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Acute Myeloid LeukemiaDREAMNCT06225128

Dynamics of Resistance Emergence to Azacitidine-based Therapies in Acute Myeloid Leukemia

An observational study of Acute Myeloid Leukemia, run by Assistance Publique - Hôpitaux de Paris at 1 site in France.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
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Trial summary

Acute myeloid leukemia (AML) is a malignancy of aging endowed with poor prognosis. The combination of the hypomethylating agent azacitidine (AZA) with the BCL-2 inhibitor venetoclax (VEN) is the first-line treatment of older AML patients but is endowed with substantial resistance. Read more about this study

Who is it for?
Ages 18 to 100 years
Conditions the study is for
Acute Myeloid Leukemia
What is being tested?
Biobanking blood and Bone marrow specimens
How many people
120 participants
Where
1 siteFrance
Study dates
16 Jan 2024to 19 Jun 2027
Phase
Observational
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 100 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Study population: Patients already included in eTHEMA observationnal cohort

Who may be able to join

  • be ≥18 years old,
  • have a newly diagnosed AML according to ICC 2022 criteria,
  • patients with AML related to prior chemotherapy or radiotherapy for another cancer will be eligible,
  • patients with MDS/AML per ICC 2022 criteria will be eligible,
  • have signed the informed consent form of the eTHEMA observatory trial
  • have ≥10% blasts on the bone marrow smear at screening,
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  • have not received any treatment for AML except for hydroxyurea and/or steroids,
  • Patients having previously received hypomethylating agents for an antecedent myelodysplastic syndrome are ineligible,
  • be eligible to AZA/VEN or AZA/IVO therapy, due to general health status,
  • have an ECOG performance status ≤ 2,
  • be planned to receive azacitidine and venetoclax (AZA/VEN) or azacitidine and ivosidenib (AZA/IVO) as frontline therapy,
  • weigh ≥ 40 kg (compliance to Loi Jardé for PB sampling),
  • have provided written informed consent obtained prior to any screening procedures

Who cannot join

  • At screening, patients must NOT:
  • have suspected or proven acute promyelocytic leukemia based on morphology, karyotype or molecular assay, including APL with non-PML::RARA rearrangements,
  • have suspected or proven AML with t(9;22)(q34.1;q11.2)/BCR::ABL1 based on karyotype or molecular assay,
  • have myeloid sarcoma,
  • have failed to perform bone marrow aspiration at screening,
  • have received previous therapy for AML with any investigational agent or cytotoxic drug, within 28 days before starting treatment. Only hydroxyurea is permitted for the control of blood counts. Aside from hypomethylating agents, other treatments for an antecedent myeloid neoplasm (MDS or MPN) are not considered as exclusion criteria,
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  • be pregnant or breastfeeding (for women),
  • present any of concurrent severe and/or uncontrolled medical condition, which could compromise participation in the study,
  • be enrolled in a clinical trial which could compromise participation in the study.

Trial locations and contacts

1 site in 1 country. Contact the study team or a site near you to ask about taking part.

Raphael Itzykson, Pr contact

+33142499643

raphael.itzykson@aphp.fr

Jérôme Lambert, Pr contact

+33142499742

jerome.lambert@u-paris.fr

France1 site, 1 recruiting

  • Hôpital Saint Louis

    Paris

    Raphael Itzykson, Pr, 142499643 ext. +33, raphael.itzykson@aphp.fr

    Recruiting

Other trials in France

About this study

Official title: Dynamics of Resistance Emergence to Azacitidine-based Therapies in Acute Myeloid

Acute myeloid leukemia (AML) is a malignancy of aging endowed with poor prognosis. The combination of the hypomethylating agent azacitidine (AZA) with the BCL-2 inhibitor venetoclax (VEN) is the first-line treatment of older AML patients but is endowed with substantial resistance. The project leverages functional precision oncology, single-cell studies and mouse experiments to dissect the mechanisms of primary and adaptive resistance to AZA/VEN. The primary objective is to prospectively validate an ex vivo drug sensitivity testing (DST) assay as predictor of primary resistance to first-line AZA/VEN in 100 unfit AML patients. The study will also explore whether newer DST assays with enhanced niche mimicry can improve on the standard assay.

By serially interrogating the short-term fate of both leukemic and immune cells upon AZA/VEN exposure in patients primed towards refractoriness, transient or prolonged remission, the aim is to dissect the cell-intrinsic and immune-mediated mechanisms of primary versus adaptive resistance. A parallel flow cytometry study will interrogate the role of senescence in AZA/VEN activity. These translational studies will be mirrored by experiments in a transplantable AML model derived from syngeneic mice harboring the age-related Tet2-/- leukemia-predisposing genotype. Lineage tracing single-cell experiments will backtrack AZA/VEN resistance to determine whether it is driven by selection or adaptation. The actionable stress sensor Pml will be invalidated in the same model to determine whether Pml-driven senescence contributes to AZA/VEN anti-leukemic activity in vivo. The project will pave the way to the clinical implementation of functional precision oncology in a high-risk malignancy. By simultaneously interrogating cell-intrinsic and immune-mediated drug resistance in vivo in a prospective patient cohort mirrored by controlled mice experiments, the project will provide a framework for the integrative analysis of drug resistance in cancers.

Being tested
Biobanking blood, Bone marrow specimens
Medical subject headings
Leukemia, Myeloid, Acute

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Biobanking bloodOther

    Additional volume of 30mL (EDTA) At Screening, pre-Cycle 1 Day 1,Day 1 H8, Day 2, Day of post-cycle 1 and post-cycle 6 evaluation.

  • Bone marrow specimensOther

    Additional volume of 2mL (EDTA)

    • at screening for correlative studies,at Day 7 for smears and for correlative studies.
    • Post-cycle 1 and post-cycle 6 evaluations for correlative studies.

    Optionnal :

    Trephine biopsy at screening and at post-cycle 1 and 6 evaluations (performed at the same time as aspiration)

Study groups in NCT06225128
Study groupRoleWhat they receive
Patients with AMLNot described
Receives: Other: Biobanking blood; Other: Bone marrow specimens

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Overall Response (CR+CRh+Cri)

    Overall Response (CR+CRh+Cri) per European LeukemiaNet 2022 criteria (Döhner et al., Blood 2022), according to DST on the NEXT platform on the population treated per protocol (AZA/VEN).

    Measured: Up to 6 months

Secondary outcomes (9)

  1. Number of MRD-negative response (including CRMRD-, CRhMRD- and CRiMRD-)

    Measured: Up to 6 months

  2. Best response after any number of AZA/VEN cycles

    It is ranked as follow : CR > CRh > Cri

    Measured: Up to 6 months

  3. MRD-negative response after any number of AZA/VEN cycles

    including CRMRD-, CRhMRD- and CriMRD-

    Measured: Up to 6 months

  4. Response duration

    Defined as the interval between first response among CR, CRh and Cri

    Measured: Up to 6 months

  5. Treatment failure per ELN22 criteria

    Measured: Up to 6 months

  6. Overall survival

    Measured: Up to 6 months

  7. Event-free survival

    Measured: Up to 6 months

  8. Relapse-free survival

    Measured: Up to 6 months

  9. Cumulative Incidence of Relapse (CIR) according to DST on the NEXT platform

    Measured: Up to 6 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted25 Jan 2024
  2. Study start16 Jan 2024
  3. Primary completion19 Jun 2027 (estimated)
  4. Study completion19 Jun 2027 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Observational
Observational model
Cohort
Time perspective
Prospective
Enrolment
120 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT06225128
Sponsor's protocol ID
APHP230805
Acronym
DREAM
Status last verified
Jul 2023
First submitted
12 Dec 2023
Last updated
29 May 2024
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
Undecided

Questions about this trial

What is this clinical trial studying?

An observational study of Acute Myeloid Leukemia, run by Assistance Publique - Hôpitaux de Paris at 1 site in France.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 13 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: looking for participants now, as of the sponsor's last update on 29 May 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in France. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Raphael Itzykson, Pr (+33142499643, raphael.itzykson@aphp.fr), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Overall Response (CR+CRh+Cri) (time frame: Up to 6 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT06225128.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 May 2024.

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