Clinical trial NCT05832125: Registry of Relapsed/Refractory T-cell Acute Lymphoblastic Leukemia
Official title: Observatory for Patients Treated for Relapsed or Refractory T-cell Acute Lymphoblastic Leukemia With Oncogenetic Features.
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Relapsed/Refractory Acute Lymphoblastic Leukemia
T-cell Acute Lymphoblastic Leukemia
Lead sponsor: Versailles Hospital
Sponsor class: OTHER
First posted: 2023-04-27
Enrollment: 80
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: OTHER
Sampling method: PROBABILITY_SAMPLE
Study population: Patients 18 years of age or older, with relapsed or refractory T cell precursor-ALL or T-cell Lymphoblastic lymphoma, with oncogenetic analysis performed at diagnosis and/or relapse in the central laboratory.

Brief summary: In order to improve the outcome of relapsed and/or refractory T-cell precursor acute lymphoblastic leukemia (T-ALL) patients, and to facilitate the use of oncogenetic targeted therapies in these patients, we set up an observational cohort, collecting clinical and biological information's from patients with T-ALL in relapse or refractory, as well as the use or not of a targeted therapy. The analysis of the cohort will allow us to evaluate the impact of this therapeutic strategies on the patients' fate, and to facilitate access to innovation and personalized medicine for these patients.

Detailed description: Depending on protocol and leukemia subtype, 5-10% of T-ALL patients are primary refractory, and 30-40% of patients will relapse. A new complete remission is attained in 20-40% of patients, but prolonged disease-free survival is observed in only 10-15% of cases. Nelarabine is approved for R/R T-ALL in second relapses, with a CR rate of 36% in the registration study, and an overall survival of 24% at 1 year and 12% at 3 years.

The biological landscape of T-ALL is well characterized, with the identification of at least 10 key recurrently mutated pathways including transcriptional regulation (91% of cases), cell cycle regulation and tumor suppression (84%), NOTCH1 signaling (79%), epigenetic regulation (68%), PI3K-AKT-mTOR signaling (29%), JAK/STAT signaling (25%), RAS signaling (14%), ribosomal function (13%), ubiquitination (9%) and RNA processing (9%). Furthermore, T-ALL cells are dependent upon BCL-XL and upon BCL-2, especially when the T-ALL blasts bear an ETP phenotype. However, genomic data cannot reliably predict the response of leukemic cells to a given treatment, due to interactions of the different cellular pathways affected in a living leukemic cell. Therefore, the combination of genotypic and phenotypic data may overcome this problem.

In France, patients with relapsed or refractory T-ALL (and also T-cell lymphoblastic lymphomas) are already proposed to undergo a genotypic (oncogenetic characterization) and a phenotypic (drug testing assay) characterization as a standard of care procedure. Based on the results obtained in fresh leukemic cells, a national scientific committee may recommend the used of targeted drugs alone or in combination, in the context of a "off-label" or a "compassionate" use (for example : Temsirolimus + Erwiniase + Venetoclax in PI3K-AKT-mTOR mutated ALL / Tofacitinib + Venetoclax in IL7R-JAK-STAT mutated ALL / 5-azacytidine + Venetocax in hypermethylated ALL / ...).

All patients who undergone this procedure will be proposed to be registered in the ALL-Target registry (ALL-target Observatory). After registration, data related to disease history, disease characterization and disease treatment as well as data describing the patient's condition will be collected.

Some patients may receive conventional chemotherapy as a salvage (conventional cohort), others may receive targeted therapy as a salvage (personalized medicine cohort). The aim of the registry is to evaluate the benefit of each treatment strategy in term of response as a primary end point. Comparison between the two cohorts will be performed after adjustment for confounding factors. Results of subgroups will also be reported using descriptive statistics. Secondary endpoints will include safety of the treatment strategy, survival, disease free survival and progression free survival.

Eligibility criteria: Inclusion Criteria:

* Patients 18 years of age or older
* Patients with relapsed or refractory T-cell precursor ALL or T-cell lymphoblastic lymphoma
* Oncogenetic analysis performed at diagnosis and/or relapse in the central laboratory

Exclusion Criteria:

* Patient who refuse to be registered

Primary outcomes:
measure: Response rate defined as complete remission and remission without complete hematological recovery (CR + CRi).
timeFrame: 3 months
Secondary outcomes:
measure: Performance Status of patients
timeFrame: 3 months
measure: Biological description of T-ALL
timeFrame: 3 months
measure: Description of the treatments received
timeFrame: 3 months
measure: Description of Overall response rate to treatment
timeFrame: 2 years
measure: Description of the relapse rate
timeFrame: 2 years
measure: Description of survival rate
timeFrame: 2 years
measure: Duration of response
timeFrame: 2 years
measure: Description of Adverse Events
timeFrame: 2 years
Other outcomes:
Locations:
city: Amiens
country: France
facility: CHU Amiens Picardie
city: Angers
country: France
facility: Chu Angers
city: Annecy
country: France
facility: CH Annecy Genevois
city: Argenteuil
country: France
facility: Centre Hospitalier d'Argenteuil
city: Avignon
country: France
facility: Centre Hospitalier Montfavet Avignon
city: Bayonne
country: France
facility: Centre Hospitalier de la Cote Basque
city: Bobigny
country: France
facility: Hopital Avicenne
city: Bordeaux
country: France
facility: CHU de Bordeaux
city: Caen
country: France
facility: Centre Hospitalier Universitaire de CAEN
city: Clermont-Ferrand
country: France
facility: CHU Clermont Ferrand
city: Corbeil-Essonnes
country: France
facility: Centre Hospitalier Sud Francilien
city: Créteil
country: France
facility: Hopital Henri Mondor
city: Dijon
country: France
facility: CHU Dijon Bourgogne
city: Lille
country: France
facility: CHU Lille
city: Limoges
country: France
facility: Chu Limoges
city: Lyon
country: France
facility: Hospices Civiles de Lyon
city: Meaux
country: France
facility: Grand Hopital de l'Est Francilien
city: Montpellier
country: France
facility: CHU de Montpellier
city: Mulhouse
country: France
facility: Centre Hospitalier Emile Muller de Mulhouse
city: Nancy
country: France
facility: CHU Nancy
city: Nice
country: France
facility: Centre anti-cancer Nice : Antoine Lacassagne
city: Nice
country: France
facility: CHU de Nice
city: Nîmes
country: France
facility: CHU Nîmes
city: Paris
country: France
facility: Hopital Saint-Antoine
city: Paris
country: France
facility: Hôpital Cochin
city: Perpignan
country: France
facility: Centre Hospitalier de Perpignan
city: Rennes
country: France
facility: CHU de Rennes
city: Saint-Étienne
country: France
facility: CHU Centre Hospitalier Universitaire de Saint-Étienne - Loire
city: Toulouse
country: France
facility: ONCOPOLE
city: Versailles
country: France
facility: Centre Hospitalier de Versailles
city: Villejuif
country: France
facility: Institut Gustave Roussy
Study officials:
References: