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

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).

Study Overview

• Status: Recruiting
• Conditions: Leukemia, Not Otherwise Specified; Leukemia, Other
• Intervention / Treatment: Drug: Cyclophosphamide; Other: Specimen collection

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.

• Study Type: Observational
• Enrollment (Estimated): 120

Contacts and Locations

• Study Contact: Name: Elizabeth Parke; Phone Number: 980-442-2011; Email: elizabeth.parke@atriumhealth.org

Study Locations

• United States
  • North Carolina
    • Charlotte, North Carolina, United States, 28204
      • Recruiting
      • Levine Cancer Institute
      • Contact: Elizabeth Parke; Phone Number: 980-442-2011; Email: elizabeth.parke@atriumhealth.org

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study 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.

Description

Inclusion Criteria

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

1. Informed consent and HIPAA authorization for release of personal health information signed by the subject.
2. Age ≥ 18 years at the time of consent.
3. 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.
4. Recipient only: Planned post-transplant cyclophosphamide
5. 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:

1. 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.
2. Recipient only: Treatment with any investigational drug within 30 days prior to day -6 of treatment
3. 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.

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Recipient; Cyclophosphamide	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.
Donor; Specimen collection	Other: Specimen collection; Buccal swabs will be obtained from donors for pharmacogenomics.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	Approx. 24 mos

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of chronic GVHD	Calculated for each subject as a binary variable indicating whether or not subject experienced chronic GVHD	Approx. 24 mos
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.	Approx. 10 days
Toxicities	The incidence of adverse events of special interests will be collected according to CTCAE version 4.03	Approx. 180 days
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.	Approx. 24 mos

Collaborators and Investigators

• Sponsor: Wake Forest University Health Sciences
• Collaborators: Atrium Health Levine Cancer Institute
• Investigators: Principal Investigator: Aleksander Chojecki, MD, Wake Forest University Health Sciences

Study record dates

Study Major Dates

• Study Start (Actual): July 13, 2018
• Primary Completion (Estimated): October 1, 2033
• Study Completion (Estimated): August 1, 2035

Study Registration Dates

• First Submitted: May 2, 2018
• First Submitted That Met QC Criteria: June 1, 2018
• First Posted (Actual): June 14, 2018

Study Record Updates

• Last Update Posted (Actual): July 13, 2026
• Last Update Submitted That Met QC Criteria: July 10, 2026
• Last Verified: July 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Neoplasms by Histologic Type; Hematologic Diseases; Hemic and Lymphatic Diseases; Leukemia; Organic Chemicals; Investigative Techniques; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Hydrocarbons; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Phosphoramides; Organophosphorus Compounds; Cyclophosphamide; Specimen Handling
• Other Study ID Numbers: IRB00081375; LCI-HEM-HCT-PTCY-001 (Other Identifier: Atrium Health); Pro00024582 (Other Identifier: Advarra IRB); NCI-2024-06503 (Other Identifier: National Cancer Institute)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No