Single-cell Dynamic Profiling in Adults With Newly Diagnosed Acute Myeloid Leukemia Treated With Intensive Chemotherapy. A THEMA Study"

NCT ID: NCT05304156

Last Updated: 2024-05-29

Basic Information

• Recruitment Status: RECRUITING
• Total Enrollment: 200 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2022-04-26
• Study Completion Date: 2026-05-26

Brief Summary

The detailed molecular and cellular mechanisms underpinning the clinical activity of most chemotherapies in cancers remain incompletely understood. Understanding how these drugs really act is a prerequisite for their rational therapeutic optimization.

Recent observations suggest that early molecular and cellular changes in cancer cells upon chemotherapy exposure may dictate their long-term fate.

We aim to address this question in previously untreated adult Acute Myeloid Leukemia (AML) patients treated with anthracycline/cytarabine association (either as free drugs, '7+3' regimen, or in liposomal formulation, CPX-351) by sequentially sampling peripheral blood during the first course of therapy, and by performing an early bone marrow reassessment. We will apply single cell RNA sequencing and multiparameter flow cytometry to correlate dynamic phenotypic landscapes with clinical outcomes (remission achievement and relapse-free survival).

The study will be carried in two phases. First, a feasibility phase will be carried in the first 20 patients irrespective of the genetic make-up of their leukemic cells to identify the optimal pre-analytical conditions for single-cell transcriptional profiling.

Second, an expansion phase will be carried focusing on two genetically subsets of patients chosen on the basis of their relative abundance and variability of clinical outcome, namely NPM1c-mutated AML (30% of patients, 60% cure rate) and NPM1-wildtype intermediate-risk AML (25% of patients, 40% cure rate), to correlate single-cell fates with remission and with long-term remission-free survival.

Conditions

Acute Myeloid Leukemia

Study Design

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

Study Groups

Standard of Care in patients with AML

Standard of Care including a first course containing one of the following backbones without addition of third agent before day 8 of induction (approved drugs such as midostaurine or investigational agents administered beyond day 8 are allowed) :

• 7+3 induction 3+7 with daunorubicin (or idarubicin) and cytarabine
• CPX-351 induction

Biobanking blood and bone marrow specimens

Intervention Type: OTHER

Interventions, procedures added for research purposes :

Blood Samples :

• Peripheral blood (20mL EDTA) (at Screening, pre-ICT Day 1, Day1 H8, Day 2, Day 3, Day 4 and Day of EOI evaluation

Bone Marrow samples :

• Biopsy at Screening and at EOI Evaluation
• Additional volume (2mL EDTA) on the Screening,2 and EOI Evaluation aspirations for single-cell analyses.
• Aspiration at D8 for Smears and 2 mL EDTA for single-cell analyses (instead of D15 standard care).

Interventions

Biobanking blood and bone marrow specimens

Interventions, procedures added for research purposes :

Blood Samples :

• Peripheral blood (20mL EDTA) (at Screening, pre-ICT Day 1, Day1 H8, Day 2, Day 3, Day 4 and Day of EOI evaluation

Bone Marrow samples :

• Biopsy at Screening and at EOI Evaluation
• Additional volume (2mL EDTA) on the Screening,2 and EOI Evaluation aspirations for single-cell analyses.
• Aspiration at D8 for Smears and 2 mL EDTA for single-cell analyses (instead of D15 standard care).

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

• aged ≥18 years old,
• have a newly diagnosed AML according to WHO criteria

o patients with AML related to prior chemotherapy or radiotherapy for another cancer will be eligible,

• have signed the informed consent form of the e-THEMA observatory trial
• have ≥10% blasts (blasts+myeloblasts) on the peripheral blood smear at screening,
• have ≥20% blasts on the bone marrow smear at screening,
• have not received any treatment for AML except for hydroxyurea and/or 6-mercaptopurine and steroids

o Patients having previous treatments for antecedent myeloid neoplasms including hypomethylating agents remain eligible,

• Eligible to intensive chemotherapy, due to general health status,
• ECOG performance status ≤ 2,
• Patient is planned to receive anthracycline (daunorubicin [DNR] or idarubicine [IDA]) - cytarabine 7+3 with or without gemtuzumab ozogamycin (GO) or midostaurine, or CPX-351 as first induction course,
• Weighing 50 kg or more (compliance to Loi Jardé for PB sampling),
• Written informed consent obtained prior to any screening procedures,
• Eligible for National Health Insurance in France.

Exclusion Criteria

• Suspected or proven acute promyelocytic leukemia based on morphology, karyotype or molecular assay,
• Failure to perform bone marrow aspiration at diagnosis,
• Unstable angina, New York Heart Association (NYHA) class 3 or 4 congestive heart failure,
• Prior anthracycline exposure more than 360 mg/m²,
• Women who are pregnant or breastfeeding.
• Any of concurrent severe and/or uncontrolled medical condition, which could compromise participation in the study.
• Enrolment in a clinical trial which could compromise participation in the study.

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

Sponsors

Assistance Publique - Hôpitaux de Paris

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Hôpital Avicenne

Bobigny, , France

Site Status: RECRUITING

Hôpital Saint Louis

Paris, , France

Site Status: RECRUITING

Countries

France

Central Contacts

Raphael ITZYKSON

Role: CONTACT

raphael.itzykson@aphp.fr

+33171207031

Matthieu Resche-Rigon

Role: CONTACT

matthieu.resche-rigon@u-paris.fr

+33142499742

Facility Contacts

Thorsten Braun, Pr

Role: primary

Raphael Itzykson, Pr

Role: primary

raphael.itzykson@aphp.fr

Other Identifiers

APHP 211175

Identifier Type: -

Identifier Source: org_study_id