Study of Thiotepa and TEPA Drug Exposure in Pediatric Hematopoietic Stem Cell Transplant Patients

NCT03609840 | Completed FDA Drug

• 2 other identifiers: 17-2199417087
• Study Type: observational
• Target: 25
• Locations: 1 country
• Sites: 1

Brief Summary

Thiotepa is a chemotherapy drug used extensively in bone marrow transplantation. Thiotepa is a prodrug that undergoes metabolic conversion in the liver by CYP2B6 and CYP3A4 to its primary active metabolite, triethylene phosphoramide (TEPA). The goal of this study is to determine what causes some children to have different drug concentrations of thiotepa and TEPA in their bodies and if drug levels are related to whether or not a child experiences severe side-effects during their bone marrow transplant. The hypothesis is that certain clinical and genetic factors cause changes in thiotepa and TEPA drug levels in pediatric bone marrow transplant patients and that high levels may cause severe side-effects.

Conditions

Hematologic Malignancies; Nonmalignant Diseases; Immune Deficiency; Hemoglobinopathies; Genetic Inborn Errors of Metabolism; Fanconi Anemia; Thalassemia; Sickle Cell Disease

Keywords

Thiotepa; TEPA; Pediatric; Hematopoietic; Transplant

Outcome Measures

Primary Outcomes (4)

• Analysis of the Area under the Plasma Concentration versus Time Curve (AUC) of thiotepa for HCT in pediatric patients.

  Area-under-the-curve (AUC) will be derived from the empirical Bayes estimates of individual clearance

  2 hours post start of infusion

• Analysis of the Area under the Plasma Concentration versus Time Curve (AUC) of thiotepa for HCT in pediatric patients.

  Area-under-the-curve (AUC) will be derived from the empirical Bayes estimates of individual clearance

  4 hours post start of infusion

• Analysis of the Area under the Plasma Concentration versus Time Curve (AUC) of thiotepa for HCT in pediatric patients.

  Area-under-the-curve (AUC) will be derived from the empirical Bayes estimates of individual clearance

  6 hours post start of infusion

• Analysis of the Area under the Plasma Concentration versus Time Curve (AUC) of thiotepa for HCT in pediatric patients.

  Area-under-the-curve (AUC) will be derived from the empirical Bayes estimates of individual clearance

  24 hours post start of infusion

Secondary Outcomes (3)

• Event free survival according to the AUC of thiotepa

  1 month post transplant

• Event free survival according to the AUC of thiotepa

  3 months post transplant

• Event free survival according to the AUC of thiotepa

  1 year post transplant

Study Arms (1)

Pediatric Hematopoietic Stem Cell Transplant Recipients

Children undergoing hematopoietic stem cell transplant (HCT) at University of California, San Francisco Benioff Children's Hospital

Drug: Thiotepa

Interventions

Thiotepa DRUG

Given IV

Also known as: Alkylating antineoplastic agent, Tepadina

Pediatric Hematopoietic Stem Cell Transplant Recipients

Eligibility Criteria

• Age: Up to 17 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)
• Sampling Method: Non-Probability Sample

Study Population

The target population for the proposed study includes children 0-17 years of age undergoing autologous and allogeneic HCT for the treatment of malignant and nonmalignant disorders. Patients receiving thiotepa over 3 to 5 days are eligible to participate. All patients enrolled in this study will undergo PK sampling on the inpatient pediatric BMT unit at UCSF Benioff Children's Hospital. The proposed research will not study any patients receiving thiotepa in a clinic or any other out-patient setting.

You may qualify if:

• be between 0 to 17 years of age;
• meet protocol specific eligibility criteria for autologous or allogeneic HCT
• will be receiving thiotepa as part of their conditioning regimen.

You may not qualify if:

• Any child 7-17 years of age unwilling to provide assent
• Parent or guardian unwilling to provide written consent

Sponsors & Collaborators

• University of California, San Francisco: lead

Study Sites (1)

University of California, San Francisco

San Francisco, California, 94143, United States

Location

Biospecimen

Retention: SAMPLES WITH DNA

Plasma

MeSH Terms

Conditions

Hematologic Neoplasms; Immunologic Deficiency Syndromes; Hemoglobinopathies; Fanconi Anemia; Thalassemia; Anemia, Sickle Cell

Interventions

Thiotepa

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Immune System Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Anemia, Hypoplastic, Congenital; Anemia, Aplastic; Anemia; Congenital Bone Marrow Failure Syndromes; Bone Marrow Failure Disorders; Bone Marrow Diseases; DNA Repair-Deficiency Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Anemia, Hemolytic, Congenital; Anemia, Hemolytic

Intervention Hierarchy (Ancestors)

Phosphoramides; Organophosphorus Compounds; Organic Chemicals; Triethylenephosphoramide; Aziridines; Azirines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Janel Long-Boyle, PharmD, PhD

  University of California, San Francisco

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: OTHER
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 5, 2018
• First Posted: August 1, 2018
• Study Start: May 24, 2017
• Primary Completion: July 31, 2023
• Study Completion: July 31, 2023
• Last Updated: September 21, 2023

Record last verified: 2023-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)