Clinical trial NCT04160390: Blood Samples to Identify Biomarkers in Patients Treated With Cyclophosphamide After Donor Stem Cell Transplant
Official title: Blood Samples to Identify Biomarkers for Post-Transplant Cyclophosphamide
Study type: OBSERVATIONAL
Overall status: SUSPENDED
Conditions: Allogeneic Hematopoietic Stem Cell Transplant Recipient
Donor
Malignant Neoplasm
Lead sponsor: City of Hope Medical Center
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2019-11-13
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients of the City of Hope Comprehensive Cancer Center and donors.

Brief summary: This trial uses blood samples to understand how patients' bodies process and respond to a drug called cyclophosphamide given after a donor stem cell transplant. Identifying biomarkers (molecules that can indicate normal or abnormal processes) may help researchers develop a blood test that can be used to predict how well patients will process and respond to cyclophosphamide.

Detailed description: "Ancillary-Correlative" study type

PRIMARY OBJECTIVES:

I. To determine whether endogenous metabolomics compounds obtained before cyclophosphamide administration can predict the ratio of 4hydroxycyclophosphamide to cyclophosphamide area under the curve (4HCY/CY AUC).

II. To evaluate mathematic models of CY and mycophenolic acid (MPA) pharmacokinetics and develop mathematic models including these pharmacokinetics, -omics data and clinical outcomes.

SECONDARY OBJECTIVES:

I. To assess if recipients' metabolomics and pharmacokinetics (e.g., CY and its metabolites AUCs) are associated with acute graft versus host disease (GVHD) and other clinical outcomes.

II. To assess the association of the intestinal microbiome with the plasma metabolome, acute GVHD and other clinical outcomes.

III. To obtain donor blood samples at one time pre-transplant and assess if donors' metabolomics are associated with acute GVHD and other clinical outcomes.

EXPLORATORY OBJECTIVE:

I. Donor and recipient germline deoxyribonucleic acid (DNA) isolation and genomic analysis.

OUTLINE: Participants are assigned to 1 of 2 arms.

ARM I (PATIENTS RECEIVING A HAPLOIDENTICAL TRANSPLANT): Patients undergo collection of blood prior to transplant, on day 0, days 3-7, day 14, and day 21. Patients also undergo collection of saliva prior to transplant and collection of stool prior to and post-transplant. Donors undergo collection of blood and saliva within 8 weeks prior to donation.

Eligibility criteria: Inclusion Criteria:

* Scheduled to undergo allogeneic hematopoietic cell transplant (HCT) with a haploidentical donor.
* Allogeneic HCT scheduled to treat any underlying disease. Patients with nonmalignant diseases or cancer are eligible
* Scheduled to receive post-transplant cyclophosphamide (any dose, any number of doses, any dosing frequency) as part of their post-graft immunosuppression or GVHD prophylaxis. Patients enrolled on treatment protocols that include post transplant cyclophosphamide (PTCy) but do not include mycophenolate mofetil (MMF) or tacrolimus can participate
* Willingness to:

  * Provide blood
  * Permit medical record review

Primary outcomes:
measure: Mathematical models of cyclophosphamide (CY) and mycophenolic acid pharmacokinetics (PK) with t cell effects.
timeFrame: Up to day 21
Secondary outcomes:
measure: Acute GVHD
timeFrame: Up to 4 years
Other outcomes:
Locations:
city: Duarte
country: United States
facility: City of Hope Medical Center
state: California
Study officials:
affiliation: City of Hope Medical Center
name: Jeannine S McCune
role: PRINCIPAL_INVESTIGATOR
References: