A Precision Medicine Randomized Trial for Patients with Relapsed or Refractory T-Cell Acute Lymphoblastic Leukemia Based on a Functional Approach. All-Target Trial

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Centre Hospitalier De Versailles

Participant type

Pediatric, Patients

Age range

0-17 years, 18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Hemic and Lymphatic Diseases [C15]

Decision date (initial)

2026-06-01

Transition trial

No

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

No

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Therapy

Evaluer le bénéfice d’une stratégie basée sur la médecine de précision (combinaisons de traitements ciblés (CTC)) sur le taux de réponse hématologique chez des patients atteints de leucémie aiguë lymphoblastique T en rechute ou réfractaire.

Secondary objectives 5

1. 1. To assess the benefit and tolerance of the TTOs, overall and for each TTO.
2. 2. To evaluate overall survival, relapse free survival and event free survival.
3. 3. To compare the quality of life and patient related outcomes (QOL, PROM) across the strategies and across the specific TTOs.
4. 4. To explore the mechanisms of relapse.
5. 5. To analyze the allocation of TTOs

Conditions and MedDRA coding

Relapsed/refractory T-cell Acute Lymphoblastic Leukemia

Regulatory references

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 8

1. Patients aged 15y or more (under 18y only for France)
2. Signed informed consent for patients aged ≥ 18 years and signed informed consent from both parents for patients aged between ≥ 15 years and < 18 years (only for France).
3. Patients with T-cell acute lymphoblastic leukemia in first or second relapse or in the refractory phase. a) Patients with first relapses are eligible if relapse occurred within 24 months post complete remission achievement and if nelarabine is not considered as appropriate salvage therapy. b) Patients with second and all subsequent relapses are eligible. c) Refractory patients are defined as patients not responding after at least 2 lines of chemotherapy (induction + salvage). d) Patients with relapses post-transplant and post CART-cells treatments are eligible.
4. Blast cells in blood and/or bone marrow to allow the shipment to one of the 3 reference laboratories in France, Spain and The Netherlands or An informative biological assessment already performed within 10 days prior to inclusion in one of the three reference laboratories in France, Spain or The Netherlands with at least one targeted therapeutic option validated (TTO1, venetoclax + tofacitinib; TTO2, venetoclax+ everolimus + enrylaze; TTO3, venetoclax + 5-azacytidine) by one of the three National Validation Committees.
5. Adequate ECOG score (0-3).
6. Patients must be affiliated to a National Health systems (see country-based specificity).
7. Patients must not have a contra-indication for venetoclax, tofacitinib, everolimus, glutaminolytic agents (enrylaze) or 5-azacytidine.
8. Willingness of women of child-bearing potential (WOCBP) or of male patients whose sexual partners are WOCBP to use an effective form of contraception during the study and at least 3 months thereafter (see Annex 13.9).

Exclusion criteria 11

1. Patients in palliative care.
2. Patients with late relapses after the first complete remission (> 24 months post complete remission).
3. Patients with extramedullary only relapses or with clinically symptomatic central nervous system (CNS) involvement.
4. Pregnant or lactating women.
5. Participation in another clinical trial with an investigative drug at the time of study enrolment.
6. Individuals with another active uncontrolled malignancy.
7. Known active HBV-, HCV and HIV related diseases.
8. Patient under curatorship or deprived of liberty (except for minors).
9. Patients with contra-indication to chemotherapy except if considered related to the ALL: • ASAT (SGOT) and/or ALAT (SGPT) > 5 x ULN • Total bilirubin ≥ 2.5 x ULN • Estimated glomerular filtration rate (GFR) < 50 mL/mn using the MDRD equation
10. Administration of live or live-attenuated vaccines within 4 weeks prior to the first dose of study treatment (see Annex 13.10)
11. Subject presenting with psychiatric disorders or any other condition that impair their ability to cooperate with study procedures.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Hematological remission rate, which is a composite outcome (CRc), defined as the best response observed within 3 months post randomization, either complete remission (CR) or remission without complete hematological recovery (CRi).

Secondary endpoints 13

1. 1. Hematological response rate (HR) defined as complete remission (CR), remission without complete hematological recovery (CRi) and partial response (PR) by 3 months post randomization.
2. 2. Overall survival, defined as the time from randomization up to death, whatever the cause
3. 3. Stable disease by 3 months
4. 4. Duration of response
5. 5. Event free survival, defined as the time from randomization up to relapse or death, whichever occurred first
6. 6. Relapse free survival, defined as the time from response up to relapse or death
7. 7. Adverse events and cumulative incidence of adverse events (treatment duration + 1 mois)
8. 8. Response per treatment combination by 3 and 6 months
9. 9. Bridge to transplant, bridge to CART-cell
10. 10. Minimal residual disease at 3 months in responding patients
11. 11. Quality of life (HM-PRO & HADS) questionnaires monthly up to 3 months
12. 12. Mechanisms of resistance to therapies
13. 13. Post-hoc analysis of TTO allocation

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 7

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Centre Hospitalier De Versailles

Sponsor organisation

Centre Hospitalier De Versailles

Address

177 Rue De Versailles, Le Chesnay Le Chesnay

City

Le Chesnay Rocquencourt

Postcode

78150

Country

France

Scientific contact point

Organisation

Centre Hospitalier De Versailles

Contact name

ROUSSELOT Philippe

Public contact point

Organisation

Centre Hospitalier De Versailles

Contact name

FORT Mélody

Locations

5 EU/EEA countries · 68 investigational sites

By country

Investigational sites

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 50 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

1 submissions — initial application plus substantial / non-substantial modifications