Backtracking Leukemia-Typical Somatic Mutations in Cord Blood

A comprehensive mechanistic and epidemiological study to obtain banked cord blood samples from consecutive childhood leukemia patients enrolled in the COG Project:EveryChild (APEC14B1) study. Will attempt to backtrack the initiating genomic alteration identified in the matched diagnostic leukemia sample and molecularly characterize pre-leukemic cells. The ultimate goal of this research is to pinpoint the cell of origin of leukemogenic alterations formed in utero, elucidating the etiology of these initiating mutations (as opposed to frank leukemia), and devising a test for circulating pre-leukemia that can be applied on a population-wide basis.

Study Overview

• Status: Recruiting
• Conditions: Acute Myeloid Leukemia; Acute Lymphoblastic Leukemia
• Intervention / Treatment: Other: Cord blood Sample Collection; Other: Case identification and recruitment; Other: Questionnaire Administration

Detailed Description

OBJECTIVES:

Primary Aim 1: To obtain stored cord blood and dried bloodspots of pediatric leukemia patients in Project:EveryChild.

Secondary Aim 2: To conduct preliminary backtracking and characterization of ALL- and AML-typical somatic mutations in cord blood and dried bloodspots.

OUTLINE:

Accrue patients with ALL and AML who indicate having banked cord blood at birth through the APEC14B1 intake questionnaire

• Study Type: Observational
• Enrollment (Estimated): 300

Contacts and Locations

• Study Contact: Name: Adam de Smith, PhD; Phone Number: (626) 218-4913; Email: adesmith@coh.org

Study Locations

• United States
  • Minnesota
    • Minneapolis, Minnesota, United States, 55455
      • Recruiting
      • University of Minnesota/Masonic Cancer Center
      • Contact: Logan Spector, PhD; Phone Number: 612-624-3912; Email: spector@umn.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 25 years (Child, Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Patients diagnosed with acute lymphoblastic leukemia (ALL) or acute myeloid leukemia (AML).

Description

Inclusion Criteria:

• The patient must have a diagnosis of acute lymphoblastic leukemia (ALL) or acute myeloid leukemia (AML).
• Stored diagnostic pre-treatment samples corresponding to the patient's original diagnosis of leukemia must be available for request from either the COG Biopathology Center or a treating institution
• The patient must be enrolled on APEC14B1 with consent to future contact and indicate that cord blood was stored at birth in the APEC14B1 registry intake data.
• The patient must also have been registered with COG by a North American (limited to the U.S. and Canada) member institution.
• ≤ 25 years old at the time of original diagnosis with ALL or AML
• The patient must be able to understand written and spoken English or Spanish
• All patients must provide their consent/assent, as appropriate, and for patients under the age of majority at least one parent or legal guardian must provide consent as well
• All institutional, FDA, and NCI requirements for human studies must be met

Exclusion Criteria:

• Patients who responded that cord blood was not stored at birth are excluded. Patients without stored diagnostic, pre-treatment leukemia samples at either the COG Biopathology Center or their treating institution are excluded.

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort

Intervention / Treatment

Ancillary-Correlative (Cord Blood collection); Accrue patients with ALL and AML who indicate having banked cord blood at birth through the COG Project:EveryChild (APEC14B1)

Other: Cord blood Sample Collection; Obtain banked cord blood samples from consecutive childhood leukemia patients; Other: Case identification and recruitment; Cases meeting eligibility and who have given consent through APEC14B1 for future contact for non-therapeutic studies; Other: Questionnaire Administration; The family will be given an option to complete questionnaire on paper, online, or over the telephone.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Prevalence of patient-specific somatic alterations found in cord blood in each molecularly-defined subtype of leukemia leukemia patients in Project:EveryChild.	Investigate less common cytogenetic subtypes for which the prenatal origins have not yet been investigated.	up to 5 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Density of alterations, calculated as # of alterations per # of cells assayed, within each flow-sorted cell population	Determine the prenatal origins across childhood leukemia subtypes, we will perform backtracking experiments using patient-specific ddPCR probes in matched tumor and CB samples from childhood ALL and AML patients in APEC14B1 with available stored CB. To identify the cells of origin of preleukemic alterations across childhood ALL and AML subtypes, we will perform single-cell sequencing analyses in flow-sorted CB cells from patients in which a prenatal lesion has been confirmed by backtracking.	Up to 5 years

Collaborators and Investigators

• Sponsor: Children's Oncology Group
• Collaborators: National Cancer Institute (NCI)
• Investigators: Study Chair: Logan Spector, PhD, University of Minnesota Masonic Cancer Center; Study Chair: Adam de Smith, PhD, Beckman Research Institute of the City of Hope

Study record dates

Study Major Dates

• Study Start (Actual): August 25, 2021
• Primary Completion (Estimated): September 30, 2026
• Study Completion (Estimated): September 30, 2026

Study Registration Dates

• First Submitted: August 13, 2021
• First Submitted That Met QC Criteria: August 13, 2021
• First Posted (Actual): August 20, 2021

Study Record Updates

• Last Update Posted (Actual): April 8, 2026
• Last Update Submitted That Met QC Criteria: April 2, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Immune System Diseases; Neoplasms by Histologic Type; Hematologic Diseases; Lymphatic Diseases; Lymphoproliferative Disorders; Immunoproliferative Disorders; Leukemia, Myeloid; Leukemia, Lymphoid; Leukemia; Hemic and Lymphatic Diseases; Leukemia, Myeloid, Acute; Precursor Cell Lymphoblastic Leukemia-Lymphoma
• Other Study ID Numbers: AEPI20N1

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No