levine Cancer Institute
🇺🇸
Charlotte, North Carolina, United States