Clinical trial NCT03555851: Factors Affecting Post-transplant Cyclophosphamide (PTCy) Efficacy
Official title: 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
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Leukemia, Not Otherwise Specified
Leukemia, Other
Lead sponsor: Wake Forest University Health Sciences
Sponsor class: OTHER
Collaborators: name: Atrium Health Levine Cancer Institute
First posted: 2018-06-14
Enrollment: 120
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Comparison of Cy cMax Values
timeFrame: Approx. 24 mos
Secondary outcomes:
measure: Incidence of chronic GVHD
timeFrame: Approx. 24 mos
measure: Cy exposure
timeFrame: Approx. 10 days
measure: Toxicities
timeFrame: Approx. 180 days
measure: Pharmacogenetics of Cy-related genes
timeFrame: Approx. 24 mos
Other outcomes:
Locations:
city: Charlotte
country: United States
facility: Levine Cancer Institute
state: North Carolina
Study officials:
affiliation: Wake Forest University Health Sciences
name: Aleksander Chojecki, MD
role: PRINCIPAL_INVESTIGATOR
References: