AzTrials
AzTrials

Acute Myeloid LeukemiaPhase 2NCT04867928

Venetoclax and Azacitidine for the Management of Molecular Relapse/Progression in Adult NPM1-mutated Acute Myeloid Leukemia

A Phase 2 study testing Venetoclax+azacitidine in people with Acute Myeloid Leukemia and Acute Myeloid Leukemia, in Relapse, run by Gruppo Italiano Malattie EMatologiche dell'Adulto at 1 site in Italy.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Official record
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Trial summary

This is a phase 2, non-randomized, interventional, open-label, multicenter trial evaluating the efficacy of VEN-AZA as a bridge-to-transplant therapy in chemotherapy-treated adult NPM1mut AML patients who experience molecular relapse or progression during treatment or follow-up. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Venetoclax+azacitidine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
35 participants
Where
1 siteItaly
Study dates
1 Mar 2022to Jan 2025
Phase
Phase 2
Are there results?
None posted in the registry

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 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Subject must be ≥ 18 years of age
  • Subject must have received previous diagnosis of NPM1mut AML with or without concomitant FLT3-TKD or FLT3-ITD
  • At screening, subject must have confirmed NPM1 type A, B, or D mutant transcripts
  • Subject must be eligible for alloSCT, according to transplant center policy
  • Subject must have undergone at least two cycles of conventional anthracycline- and cytarabine-based chemotherapy, achieving first CR (CR1)
  • Subject must be in morphological CR1 with bone marrow detectable minimal residual disease (MRD) positivity, defined as qRT-PCR NPM1 transcript ≥ 0.01/100 ABL1 copies and confirmed in two consecutive determinations performed at 2 to 4 weeks' distance
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  • Molecular progression is defined in patients with molecular persistence at low copy number as an increase of MRD copy number ≥ 1 log10 between 2 positive samples.
  • Molecular relapse is defined in patients previously tested MRD negative as an increase in MRD copy number ≥ 1 log10 between 2 positive samples
  • Subject must have a projected life expectancy of at least 12 weeks.
  • Subject must have an Eastern Cooperative Oncology Group (ECOG) Performance status < 2
  • Subject must have adequate renal and hepatic function per local laboratory reference range as follows:
  • Aspartate transaminase (AST) and alanine transaminase (ALT) < 3.0X ULN
  • Bilirubin ≤1.5 x ULN (unless bilirubin rise is due to Gilbert's syndrome or of non-hepatic origin)
  • Subject must have adequate renal function as demonstrated by a creatinine clearance ≥ 30 mL/min; calculated by the Cockcroft Gault formula or measured by 24 hours' urine collection.
  • Female subjects of childbearing potential must have negative results for pregnancy test at screening
  • Female and male patients who are fertile must agree to use an effective form of contraception with their sexual partners from screening through 3 months after the end of treatment.
  • Signed written informed consent according to ICH/EU/GCP and national local laws.

Who cannot join

  • Subject has acute promyelocytic leukemia (APL)
  • Subject has known active CNS involvement with AML
  • Subject has received previous treatment with venetoclax and/or hypomethylating agents
  • Subject has undergone alloSCT for AML
  • Subject has more than 5% of bone marrow blast cells at screening bone marrow aspirate
  • Subject is known to be positive for HIV
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  • Evidence of other clinically significant uncontrolled condition(s) including, but not limited to:
  • Uncontrolled and/or active systemic infection (viral, bacterial or fungal)
  • Chronic hepatitis B virus (HBV) or hepatitis C (HCV) requiring treatment. Note: subjects with serologic evidence of prior vaccination to HBV (i.e. hepatitis B surface (HBs) antigen negative-, anti-HBs antibody positive and anti-hepatitis B core (HBc) antibody negative) or positive anti-HBc antibody from intravenous immunoglobulins (IVIG) may participate.
  • Cardiac history of CHF requiring treatment or Ejection Fraction ≤ 50% or chronic stable angina;
  • DLCO ≤ 65% or FEV1 ≤ 65%;
  • Creatinine clearance < 30 ml/min
  • Subject has a cardiovascular disability status of New York Heart Association Class > 2
  • Class 2 is i. defined as cardiac disease in which patients are comfortable at rest but ordinary physical activity ii. results in fatigue, palpitations, dyspnea, or anginal pain
  • Patients who are pregnant or breast feeding and adults of reproductive potential not employing an effective method of birth control (women of childbearing potential must have a negative serum pregnancy test within 48 hrs prior to administration of induction therapy). Post-menopausal women must be amenorrhoic for at least 12 months to be considered of non-child bearing potential. Male and female patients must agree to employ an effective barrier method of birth control throughout the study and for up to 3 months following discontinuation of study drugs.
  • Patients unwilling or unable to comply with the protocol.

Trial locations and contacts

1 site in 1 country.

Paola Fazi contact

0670390526

p.fazi@gimema.it

Enrico Crea contact

0670390514

e.crea@gimema.it

Italy1 site, 1 recruiting

  • EMATOLOGIA- AOU Policlinico S.Orsola

    Bologna

    Antonio Curti

    Recruiting

Other trials in Italy

About this study

Official title: A Multicentric Phase 2 Study of Venetoclax and Azacitidine for the Management of Molecular Relapse/Progression in Adult NPM1-MUTATED Acute Myeloid Leukemia

This is a phase 2, non-randomized, interventional, open-label, multicenter trial evaluating the efficacy of VEN-AZA as a bridge-to-transplant therapy in chemotherapy-treated adult NPM1mut AML patients who experience molecular relapse or progression during treatment or follow-up. Subjects will receive cycles of venetoclax plus azacitidine. After each cycle, MRD will be evaluated and at any time of MRD-negativity, AlloSCT will be performed.

Read the detailed description

This is a phase 2, non-randomized, interventional, open-label, multicenter trial evaluating the efficacy of VEN-AZA as a bridge-to-transplant therapy in chemotherapy-treated adult NPM1mut AML patients who experience molecular relapse or progression during treatment or follow-up.

Subjects will receive venetoclax 400 mg orally QD on Days 1 - 28 plus azacitidine 75 mg/m2 SC or IV daily for 7 days. Cycle Length: 28 Days.

Subjects will continue treatment until subsequent alloSCT, documented morphological bone marrow and/or extramedullary disease progression, toxicity, withdrawal of consent, or the subject meets other protocol criteria for discontinuation (whichever occurs first).

After each cycle, MRD will be evaluated. AlloSCT is recommended at any time of MRD-negativity. After 6 cycles of treatment, regardless MRD status, patients will proceed to alloSCT.

Being tested
Venetoclax+azacitidine
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.

  • Venetoclax+azacitidineDrug

    subjects will receive venetoclax 400 mg orally QD on Days 1 - 28 plus azacitidine 75 mg/m2 SC or IV daily for 7 days. Cycle Length - 28 Days. . Subjects will continue treatment until subsequent alloSCT.

Study groups in NCT04867928
Study groupRoleWhat they receive
Venetoclax+azacitidineExperimentalsubjects will receive treatment until alloSCT
Receives: Drug: Venetoclax+azacitidine

What is being measured

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

  1. Treatment efficacy in terms of relapse rate

    Evaluation of treatment efficacy in terms of percentage of patients who do not experience overt relapse at 6 months or within stem cell transplant.

    Measured: at 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 posted30 Apr 2021
  2. Study start1 Mar 2022
  3. Primary completionJan 2025 (estimated)
  4. Study completionJan 2025 (estimated)

Resources

More details

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

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
35 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04867928
Sponsor's protocol ID
AML2521
Status last verified
Mar 2022
First submitted
28 Apr 2021
Last updated
16 Mar 2022
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No

Publications

  • Sartor C, Brunetti L, Audisio E, Cignetti A, Zannoni L, Cristiano G, Nanni J, Ciruolo R, Zingarelli F, Ottaviani E, Patuelli A, Bandini L, Forte D, Sciabolacci S, Cardinali V, Papayannidis C, Cavo M, Martelli MP, Curti A. A venetoclax and azacitidine bridge-to-transplant strategy for NPM1-mutated acute myeloid leukaemia in molecular failure. Br J Haematol. 2023 Aug;202(3):599-607. doi: 10.1111/bjh.18887. Epub 2023 May 24.

    PubMed 37226312

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Venetoclax+azacitidine in people with Acute Myeloid Leukemia and Acute Myeloid Leukemia, in Relapse, run by Gruppo Italiano Malattie EMatologiche dell'Adulto at 1 site in Italy.

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 17 inclusion and 16 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: status not confirmed, as of the sponsor's last update on 16 Mar 2022. 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 Italy. 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.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Results are not available in the source record.

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

Contact Paola Fazi (0670390526, p.fazi@gimema.it), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Treatment efficacy in terms of relapse rate (time frame: at 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 NCT04867928, which also lists 1 linked publication.

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 16 Mar 2022.

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