Acute Lymphoblastic Leukemia Therapies Informed by Genomic Analyses
| Status: | Recruiting |
|---|---|
| Conditions: | Blood Cancer |
| Therapuetic Areas: | Oncology |
| Healthy: | No |
| Age Range: | Any |
| Updated: | 12/23/2018 |
| Start Date: | July 2016 |
| End Date: | December 2021 |
| Contact: | Jodi Mayfield, MD |
| Email: | jrmayfield@salud.unm.edu |
| Phone: | 505-272-4461 |
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.
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.
The work performed by UNMCCC investigators and others as described briefly above has provided
major insights into the biologic and clinical features and the genomic landscape of Ph-like
ALL, which is strikingly heterogeneous. Gene expression profiling and RNA/transcriptomic,
exome, and whole genome sequencing have identified several distinct subclasses of kinase
activating lesions in 91% of the Ph-like ALL cases studied to date, most commonly kinase and
cytokine receptor gene rearrangements and fusions. UNMCCC investigators are now collaborating
with Children's Oncology Group (COG) and the adult National Cancer Institute (NCI)
Cooperative Groups (Southwest Oncology Group (SWOG), Eastern Cooperative Oncology Group
(ECOG) - American College of Radiology Imaging Network (ACRIN), The Alliance) to develop
national clinical trials for pediatric, adolescent and young adult (AYA), and adult ALL
patients that incorporate their genomic diagnostic screens, molecular diagnostics, and next
generation sequencing studies to identify underlying genomic lesions in ALL and target
patients to appropriate therapeutic regimens.
In this feasibility study, next generation sequencing (NGS) technologies will inform an acute
lymphoblastic leukemia risk classification system, which may be adapted to identify patients
who might benefit from targeted therapies; such patients will be targeted to NCTN National
Treatment trials or UNMCCC-sponsored trials where appropriate, through detailed genomic data
analysis performed under College of American Pathologists (CAP)/CLIA conditions and in
individual case discussions in a Molecular Tumor Board.
In addition, the association of race and ethnicity with the spectrum of ALL-associated
genomic mutations in the New Mexico and regional ALL population, which includes a significant
proportion of underrepresented minorities, will be studied. This may ultimately allow for the
development of an ancestry-based risk classification system.
major insights into the biologic and clinical features and the genomic landscape of Ph-like
ALL, which is strikingly heterogeneous. Gene expression profiling and RNA/transcriptomic,
exome, and whole genome sequencing have identified several distinct subclasses of kinase
activating lesions in 91% of the Ph-like ALL cases studied to date, most commonly kinase and
cytokine receptor gene rearrangements and fusions. UNMCCC investigators are now collaborating
with Children's Oncology Group (COG) and the adult National Cancer Institute (NCI)
Cooperative Groups (Southwest Oncology Group (SWOG), Eastern Cooperative Oncology Group
(ECOG) - American College of Radiology Imaging Network (ACRIN), The Alliance) to develop
national clinical trials for pediatric, adolescent and young adult (AYA), and adult ALL
patients that incorporate their genomic diagnostic screens, molecular diagnostics, and next
generation sequencing studies to identify underlying genomic lesions in ALL and target
patients to appropriate therapeutic regimens.
In this feasibility study, next generation sequencing (NGS) technologies will inform an acute
lymphoblastic leukemia risk classification system, which may be adapted to identify patients
who might benefit from targeted therapies; such patients will be targeted to NCTN National
Treatment trials or UNMCCC-sponsored trials where appropriate, through detailed genomic data
analysis performed under College of American Pathologists (CAP)/CLIA conditions and in
individual case discussions in a Molecular Tumor Board.
In addition, the association of race and ethnicity with the spectrum of ALL-associated
genomic mutations in the New Mexico and regional ALL population, which includes a significant
proportion of underrepresented minorities, will be studied. This may ultimately allow for the
development of an ancestry-based risk classification system.
Inclusion Criteria:
- 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.
Exclusion Criteria:
- Previous therapy, excluding emergency radiation, steroids or intrathecal cytarabine
- Not willing to obtain cancer care at the University of New Mexico
We found this trial at
1
site
Albuquerque, New Mexico 87131
Principal Investigator: Jodi Mayfield, MD
Phone: 505-925-0390
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