Factors Affecting Post-transplant Cyclophosphamide (PTCy) Efficacy

Wake Forest University (WFU)

Status

Enrolling

Conditions

Leukemia, Not Otherwise Specified

Leukemia, Other

Treatments

Other: Specimen collection

Drug: Cyclophosphamide

Study type

Observational

Funder types

Other

Identifiers

NCT03555851

NCI-2024-06503 (Other Identifier)

Pro00024582 (Other Identifier)

LCI-HEM-HCT-PTCY-001

IRB00081375

Details and patient eligibility

About

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).

Full 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.

Enrollment

120 estimated patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

Inclusion and exclusion criteria

Inclusion Criteria

Recipients and donors must meet all of the following applicable inclusion criteria to participate in this study:

Informed consent and HIPAA authorization for release of personal health information signed by the subject.
Age ≥ 18 years at the time of consent.
Subject is scheduled as a recipient or respective donor (Donor consent/participation is not required for subjects undergoing matched unrelated donor HCT) for the following hematopoietic stem cell transplants (HCT) procedures using a non-myeloablative regimen at Levine Cancer Institute (LCI), and has been deemed a qualified candidate by his/her physician, per LCI medical standards: haplo-identical donor HCT, match related donor (MRD) HCT, matched unrelated donor (MUD) HCT.
Recipient only: Planned post-transplant cyclophosphamide
As determined by the enrolling physician, ability of the subject to understand and comply with study procedures for the entire length of the study

Exclusion Criteria

Subjects meeting any of the criteria below may not participate in the study:

Recipient only (applies only to haplo-identical and MRD HCT recipients; not required for MUD HCT recipients): Does not have a respective donor who is willing to sign informed consent for participation in this study.
Recipient only: Treatment with any investigational drug within 30 days prior to day -6 of treatment
Donor only (applies only to haplo-identical and MRD HCTs; donor participation is not required for MUD HCTs): Does not have a respective recipient who is willing to sign informed consent for participation in this study.