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

Recruiting

• Conditions: Allogeneic Hematopoietic Stem Cell Transplant Recipient; Malignant Neoplasm; Donor
• Interventions: Other: Biospecimen Collection-Blood; Other: Biospecimen Collection-Stool

• Registration Number: NCT04160390
• Lead Sponsor: City of Hope Medical Center

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.

Study Timeline

• Study Start: 2018-11-13
• Study First Submitted: 2019-11-08
• Study First Submitted QC: 2019-11-08
• Study First Posted: 2019-11-13
• Status Verified: 2025-03
• Last Update Submitted: 2025-03-06
• Last Update Posted: 2025-03-07
• Primary Completion: 2027-04-24
• Study Completion: 2027-04-24

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 60

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

Exclusion Criteria

Not provided

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Arm I (biospecimen collection)	Biospecimen Collection-Blood	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.
Arm I (biospecimen collection)	Biospecimen Collection-Stool	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.

Primary Outcome Measures

Name	Time	Method
Mathematical models of cyclophosphamide (CY) and mycophenolic acid pharmacokinetics (PK) with t cell effects.	Up to day 21	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.

Secondary Outcome Measures

Name	Time	Method
Acute GVHD	Up to 4 years	Cumulative incidence estimates will be calculated with appropriate accounting for competing risks. Adjusted hazard ratios will be estimated via Cox regression models.

Trial Locations

Locations (1)

City of Hope Medical Center; 🇺🇸 Duarte, California, United States