Clinical trial NCT06919393: "Triple Negative" Adult B-cell Acute Lymphoblastic Leukemia - TRINEG-ALL
Official title: "Triple Negative" Adult B-cell Acute Lymphoblastic Leukemia: Molecular Characterization, Identification and New Stratification
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Leukemia, Lymphoblastic
Keywords: lymphoblastic acute leukemia (LAL)
triple negative
B cell
Lead sponsor: Istituto Romagnolo per lo Studio dei Tumori Dino Amadori IRST S.r.l. IRCCS
Sponsor class: OTHER
First posted: 2025-04-09
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
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.

Brief 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.

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.

Eligibility criteria: Inclusion Criteria:

* 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.

Exclusion Criteria:

* 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;

Primary outcomes:
measure: Biological characterization for B-ALL Ph-/-/- subgroup identification
timeFrame: 3 years
Secondary outcomes:
measure: Correlation, in terms of survival, between identified Ph-/-/- molecular subgroups and eventual novel associated molecular features.
timeFrame: 3 years
measure: Cytofluorimetric evaluation of Ph-/-/- ALL markers as CRLF2, CTGF and CD200.
timeFrame: 3 years
measure: Discover new biomarkers identified Ph-/-/- molecular subgroups
timeFrame: 3 years
Other outcomes:
Locations:
city: Meldola
country: Italy
facility: Irst Irccs
state: FC
city: Ravenna
country: Italy
facility: Ospedale S. Maria delle Croci RAVENNA
state: RA
city: Rimini
country: Italy
facility: Ospedale Infermi
state: RN
Study officials:
affiliation: IRST IRCCS
name: Giovanni Martinelli, Prof
role: STUDY_DIRECTOR
References: