Registry of Relapsed/Refractory T-cell Acute Lymphoblastic Leukemia

T-cell Acute Lymphoblastic Leukemia Clinical Trial

— ALLTARGETOBS  

Official title:

Observatory for Patients Treated for Relapsed or Refractory T-cell Acute Lymphoblastic Leukemia With Oncogenetic Features.

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05832125
• Other study ID #: P21/01_ALL TARGET OBS
• Status: Recruiting
• Start date: December 14, 2021
• Est. completion date: March 2024

Study information

• Verified date: April 2023
• Source: Versailles Hospital
• Contact: Aurélie CABANNES-HAMY
• Phone: +33139638909
• Email: acabannes[@]ght78sud.fr
• Is FDA regulated: No
• Study type: Observational [Patient Registry]

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 80
• Est. completion date: March 2024
• Est. primary completion date: December 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Leukemia
• Leukemia, Lymphoid
• Precursor Cell Lymphoblastic Leukemia-Lymphoma
• Precursor T-Cell Lymphoblastic Leukemia-Lymphoma
• Relapsed/Refractory Acute Lymphoblastic Leukemia
• T-cell Acute Lymphoblastic Leukemia

Locations

Country	Name	City	State
France	CHU Amiens Picardie	Amiens
France	Chu Angers	Angers
France	CH Annecy Genevois	Annecy
France	Centre Hospitalier d'Argenteuil	Argenteuil
France	Centre Hospitalier Montfavet Avignon	Avignon
France	Centre Hospitalier de la Cote Basque	Bayonne
France	Hopital Avicenne	Bobigny
France	CHU de Bordeaux	Bordeaux
France	Centre Hospitalier Universitaire de CAEN	Caen
France	CHU Clermont Ferrand	Clermont-Ferrand
France	Centre Hospitalier Sud Francilien	Corbeil-Essonnes
France	Hopital Henri Mondor	Créteil
France	CHU Dijon Bourgogne	Dijon
France	CHU Lille	Lille
France	Chu Limoges	Limoges
France	Hospices Civiles de Lyon	Lyon
France	Grand Hopital de l'Est Francilien	Meaux
France	CHU de Montpellier	Montpellier
France	Centre Hospitalier Emile Muller de Mulhouse	Mulhouse
France	CHU Nancy	Nancy
France	Centre anti-cancer Nice : Antoine Lacassagne	Nice
France	CHU de Nice	Nice
France	CHU Nîmes	Nîmes
France	Hôpital Cochin	Paris
France	Hopital Saint-Antoine	Paris
France	Centre Hospitalier de Perpignan	Perpignan
France	CHU de Rennes	Rennes
France	CHU Centre Hospitalier Universitaire de Saint-Étienne - Loire	Saint-Étienne
France	ONCOPOLE	Toulouse
France	Centre Hospitalier de Versailles	Versailles
France	Institut Gustave Roussy	Villejuif

Sponsors (1)

Lead Sponsor	Collaborator
Versailles Hospital

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Response rate defined as complete remission and remission without complete hematological recovery (CR + CRi).	Response rate defined as complete remission and remission without complete hematological recovery (CR + CRi).	3 months
Secondary	Performance Status of patients	Eastern Cooperative Oncology Group (ECOG) - Performans Status Scale PS 0 : Fully active, able to carry on all pre-disease performance without restriction PS 4: Completely disabled; cannot carry on any selfcare; totally confined to bed or chair	3 months
Secondary	Biological description of T-ALL	Phenotypic and oncogenetic characterization with mutated signaling pathways	3 months
Secondary	Description of the treatments received	Number and type of treatment lines received, including current treatment	3 months
Secondary	Description of Overall response rate to treatment	Overall response rate defined by partial response rate + complete response rate	2 years
Secondary	Description of the relapse rate	Event of relapse	2 years
Secondary	Description of survival rate	Death	2 years
Secondary	Duration of response	Response	2 years
Secondary	Description of Adverse Events	Adverse Events	2 years