Blood Samples to Identify Biomarkers in Patients Treated With Cyclophosphamide After Donor Stem Cell Transplant

Malignant Neoplasm Clinical Trial

Official title:

Blood Samples to Identify Biomarkers for Post-Transplant Cyclophosphamide

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04160390
• Other study ID #: 18358
• Secondary ID: NCI-2019-0737618
• Status: Recruiting
• Start date: November 13, 2018
• Est. completion date: April 24, 2027

Study information

• Verified date: March 2024
• Source: City of Hope Medical Center
• Contact: Jeannine McCune
• Phone: 626-359-8111
• Email: JMCCUNE[@]coh.org
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 60
• Est. completion date: April 24, 2027
• Est. primary completion date: April 24, 2027
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Allogeneic Hematopoietic Stem Cell Transplant Recipient
• Donor
• Malignant Neoplasm
• Neoplasms

Intervention

Other:
• Biospecimen Collection-Blood
Undergo collection of blood
• Biospecimen Collection-Stool
Undergo collection of stool

Locations

Country	Name	City	State
United States	City of Hope Medical Center	Duarte	California

Sponsors (2)

Lead Sponsor	Collaborator
City of Hope Medical Center	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Mathematical models of cyclophosphamide (CY) and mycophenolic acid pharmacokinetics (PK) with t cell effects.	Will determine whether readily available patient characteristics influence CY PK using population (pop)PK modeling. Will validate our existing popPK model of CY, 4HCY, and carboxyethylphosphoramide mustard.	Up to day 21
Secondary	Acute GVHD	Cumulative incidence estimates will be calculated with appropriate accounting for competing risks. Adjusted hazard ratios will be estimated via Cox regression models.	Up to 4 years