"Triple Negative" Adult B-cell Acute Lymphoblastic Leukemia - TRINEG-ALL

NCT ID: NCT06919393

Last Updated: 2025-04-09

Basic Information

• Recruitment Status: RECRUITING
• Total Enrollment: 60 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2019-10-23
• Study Completion Date: 2026-01-31

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.

Conditions

Leukemia, Lymphoblastic

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: PROSPECTIVE

Study Groups

"Triple negative" adul B-cell ALL

Prospective and retrospective cohorts.

"Triple negative" adul B-cell ALL

Intervention Type: OTHER

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

Interventions

"Triple negative" adul B-cell ALL

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

Intervention Type: OTHER

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;

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Istituto Romagnolo per lo Studio dei Tumori Dino Amadori IRST S.r.l. IRCCS

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Giovanni Martinelli, Prof

Role: STUDY_DIRECTOR

IRST IRCCS

Locations

Irst Irccs

Meldola, FC, Italy

Site Status: RECRUITING

Ospedale S. Maria delle Croci RAVENNA

Ravenna, RA, Italy

Site Status: RECRUITING

Ospedale Infermi

Rimini, RN, Italy

Site Status: RECRUITING

Countries

Italy

Central Contacts

Oriana Nanni, Dr

Role: CONTACT

oriana.nanni@irst.emr.it

+39 0543739100

Anna Ferrari, Dr

Role: CONTACT

anna.ferrari@irst.emr.it

0543739909

Facility Contacts

Anna Ferrari, Dr

Role: primary

Other Identifiers

IRSTB098

Identifier Type: -

Identifier Source: org_study_id