Acute Lymphoblastic Leukemia Therapies Informed by Genomic Analyses

NCT02580981 | Terminated DMC

• 1 other identifier: INST UNM 1503
• Study Type: interventional
• Target: 21
• Locations: 1 country
• Sites: 1

Brief Summary

Previous work performed by University of New Mexico Comprehensive Cancer Center (UNMCCC) investigators has revealed previously unknown genomic mutations in children, adolescents, and young adults with high-risk B and T cell precursor acute lymphoblastic leukemia (ALL). Using genomic and next generation DNA sequencing technologies, these investigators revealed that 14% of children with high-risk ALL have "Philadelphia chromosome-like" ("Ph-like") ALL. Patients with this form of ALL were found to have a significantly increased risk of treatment failure and death. Further work revealed that there are more than 40 distinct gene rearrangements and fusions that can result in Ph-like ALL. Cell lines and human leukemic cells expressing some of these different gene fusions were sensitive to currently available drugs. This suggests that Ph-like ALL patients with these specific distinct gene fusions should be targeted in future clinical trials to be treated with appropriate therapy. Further work is also needed to identify other potentially targetable genetic alterations in ALL patients. Therefore, the goal of this study is to perform genomic screening of all newly diagnosed ALL patients seen at UNM and to use this information to enroll patients onto available National Clinical Trial Network (NCTN) clinical trials. If an appropriate NCTN trial is not available, best clinical management will be pursued.

Conditions

Leukemia, Acute Lymphoblastic

Keywords

Cancer; Oncology; Acute Lymphoblastic Leukemia; ALL; Genomics; Genetics; Sequencing; DNA; RNA; Ph-like

Outcome Measures

Primary Outcomes (3)

• ALL characterization: Low Density Array

  Newly diagnosed ALL patients at UNMCCC will undergo Low Density Array (LDA) card screening (a gene expression classifier for Ph-like ALL) at initial diagnosis. The proportion of LDA status (positive vs. negative) and its 95% confidence interval will be calculated based on the exact binomial distribution.

  3 years

• ALL characterization: Next Generation Sequencing

  Newly diagnosed ALL patients at UNMCCC will undergo Next Generation Sequencing (NGS) at initial diagnosis. NGS (exomic and transcriptomic) of a sufficient read depth (500-700x) will be employed to detect clonal heterogeneity at diagnosis. Statistical analysis will be primarily descriptive (e.g. frequency (proportion) of various mutations will be calculated).

  3 years

• ALL characterization: SNP analysis

  Newly diagnosed ALL patients at UNMCCC will undergo Molecular Determination of Genetic Ancestry (using a panel of single nucleotide polymorphisms (SNPs)) at initial diagnosis. Statistical analysis will be primarily descriptive (e.g. frequency (proportion) of SNPs and genetic ancestry groups will be calculated)

  3 years

Secondary Outcomes (4)

• Relationship of patient characteristics to trial enrollment

  3 years

• Relationship between race/ethnicity and outcome

  3 years

• Feasibility of discovering molecular features in ALL with therapeutic relevance

  3 years

• Minimal Residual Disease (MRD) evaluation

  3 years

Study Arms (1)

Genomic Testing

EXPERIMENTAL

Newly diagnosed ALL patients will undergo genomic studies listed in Primary Objective 1. Analyses will be performed on a bone marrow (BM) aspirate at initial diagnosis (patients with an absolute blast count of at least 1,000/μL, may submit 2 mL of peripheral blood at diagnosis for each 1 mL of required BM. In patients in whom the aspirate cannot be obtained, a core biopsy will be used). In addition, flow cytometric analysis and deep sequencing will be used to characterize and monitor the molecular heterogeneity and clonal evolution of disease during front-line therapy. BM, blood, and buccal specimens will be collected on day 29 of induction treatment and possibly at a later time point if relapse occurs.

Other: Acute Lymphobastic Leukemia (ALL) Treatment Options

Interventions

Acute Lymphobastic Leukemia (ALL) Treatment Options OTHER

Depending on the genomic testing results, patients with targetable genomic lesions will be enrolled onto available national clinical trials that are sponsored by the NCI National Clinical Trials Network (NCTN) (COG and other adult NCI Cooperative Groups). If no suitable NCTN trial exists, appropriate therapeutic regimens (including currently accepted standards-of-care), alterations in therapy, or treatment with targeted agents to specific genomic lesions will be considered.

Genomic Testing

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• New diagnosis of Acute Lymphoblastic Leukemia
• No previous therapy, excluding emergency radiation, steroids or intrathecal cytarabine
• Any age
• Ability to understand and the willingness to sign a written informed consent document.

You may not qualify if:

• Previous therapy, excluding emergency radiation, steroids or intrathecal cytarabine
• Not willing to obtain cancer care at the University of New Mexico

Sponsors & Collaborators

• New Mexico Cancer Research Alliance: lead

Study Sites (1)

University of New Mexico Comprehensive Cancer Center

Albuquerque, New Mexico, 87131, United States

Location

Related Links

• University of New Mexico Comprehensive Cancer Center
• New Mexico Cancer Care Alliance

MeSH Terms

Conditions

Precursor Cell Lymphoblastic Leukemia-Lymphoma; Neoplasms

Condition Hierarchy (Ancestors)

Leukemia, Lymphoid; Leukemia; Neoplasms by Histologic Type; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Study Officials

• Jodi Mayfield, MD

  University of New Mexico, Department of Pediatrics

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 5, 2015
• First Posted: October 20, 2015
• Study Start: July 28, 2016
• Primary Completion: March 19, 2022
• Study Completion: October 20, 2022
• Last Updated: January 11, 2024

Record last verified: 2024-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)