Leukemia, Acute LymphoblasticNCT02580981
Acute Lymphoblastic Leukemia Therapies Informed by Genomic Analyses
A study testing Acute Lymphobastic Leukemia (ALL) Treatment Options in people with Leukemia, Acute Lymphoblastic, run by New Mexico Cancer Research Alliance at 1 site in United States.
Trial 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). Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Leukemia, Acute Lymphoblastic
- What is being tested?
- Acute Lymphobastic Leukemia (ALL) Treatment Options
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 21 participants
- Where
- 1 siteUnited States
- Study dates
- 28 Jul 2016to 20 Oct 2022
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Any age
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- Previous therapy, excluding emergency radiation, steroids or intrathecal cytarabine
- Not willing to obtain cancer care at the University of New Mexico
Trial locations and contacts
1 site in 1 country.
United States1 site
University of New Mexico Comprehensive Cancer Center
Albuquerque, New Mexico, 87131
About this study
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.
Read the detailed description
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.
- Conditions
- Leukemia, Acute Lymphoblastic
- Being tested
- Acute Lymphobastic Leukemia (ALL) Treatment Options
- Keywords
- Cancer, Oncology, Acute Lymphoblastic Leukemia, ALL, Genomics, Genetics, Sequencing, DNA, RNA, Ph-like
- Medical subject headings
- Precursor Cell Lymphoblastic Leukemia-Lymphoma, Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Acute Lymphobastic Leukemia (ALL) Treatment OptionsOther
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.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Other: Acute Lymphobastic Leukemia (ALL) Treatment Options |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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).
Measured: 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)
Measured: 3 years
Secondary outcomes (4)
Relationship of patient characteristics to trial enrollment
Genetic and molecular characterization as described for the Primary Outcome Measures will be summarized for patients who are enrolled on NCTN clinical trials and for those who are not enrolled on NCTN clinical trials. The two group comparisons (NCTN vs. non-NCTN) will be tested using non-parametric approach such as Wilcoxon sum rank test.
Measured: 3 years
Relationship between race/ethnicity and outcome
Time-to-event data (such as Progression free survival (PFS), determined clinically) will be summarized using Kaplan-Meier curves along with log-rank test by the treatment groups as well as race/ethnicity determined through molecular assessment of genetic ancestry as described in Primary Outcome Measure 3. Multivariable Cox Proportional Hazards model will also be explored for PFS with treatment and/or ethnicity variables.
Measured: 3 years
Feasibility of discovering molecular features in ALL with therapeutic relevance
Feasibility will be assessed by calculation of the following statistics: percent of patients who enrolled in NCTN trials, percent of patients with minimal residual disease (MRD) that are completely evaluated over time, percent of patients for whom molecularly characterization is feasible and informative over the treatment course. All estimated proportions will be accompanied by exact 95% confidence intervals
Measured: 3 years
Minimal Residual Disease (MRD) evaluation
End-induction Minimal Residual Disease (MRD) will be performed using a Clinical Laboratory Improvement Amendments (CLIA)-approved flow-cytometric assay at the Children's Oncology Group University of Washington Reference Laboratory. Molecular MRD will also be determined using research-based deep sequencing. MRD repeatedly measured across time points will be summarized using descriptive statistics (bar graph for High vs. Low status). Associations between the MRD and the treatment groups (LAD Positive vs. LAD Negative for NCTN and Non-NCTN treatment groups), using the exact Pearson Chi-Square test with Monte Carlo simulation at each time point will be assessed.
Measured: 3 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Oct 2015 (estimated)
- Study start28 Jul 2016
- Primary completion19 Mar 2022
- Study completion20 Oct 2022
Why it stopped: Staffing
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Leukemia, Acute LymphoblasticStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 21 participants (actual)
Sponsor and investigators
- Lead sponsor
- New Mexico Cancer Research Alliance
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Jodi Mayfield, MD, Principal investigator, University of New Mexico, Department of Pediatrics
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02580981
- Sponsor's protocol ID
- INST UNM 1503
- Status last verified
- Jan 2024
- First submitted
- 5 Oct 2015
- Last updated
- 11 Jan 2024
- Results posted
- No
- Data monitoring committee
- Yes
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 11 Jan 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Acute Lymphoblastic Leukemia Therapies Informed by Genomic Analyses
- ClinicalTrials.gov ID
- NCT02580981
- Acronym / sponsor ID
- INST UNM 1503
- Conditions
- Leukemia, Acute Lymphoblastic
- Keywords
- Cancer, Oncology, Acute Lymphoblastic Leukemia, ALL, Genomics, Genetics, Sequencing, DNA
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Staffing
- Enrolment
- 21 participants (actual)
- Lead sponsor
- New Mexico Cancer Research AllianceUniversity, hospital or other
- Study start
- 28 Jul 2016 (actual)
- Primary completion
- 19 Mar 2022 (actual)
- Study completion
- 20 Oct 2022 (actual)
- First posted
- 20 Oct 2015 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Genomic Testing | Experimental | Other: Acute Lymphobastic Leukemia (ALL) Treatment OptionsNewly 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. |
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (4 listed)
- 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.
Key exclusion criteria (2 listed)
- Previous therapy, excluding emergency radiation, steroids or intrathecal cytarabine
- Not willing to obtain cancer care at the University of New Mexico
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Acute Lymphobastic Leukemia (ALL) Treatment OptionsDepending 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. | Other | Genomic Testing |
Primary outcome
ALL characterization: Low Density Array
Time frame: 3 years
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.
ALL characterization: Next Generation Sequencing
Time frame: 3 years
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).
ALL characterization: SNP analysis
Time frame: 3 years
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)
4 secondary outcomes
Relationship of patient characteristics to trial enrollment
Time frame: 3 years
Relationship between race/ethnicity and outcome
Time frame: 3 years
Feasibility of discovering molecular features in ALL with therapeutic relevance
Time frame: 3 years
Minimal Residual Disease (MRD) evaluation
Time frame: 3 years
Results and safety
The study was stopped early (reason given: Staffing). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Jan 2024.
- University of New Mexico Comprehensive Cancer CenterLink provided by the sponsor.
- New Mexico Cancer Care AllianceLink provided by the sponsor.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Jodi Mayfield, MD principal investigator
University of New Mexico, Department of Pediatrics
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Acute Lymphobastic Leukemia (ALL) Treatment Options in people with Leukemia, Acute Lymphoblastic, run by New Mexico Cancer Research Alliance at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 2 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 11 Jan 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study was stopped early (reason given: Staffing). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
ALL characterization: Low Density Array (time frame: 3 years). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 Jan 2024.