Diagnostic Testing for Pediatric Leukemia
Recruiting in Palo Alto (17 mi)
+178 other locations
Overseen byMichele S Redell
Age: < 65
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 1 & 2
Recruiting
Sponsor: LLS PedAL Initiative, LLC
Disqualifiers: Over 22 years, others
No Placebo Group
Trial Summary
What is the purpose of this trial?This study aims to use clinical and biological characteristics of acute leukemias to screen for patient eligibility for available pediatric leukemia sub-trials. Testing bone marrow and blood from patients with leukemia that has come back after treatment or is difficult to treat may provide information about the patient's leukemia that is important when deciding how to best treat it, and may help doctors find better ways to diagnose and treat leukemia in children, adolescents, and young adults.
Do I need to stop my current medications for this trial?
The trial information does not specify whether you need to stop taking your current medications.
What data supports the effectiveness of the treatment Biospecimen Collection for pediatric leukemia?
Research shows that using blood-derived liquid biopsies can help identify specific genetic changes in children's tumors, which can guide treatment decisions. This approach has been successful in identifying targetable mutations in pediatric patients with high-risk solid tumors, suggesting it could be useful for leukemia as well.
12345Is blood-derived liquid biopsy safe for children with cancer?
The study on blood-derived liquid biopsy (LB) for children with high-risk cancers did not report any safety issues, suggesting it is generally safe for use in pediatric patients.
16789How does the Biospecimen Collection treatment for pediatric leukemia differ from other treatments?
Biospecimen Collection is unique because it involves collecting samples like blood or tissue to better understand the genetic makeup of leukemia, rather than directly treating the disease. This approach can help identify specific genetic changes in leukemia, which may guide more personalized treatment strategies in the future.
49101112Eligibility Criteria
This trial is for children, adolescents, and young adults under 22 with leukemia that's come back or is hard to treat. They must have consent from parents/guardians if needed, meet FDA and NCI human study requirements, and have specific types of acute myeloid leukemia (AML), myelodysplastic syndrome (MDS), mixed phenotype acute leukemia (MPAL), juvenile myelomonocytic leukemia (JMML), or relapsed ALL.Inclusion Criteria
This criterion means that the patient needs to meet certain conditions, but the specific conditions are not provided.
I am under 22 years old.
My leukemia linked to Down syndrome has returned or is not responding to treatment.
+8 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
1 visit (in-person)
Biospecimen Collection
Patients undergo collection of blood and/or bone marrow samples at baseline, end of treatment cycle(s), and at relapse/refractory disease status (if applicable)
Varies
Follow-up
Participants are monitored every 3 months for 2 years, and then every 6 months for 3 years after completion of the study
5 years
Participant Groups
The trial involves collecting bone marrow and blood samples from patients to understand the clinical and biological characteristics of their acute leukemias. This information may help determine eligibility for other sub-trials aimed at finding better ways to diagnose and treat pediatric leukemia.
1Treatment groups
Experimental Treatment
Group I: Screening (biospecimen collection)Experimental Treatment1 Intervention
Patients undergo collection of blood and/or bone marrow samples at baseline, end of treatment cycle(s), and at relapse/refractory disease status (if applicable).
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
MedStar Georgetown University HospitalWashington, United States
Corewell Health Grand Rapids Hospitals - Helen DeVos Children's HospitalGrand Rapids, MI
Corewell Health Children'sRoyal Oak, MI
University of Missouri Children's HospitalColumbia, MO
More Trial Locations
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Who Is Running the Clinical Trial?
LLS PedAL Initiative, LLCLead Sponsor
National Cancer Institute (NCI)Collaborator
Children's Oncology GroupCollaborator
References
Blood-Derived Liquid Biopsies Using Foundation One® Liquid CDx for Children and Adolescents with High-Risk Malignancies: A Monocentric Experience. [2022]Precision oncology requires tumor molecular profiling to identify actionable targets. Tumor biopsies are considered as the gold standard, but their indications are limited by the burden of procedures in children. Blood-derived liquid biopsy (LB) is a potential alternative that is not yet documented in real-world settings, especially in pediatric oncology. We performed a retrospective analysis of children and teenagers with a relapsing or refractory disease, upon whom LB was performed using the Foundation One® liquid CDx from 1 January 2020 to 31 December 2021 in a single center. Forty-five patients (27 boys) were included, with a median age of 9 years of age (range: 1.5-17 years old). Underlying malignancies were neuroblastoma (12 patients), bone sarcoma (12), soft tissue sarcoma (9), brain tumors (7), and miscellaneous tumors (5). Forty-three patients had metastatic disease. Six patients had more than one biopsy because of a failure in first LB. Median time to obtain results was 13 days. Overall, analysis was successful for 33/45 patients. Eight patients did not present any molecular abnormalities. Molecular alterations were identified in 25 samples with a mean of 2.1 alterations per sample. The most common alterations concerned TP53 (7 pts), EWS-FLI1 (5), ALK (3), MYC (3), and CREBBP (2). TMB was low in all cases. Six patients received treatment based on the results from LB analysis and all were treated off-trial. Three additional patients were included in early phase clinical trials. Mean duration of treatment was 85 days, with one patient with stable disease after eight months. Molecular profiling using Foundation One® Liquid CDx was feasible in pediatric patients with high-risk solid tumors and lead to identification of targetable mutations in a subset of patients.
Assessment of circulating tumor DNA in pediatric solid tumors: The promise of liquid biopsies. [2020]Circulating tumor DNA can be detected in the blood and body fluids of patients using ultrasensitive technologies, which have the potential to improve cancer diagnosis, risk stratification, noninvasive tumor profiling, and tracking of treatment response and disease recurrence. As we begin to apply "liquid biopsy" strategies in children with cancer, it is important to tailor our efforts to the unique genomic features of these tumors and address the technical and logistical challenges of integrating biomarker testing. This article reviews the literature demonstrating the feasibility of applying liquid biopsy to pediatric solid malignancies and suggests new directions for future studies.
The Norwegian childhood cancer biobank. [2022]The rapidly expanding era of "omics" research is highly dependent on the availability of quality-proven biological material, especially for rare conditions such as pediatric malignancies. Professional biobanks provide such material, focusing on standardized collection and handling procedures, distinctive quality measurements, traceability of storage conditions, and accessibility. For pediatric malignancies, traditional tumor biobanking is challenging due to the rareness and limited amount of tissue and blood samples. The higher molecular heterogeneity, lower mutation rates, and unique genomic landscapes, however, renders biobanking of this tissue even more crucial.
OncoKids: A Comprehensive Next-Generation Sequencing Panel for Pediatric Malignancies. [2019]The OncoKids panel is an amplification-based next-generation sequencing assay designed to detect diagnostic, prognostic, and therapeutic markers across the spectrum of pediatric malignancies, including leukemias, sarcomas, brain tumors, and embryonal tumors. This panel uses low input amounts of DNA (20 ng) and RNA (20 ng) and is compatible with formalin-fixed, paraffin-embedded and frozen tissue, bone marrow, and peripheral blood. The DNA content of this panel covers the full coding regions of 44 cancer predisposition loci, tumor suppressor genes, and oncogenes; hotspots for mutations in 82 genes; and amplification events in 24 genes. The RNA content includes 1421 targeted gene fusions. We describe the validation of this panel by using a large cohort of 192 unique clinical samples that included a wide range of tumor types and alterations. Robust performance was observed for analytical sensitivity, reproducibility, and limit of detection studies. The results from this study support the use of OncoKids for routine clinical testing of a wide variety of pediatric malignancies.
Molecular Screening for Cancer Treatment Optimization (MOSCATO-01) in Pediatric Patients: A Single-Institutional Prospective Molecular Stratification Trial. [2018]Purpose: This single-institutional feasibility study prospectively characterized genomic alterations in recurrent or refractory solid tumors of pediatric patients to select a targeted therapy.Experimental Design: Following treatment failure, patients with signed consent and ages above 6 months, underwent tumor biopsy or surgical resection of primary or metastatic tumor site. These newly acquired samples were analyzed by comparative genomic hybridization array, next-generation sequencing for 75 target genes, whole-exome and RNA sequencing. Biological significance of the alterations and suggestion of most relevant targeted therapies available were discussed in a multidisciplinary tumor board.Results: From December 2012 to January 2016, 75 patients were included, 73 patients underwent 79 interventions, 56 of which were research biopsies with a low complication rate. All patients were pretreated, 37.0% had a brain tumor, and 63.0% had an extra-cranial solid tumor. Median tumor cell content was 70% (range, 0%-100%). Successful molecular analysis in 69 patients detected in 60.9% of patients an actionable alteration in various oncogenic pathways (42.4% with copy-number change, 33.3% with mutation, 2.1% with fusion), and change in diagnosis in three patients. Fourteen patients received 17 targeted therapies; two had received a matched treatment before inclusion.Conclusions: Research biopsies are feasible in advanced pediatric malignancies that exhibit a considerable amount of potentially actionable alterations. Genetic events affecting different cancer hallmarks and limited access to targeted agents within pediatric clinical trials remain the main obstacles that are addressed in our two subsequent precision medicine studies MAPPYACTS and AcSé-ESMART. Clin Cancer Res; 23(20); 6101-12. ©2017 AACR.
Rates of laboratory adverse events by course in paediatric leukaemia ascertained with automated electronic health record extraction: a retrospective cohort study from the Children's Oncology Group. [2023]Adverse events are often misreported in clinical trials, leading to an incomplete understanding of toxicities. We aimed to test automated laboratory adverse event ascertainment and grading (via the ExtractEHR automated package) to assess its scalability and define adverse event rates for children with acute myeloid leukaemia and acute lymphoblastic leukaemia.
Development of the Precision Link Biobank at Boston Children's Hospital: Challenges and Opportunities. [2020]Increasingly, biobanks are being developed to support organized collections of biological specimens and associated clinical information on broadly consented, diverse patient populations. We describe the implementation of a pediatric biobank, comprised of a fully-informed patient cohort linking specimens to phenotypic data derived from electronic health records (EHR). The Biobank was launched after multiple stakeholders' input and implemented initially in a pilot phase before hospital-wide expansion in 2016. In-person informed consent is obtained from all participants enrolling in the Biobank and provides permission to: (1) access EHR data for research; (2) collect and use residual specimens produced as by-products of routine care; and (3) share de-identified data and specimens outside of the institution. Participants are recruited throughout the hospital, across diverse clinical settings. We have enrolled 4900 patients to date, and 41% of these have an associated blood sample for DNA processing. Current efforts are focused on aligning the Biobank with other ongoing research efforts at our institution and extending our electronic consenting system to support remote enrollment. A number of pediatric-specific challenges and opportunities is reviewed, including the need to re-consent patients when they reach 18 years of age, the ability to enroll family members accompanying patients and alignment with disease-specific research efforts at our institution and other pediatric centers to increase cohort sizes, particularly for rare diseases.
Establishing a translational genomics infrastructure in pediatric cancer: the GREAT KIDS experience. [2019]We have recently established a biobanking and sequencing pipeline at the University of Chicago dubbed Genomics for Risk Evaluation and Anticancer Therapy in Kids. We plan to intersect family and personal history of cancer and other diseases with multidimensional genomic profiling in order to: understand how genetics may have contributed to the development of cancer for each child, and investigate the spectrum of genomic alterations within a tumor spatially (e.g., primary site vs distant metastasis) and over time (e.g., diagnosis vs relapse). This review highlights some of the practical considerations involved in creating such a program including the capacity to use our platform for multi-institutional collaborations.
The Swedish childhood tumor biobank: systematic collection and molecular characterization of all pediatric CNS and other solid tumors in Sweden. [2023]The Swedish Childhood Tumor Biobank (BTB) is a nonprofit national infrastructure for collecting tissue samples and genomic data from pediatric patients diagnosed with central nervous system (CNS) and other solid tumors. The BTB is built on a multidisciplinary network established to provide the scientific community with standardized biospecimens and genomic data, thereby improving knowledge of the biology, treatment and outcome of childhood tumors. As of 2022, over 1100 fresh-frozen tumor samples are available for researchers. We present the workflow of the BTB from sample collection and processing to the generation of genomic data and services offered. To determine the research and clinical utility of the data, we performed bioinformatics analyses on next-generation sequencing (NGS) data obtained from a subset of 82 brain tumors and patient blood-derived DNA combined with methylation profiling to enhance the diagnostic accuracy and identified germline and somatic alterations with potential biological or clinical significance. The BTB procedures for collection, processing, sequencing, and bioinformatics deliver high-quality data. We observed that the findings could impact patient management by confirming or clarifying the diagnosis in 79 of the 82 tumors and detecting known or likely driver mutations in 68 of 79 patients. In addition to revealing known mutations in a broad spectrum of genes implicated in pediatric cancer, we discovered numerous alterations that may represent novel driver events and specific tumor entities. In summary, these examples reveal the power of NGS to identify a wide number of actionable gene alterations. Making the power of NGS available in healthcare is a challenging task requiring the integration of the work of clinical specialists and cancer biologists; this approach requires a dedicated infrastructure, as exemplified here by the BTB.
Molecular residual disease status at the end of chemotherapy fails to predict subsequent relapse in children with B-lineage acute lymphoblastic leukemia. [2017]We have investigated whether the extent of residual leukemia in the marrows obtained at the completion of chemotherapy can predict subsequent relapse in children with B-lineage acute lymphoblastic leukemia (ALL).
Design and Validation of a Custom Next-Generation Sequencing Panel in Pediatric Acute Lymphoblastic Leukemia. [2023]The molecular landscape of acute lymphoblastic leukemia (ALL) is highly heterogeneous, and genetic lesions are clinically relevant for diagnosis, risk stratification, and treatment guidance. Next-generation sequencing (NGS) has become an essential tool for clinical laboratories, where disease-targeted panels are able to capture the most relevant alterations in a cost-effective and fast way. However, comprehensive ALL panels assessing all relevant alterations are scarce. Here, we design and validate an NGS panel including single-nucleotide variants (SNVs), insertion-deletions (indels), copy number variations (CNVs), fusions, and gene expression (ALLseq). ALLseq sequencing metrics were acceptable for clinical use and showed 100% sensitivity and specificity for virtually all types of alterations. The limit of detection was established at a 2% variant allele frequency for SNVs and indels, and at a 0.5 copy number ratio for CNVs. Overall, ALLseq is able to provide clinically relevant information to more than 83% of pediatric patients, making it an attractive tool for the molecular characterization of ALL in clinical settings.
Roadmap to Liquid Biopsy Biobanking from Pediatric Cancers-Challenges and Opportunities. [2021]Liquid biopsy is rapidly gaining traction for potentially revolutionizing cancer diagnosis and treatment through blood-based utilization of shed biomolecules. This approach can provide a global picture of the cancer in real time, at multiple time points, and with minimal invasiveness. In this review, we familiarize cancer biobanks with the principles used for liquid biopsy work and highlight unique aspects of applying liquid biopsy approaches to pediatric cancers to enable high-quality and efficient translational research.