Health TrialsbyHealthPanel

Factors Affecting Post-transplant Cyclophosphamide (PTCy) Efficacy

ConditionsLeukemia, Not Otherwise SpecifiedLeukemia, Other
Trial statusRecruiting
Trial phaseNot listed
Trial typeObservational
Biological sexAll
Age18+
SponsorWake Forest University Health Sciences

About this trial

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).

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

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

Disqualifiers

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.

Trial population

Subjects who are scheduled as a recipient or respective donor for the following hematopoietic stem cell transplants (HCT): haplo-identical donor HCT, match related donor (MRD) HCT, matched unrelated donor (MUD) HCT.

Trial design

Design model

Cohort

Time perspective

Prospective

Treatments tested in this trial

  • Cyclophosphamide

    Drug

    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.

  • Specimen collection

    Other intervention

    Buccal swabs will be obtained from donors for pharmacogenomics.

Treatment groups

120 Participants
are divided into 2 treatment groups
Group A: Recipient2 interventions
Group B: Donor1 intervention

Trial outcomes

Primary outcomes

1

Comparison of Cy cMax Values

Evaluation and comparison of average Day 3 Cy cMax values between subjects who experience acute GVHD versus subjects who do not experience acute GVHD

Time frame
Approx. 24 mos

Secondary outcomes

1

Incidence of chronic GVHD

Calculated for each subject as a binary variable indicating whether or not subject experienced chronic GVHD

Time frame
Approx. 24 mos
2

Cy exposure

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.

Time frame
Approx. 10 days
3

Toxicities

The incidence of adverse events of special interests will be collected according to CTCAE version 4.03

Time frame
Approx. 180 days
4

Pharmacogenetics of Cy-related genes

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.

Time frame
Approx. 24 mos

Other outcomes

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

Wake Forest University Health Sciences

Lead sponsor

Atrium Health Levine Cancer Institute

Collaborator

Source ClinicalTrials.gov
Apply now