Leukemia, LymphoblasticTRINEG-ALLNCT06919393
"Triple Negative" Adult B-cell Acute Lymphoblastic Leukemia - TRINEG-ALL
An observational study of Leukemia, Lymphoblastic, run by Istituto Romagnolo per lo Studio dei Tumori Dino Amadori IRST S.r.l. IRCCS at 3 sites in Italy.
Trial summary
It is a multicenter, non-interventional, non pharmacological, translational, prospective study. Any decision about drug administration is made by the physician based on his clinical judgment in the context of clinical practice, independently from the decision to include the patient in the study. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Leukemia, Lymphoblastic
- What is being tested?
- "Triple negative" adul B-cell ALL
- How many people
- 60 participants
- Where
- 3 sitesItaly
- Study dates
- 23 Oct 2019to Jan 2026
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: Patients diagnosed with Ph-/-/- B cell Acute Lymphoblastic Leukemia (see inclusion criteria) will be considered for enrolment. Therefore, patients can be enrolled at diagnosis or relapse/s. About 60 patients affected by primary or secondary B-ALL, at diagnosis and/or relapse/s will be enrolled in this study. All suitable prospective fresh PB and/or BM samples will be evaluated with cytofluorimetric panel.
Who may be able to join
- Participant is willing and able to give informed consent for participation in the study;
- Patients with new diagnosis and/or relapse/s of primary or secondary B-ALL;
- Negative for BCR-ABL1 t(9;22); TCF3-PBX1 t(1;19); MLL-AF4 t(4;11) rearrangements;
- Participant is willing and able to give informed consent for participation in the study;
- Male or Female, aged >18 years;
- Availability of clinical data.
Who cannot join
- Age < 18 years;
- B-ALL positive for BCR-ABL1 t(9;22); TCF3-PBX1 t(1;19); MLL-AF4 t(4;11) rearrangements.
- Low blast percentage (<70%) samples could be excluded for molecular evaluations, not for cytofluorimetric analyses;
Trial locations and contacts
3 sites in 1 country. Contact the study team or a site near you to ask about taking part.
Italy3 sites, 3 recruiting
- Recruiting
Irst Irccs
Meldola, FC, 47014
Anna Ferrari, Dr
- Recruiting
Ospedale S. Maria delle Croci RAVENNA
Ravenna, RA, 48121
- Recruiting
Ospedale Infermi
Rimini, RN, 47923
About this study
Official title: "Triple Negative" Adult B-cell Acute Lymphoblastic Leukemia: Molecular Characterization, Identification and New Stratification
It is a multicenter, non-interventional, non pharmacological, translational, prospective study. Any decision about drug administration is made by the physician based on his clinical judgment in the context of clinical practice, independently from the decision to include the patient in the study.
Read the detailed description
Survival rates from Acute lymphoblastic leukemia (ALL) have improved dramatically over the past four decades but vary significantly with age. Children treated on modern protocols have survival rates exceeding 90%. Although the remarkable progress made in the treatment of B-Acute lymphoblastic leukemia (B-ALL) in children and, with less efficacy, in adults, several ALL subtypes continue to have a poor prognosis and in a proportion of long-term surviving patients, treatment is responsible for short and long-term toxicities. Consequently, there is a need in improving the molecular dissection of subtypes, identifying genetic alterations that predict the risk of treatment failure and developing novel and targeted therapies. B-ALL patients that doesn't have the most recurrent adult rearrangements (breakpoint cluster region (BCR) - Abelson murine leukemia viral oncogene homolog 1 (ABL1) t(9;22); Transcription Factor 3 (TCF3) - Pre-B-cell leukemia transcription factor 1(PBX1) t(1;19); mixed-lineage leukemia 1 (MLL) - ALL1-fused gene from chromosome 4 (AF4) t(4;11)) are collectively referred to as triple negative (Ph-/-/-) ALL (that represents 61% of adult B-ALL; Roberts KG, J Clinical Oncology 2016). Triple negative ALL is a heterogeneous group of patients; most of these patients have a poor prognosis and miss a target therapy. In the last few years the role of CRLF2 (cytokine receptor-like factor 2; a type I cytokine receptor) gene have become pivotal in ALL, both in adult and paediatric patients. In the last few years the role of CRLF2 (cytokine receptor-like factor 2; a type I cytokine receptor) gene have become pivotal in ALL, both in adult and paediatric patients. CRLF2 is frequently altered in adult B-ALL, especially in Ph-like pts (50-75% of cases) and in Down syndrome ALL (50% to 55%). Alterations that lead, in the majority of cases, to a CRLF2 overexpression. Adult pts with upregulated CRLF2 have poor outcome and novel strategies are needed to improve it.
It is a multicenter, non-interventional, non pharmacological, translational, prospective study. Any decision about drug administration is made by the physician based on his clinical judgment in the context of clinical practice, independently from the decision to include the patient in the study.
The primary objective is the biological characterization of Ph-/-/- ALL, considering CRLF2 overexpression event, in order to define cluster of patients and to assess biomarkers in this subgroup to test new drugs.
The secondary objective is to evaluate if the cytofluorimetric assay - developed on the basis of preliminary data - may be used to detect triple negative subgroups, to provide a rapid, simple and economically viable diagnostic tool to recognize these cases at presentation.
About 60 patients affected by primary or secondary ALL will be enrolled at diagnosis and/or relapse/s.
Patients will be asked to donate part of the Peripheral Blood and Bone Marrow samples, collected according to clinical practice for the management of their disease, for the purposes of this study. A saliva sample will be collected from each patients. Clinical data will be collected in a study dedicated database.
The total duration of the study is 36 months.
- Conditions
- Leukemia, Lymphoblastic
- Being tested
- "Triple negative" adul B-cell ALL
- Keywords
- lymphoblastic acute leukemia (LAL), triple negative, B cell
- Medical subject headings
- Precursor Cell Lymphoblastic Leukemia-Lymphoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
"Triple negative" adul B-cell ALLOther
Samples will be studied with conventional techniques to classify and define properly the disease: morphology, immunophenotype, immunohistochemistry (IHC), conventional Cytogenetic Fluorescence in Situ Hybridization (FISH) will be used when appropriate.
● Isolation of Mononuclear cells
The following research methodologies will be applied:
- Next Generation Sequencing
- Flow cytometry analysis of 3C-up B-ALL top three markers
- Gene expression profile analysis
- Copy number Alterations analysis
- In vitro studies
| Study group | Role | What they receive |
|---|---|---|
| "Triple negative" adul B-cell ALL | Prospective and retrospective cohorts. Receives: Other: "Triple negative" adul B-cell ALL |
What is being measured
The primary outcome is the main question the study is designed to answer.
Biological characterization for B-ALL Ph-/-/- subgroup identification
Biological characterization of Ph-/-/- ALL, considering CRLF2 overexpression event, to better define clusters preliminarily identified and to identify biomarkers in these subgroups. Each sample at diagnosis and/or relapse time-point will be sequenced with an RNA-seq capture approach. Through bioinformatic analysis we will identify upregulated CRLF2 samples and associated gene signature. Fusion, mutation identification will integrate expression data.
Measured: 3 years
Secondary outcomes (3)
Correlation, in terms of survival, between identified Ph-/-/- molecular subgroups and eventual novel associated molecular features.
To investigate the association of identified Ph-/-/- molecular subgroups and/or molecular features with the clinical outcome (OS, EFS). To assess if a Ph-/-/- molecular subgroups, identified thanks to our analyses, could be associated with poor prognosis.
Measured: 3 years
Cytofluorimetric evaluation of Ph-/-/- ALL markers as CRLF2, CTGF and CD200.
To evaluate if the cytofluorimetric assay - developed on the basis of preliminary data - may be used to detect triple negative subgroups, to provide a rapid, simple and economically viable diagnostic tool to recognize these cases at presentation. On each enrolled fresh sample cells will be analysed through a B-ALL flow cytometer panel (e.g. CD45, CD19, CD34) to which markers of interest will be added (e.g. CRLF2, CTGF and CD200).
Their expression in flow cytometry will be compared with the expression obtained from RNA-seq data.
Measured: 3 years
Discover new biomarkers identified Ph-/-/- molecular subgroups
To assess if some molecular feature could be associated to specific Ph-/-/- molecular subgroups. To explore if these biomarkers, detected in some of identified Ph-/-/- molecular subgroups, could be targeted by novel drugs. To evaluate the drug/s effects through sensitivity in vitro/ex vivo tests on B-ALL cell lins and on primary leukemic cells.
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 posted9 Apr 2025
- Study start23 Oct 2019
- Primary completionJan 2026 (estimated)
- Study completionJan 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Leukemia, 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
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 60 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Istituto Romagnolo per lo Studio dei Tumori Dino Amadori IRST S.r.l. IRCCS
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Giovanni Martinelli, Prof, Study director, IRST IRCCS
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06919393
- Sponsor's protocol ID
- IRSTB098
- Acronym
- TRINEG-ALL
- Status last verified
- Apr 2025
- First submitted
- 25 Feb 2021
- Last updated
- 9 Apr 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 9 Apr 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- "Triple Negative" Adult B-cell Acute Lymphoblastic Leukemia: Molecular Characterization, Identification and New Stratification
- ClinicalTrials.gov ID
- NCT06919393
- Acronym / sponsor ID
- TRINEG-ALL / IRSTB098
- Conditions
- Leukemia, Lymphoblastic
- Keywords
- lymphoblastic acute leukemia (LAL), triple negative, B cell
- Study type
- Observational
- Recruitment status
- Recruiting
- Enrolment
- 60 participants (estimated)
- Lead sponsor
- Istituto Romagnolo per lo Studio dei Tumori Dino Amadori IRST S.r.l. IRCCSUniversity, hospital or other
- Study start
- 23 Oct 2019 (actual)
- Primary completion
- Jan 2026 (estimated)
- Study completion
- Jan 2026 (estimated)
- First posted
- 9 Apr 2025 (actual)
- 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.
It is a multicenter, non-interventional, non pharmacological, translational, prospective study. Any decision about drug administration is made by the physician based on his clinical judgment in the context of clinical practice, independently from the decision to include the patient in the study.
Detailed description
Survival rates from Acute lymphoblastic leukemia (ALL) have improved dramatically over the past four decades but vary significantly with age. Children treated on modern protocols have survival rates exceeding 90%. Although the remarkable progress made in the treatment of B-Acute lymphoblastic leukemia (B-ALL) in children and, with less efficacy, in adults, several ALL subtypes continue to have a poor prognosis and in a proportion of long-term surviving patients, treatment is responsible for short and long-term toxicities. Consequently, there is a need in improving the molecular dissection of subtypes, identifying genetic alterations that predict the risk of treatment failure and developing novel and targeted therapies. B-ALL patients that doesn't have the most recurrent adult rearrangements (breakpoint cluster region (BCR) - Abelson murine leukemia viral oncogene homolog 1 (ABL1) t(9;22); Transcription Factor 3 (TCF3) - Pre-B-cell leukemia transcription factor 1(PBX1) t(1;19); mixed-lineage leukemia 1 (MLL) - ALL1-fused gene from chromosome 4 (AF4) t(4;11)) are collectively referred to as triple negative (Ph-/-/-) ALL (that represents 61% of adult B-ALL; Roberts KG, J Clinical Oncology 2016). Triple negative ALL is a heterogeneous group of patients; most of these patients have a poor prognosis and miss a target therapy. In the last few years the role of CRLF2 (cytokine receptor-like factor 2; a type I cytokine receptor) gene have become pivotal in ALL, both in adult and paediatric patients. In the last few years the role of CRLF2 (cytokine receptor-like factor 2; a type I cytokine receptor) gene have become pivotal in ALL, both in adult and paediatric patients. CRLF2 is frequently altered in adult B-ALL, especially in Ph-like pts (50-75% of cases) and in Down syndrome ALL (50% to 55%). Alterations that lead, in the majority of cases, to a CRLF2 overexpression. Adult pts with upregulated CRLF2 have poor outcome and novel strategies are needed to improve it.
It is a multicenter, non-interventional, non pharmacological, translational, prospective study. Any decision about drug administration is made by the physician based on his clinical judgment in the context of clinical practice, independently from the decision to include the patient in the study.
The primary objective is the biological characterization of Ph-/-/- ALL, considering CRLF2 overexpression event, in order to define cluster of patients and to assess biomarkers in this subgroup to test new drugs.
The secondary objective is to evaluate if the cytofluorimetric assay - developed on the basis of preliminary data - may be used to detect triple negative subgroups, to provide a rapid, simple and economically viable diagnostic tool to recognize these cases at presentation.
About 60 patients affected by primary or secondary ALL will be enrolled at diagnosis and/or relapse/s.
Patients will be asked to donate part of the Peripheral Blood and Bone Marrow samples, collected according to clinical practice for the management of their disease, for the purposes of this study. A saliva sample will be collected from each patients. Clinical data will be collected in a study dedicated database.
The total duration of the study is 36 months.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| "Triple negative" adul B-cell ALL | – | Other: "Triple negative" adul B-cell ALLProspective and retrospective cohorts. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Patients diagnosed with Ph-/-/- B cell Acute Lymphoblastic Leukemia (see inclusion criteria) will be considered for enrolment. Therefore, patients can be enrolled at diagnosis or relapse/s. About 60 patients affected by primary or secondary B-ALL, at diagnosis and/or relapse/s will be enrolled in this study. All suitable prospective fresh PB and/or BM samples will be evaluated with cytofluorimetric panel.
Key inclusion criteria (6 listed)
- Participant is willing and able to give informed consent for participation in the study;
- Patients with new diagnosis and/or relapse/s of primary or secondary B-ALL;
- Negative for BCR-ABL1 t(9;22); TCF3-PBX1 t(1;19); MLL-AF4 t(4;11) rearrangements;
- Participant is willing and able to give informed consent for participation in the study;
- Male or Female, aged >18 years;
Key exclusion criteria (3 listed)
- Age < 18 years;
- B-ALL positive for BCR-ABL1 t(9;22); TCF3-PBX1 t(1;19); MLL-AF4 t(4;11) rearrangements.
- Low blast percentage (<70%) samples could be excluded for molecular evaluations, not for cytofluorimetric analyses;
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 |
|---|---|---|
| "Triple negative" adul B-cell ALLSamples will be studied with conventional techniques to classify and define properly the disease: morphology, immunophenotype, immunohistochemistry (IHC), conventional Cytogenetic Fluorescence in Situ Hybridization (FISH) will be used when appropriate. ● Isolation of Mononuclear cells The following research methodologies will be applied: * Next Generation Sequencing * Flow cytometry analysis of 3C-up B-ALL top three markers * Gene expression profile analysis * Copy number Alterations analysis * In vitro studies | Other | "Triple negative" adul B-cell ALL |
Primary outcome
Biological characterization for B-ALL Ph-/-/- subgroup identification
Time frame: 3 years
Biological characterization of Ph-/-/- ALL, considering CRLF2 overexpression event, to better define clusters preliminarily identified and to identify biomarkers in these subgroups. Each sample at diagnosis and/or relapse time-point will be sequenced with an RNA-seq capture approach. Through bioinformatic analysis we will identify upregulated CRLF2 samples and associated gene signature. Fusion, mutation identification will integrate expression data.
3 secondary outcomes
Correlation, in terms of survival, between identified Ph-/-/- molecular subgroups and eventual novel associated molecular features.
Time frame: 3 years
Cytofluorimetric evaluation of Ph-/-/- ALL markers as CRLF2, CTGF and CD200.
Time frame: 3 years
Discover new biomarkers identified Ph-/-/- molecular subgroups
Time frame: 3 years
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Apr 2025.
- 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.
Giovanni Martinelli, Prof study director
IRST IRCCS
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Leukemia, Lymphoblastic, run by Istituto Romagnolo per lo Studio dei Tumori Dino Amadori IRST S.r.l. IRCCS at 3 sites in Italy.
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 6 inclusion and 3 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: looking for participants now, as of the sponsor's last update on 9 Apr 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in Italy. 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?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Oriana Nanni, Dr (+39 0543739100, oriana.nanni@irst.emr.it), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Biological characterization for B-ALL Ph-/-/- subgroup identification (time frame: 3 years). 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 9 Apr 2025.