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Acute Myeloid LeukemiaPhase 3Q-SOCNCT04676243

Daunorubicin or Idarubicin With Cytarabine Plus Quizartinib vs Physician's Choice in Newly Diagnosed FLT3-ITD+ AML

A Phase 3 study testing Quizartinib and Treatment according to Physician's Choice in people with Acute Myeloid Leukemia, run by University Hospital Heidelberg.

Withdrawn

Withdrawn. The study stopped before anyone enrolled.

Official record
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Trial summary

The orally administered second-generation bis-aryl urea tyrosine kinase inhibitor quizartinib is very specific for FLT3, has a high capacity for sustained FLT3-inhibition and an acceptable toxicity profile. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Acute Myeloid Leukemia
What is being tested?
Quizartinib and Treatment according to Physician's Choice
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
0 participants
Where
No sites listed yet
Study dates
May 2022to Dec 2025
Phase
Phase 3
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

  • Diagnosis of untreated acute myeloid leukemia (AML) according to the WHO 2016 definition
  • Positive for FLT3-ITD (defined as a ratio of mutant to wild-type alleles of at least 0.05; measured within 4 weeks before randomization)
  • No prior chemotherapy for leukemia except hydroxyurea to control hyperleukocytosis before randomization (≤7 days) *
  • Age ≥18 years, no upper age limit
  • ECOG PS ≤2. (Eastern Cooperative Oncology Group performance status)
  • Adequate renal function defined as creatinine clearance >50 mL/min (calculated using the standard method of the local institution)
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  • Considered eligible to receive intensive chemotherapy as per investigator judgment
  • No contraindications for FLT3-inhibitor therapy
  • No severe organ function abnormalities
  • Not included in other first-line trials
  • Non-pregnant and non-nursing women
  • Women of childbearing potential (WOCBP) must have a negative serum or urine pregnancy test with a sensitivity of at least 25 mIU/mL within 48 hours prior to randomization. ("Women of childbearing potential" is defined as a sexually active mature woman who has not undergone a hysterectomy or who has had menses at any time in the preceding 24 consecutive months).
  • WOCBP must agree to avoid getting pregnant while on therapy: WOCBP must either commit to continued abstinence from heterosexual intercourse or begin and adhere to one acceptable method of birth control (IUD, tubal ligation, or partner's vasectomy) during study and 6 months after end of study/treatment.**
  • Men must use a latex condom during any sexual contact with WOCBP, even if they have undergone a successful vasectomy and must agree to avoid to father a child during study and 6 months after end of study/treatment
  • Signed written informed consent
  • Ability of patient to understand character and consequences of the clinical trial
  • Willingness and ability to comply with scheduled visits, treatment plans, laboratory tests, and other study procedures
  • In case hyperleukocytosis is not controllable with hydroxyurea, treatment with e.g. cytarabine should be discussed in Germany with the principal investigator and in Spain with the PETHEMA trials office or for patients of both countries with the medical coordinator.
  • A high follicle-stimulating hormone (FSH) level in the postmenopausal range may be used to confirm a post-menopausal state in women not using hormonal contraception or hormonal replacement therapy at investigator's discretion.

Who cannot join

  • AML with PML-RARA or BCR-ABL1
  • Patients with known active central nervous system (CNS) leukemia (assessed clinically).
  • Isolated extramedullary manifestation of AML
  • Patients with a "currently active" second malignancy other than non-melanoma skin cancer. Patients are not considered to have a "currently active" malignancy if they have completed therapy for more than one year and are considered by their physician to be at less than 30% risk of relapse within one year.
  • Prior treatment for AML, except for the following allowances:
  • Leukapheresis;
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  • Treatment for hyperleukocytosis with hydroxyurea;
  • Cranial radiotherapy for central nervous system (CNS) leukostasis;
  • Prophylactic intrathecal chemotherapy;
  • Growth factor/cytokine support;
  • Uncontrolled or significant cardiovascular disease, including any of the following:
  • History of heart failure NYHA class 3 or 4
  • Left ventricular ejection fraction (LVEF) ≤40% by echocardiogram (ECHO)
  • History of uncontrolled angina pectoris or myocardial infarction within 12 months prior to screening
  • History of second (Mobitz II) or third degree heart block or any cardiac arrhythmias requiring anti-arrhythmic therapy (beta blockers or digoxin are permitted)
  • Inadequate liver function at screening: ALT and AST ≥2.5 x ULN), total bilirubin ≥1.5 x ULN; Alkaline phosphatase ≥2.5 x ULN. Known liver cirrhosis or history of Sinusoidal Obstruction Syndrome (SOS)
  • Known positivity for HIV, active HBV, HCV or hepatitis A infection (active hepatitis HBV defined by HBsAg positivity, active HCV defined by positive virus load)
  • Uncontrolled active infection
  • Evidence or history of severe non-leukemia associated bleeding diathesis or coagulopathy
  • Any one of the following ongoing or present in the previous 6 months: congenital long QT syndrome, Torsades de Pointes, arrhythmias (including sustained ventricular tachyarrhythmia), right or left bundle branch block and bifascicular block, unstable angina, coronary/peripheral artery bypass graft, cerebrovascular accident, transient ischemic attack or symptomatic pulmonary embolism; as well as bradycardia defined as <50 bpms
  • QTc interval at screening >450 msec using the Fredericia correction (QTcF).
  • Patients known to be refractory to platelet or packed red cell transfusions as per institutional guidelines, or who are known to refuse or who are likely to refuse blood product support.
  • Severe neurologic or psychiatric disorder interfering with ability of giving informed consent
  • Known or suspected active alcohol or drug abuse
  • No consent for registration, storage and processing of the individual disease-characteristics and course as well as informing the family physician about study participation.
  • Pregnancy and lactation
  • History of hypersensitivity to the investigational medicinal product or to any drug with similar chemical structure or to any excipient present in the pharmaceutical form of the investigational medicinal product
  • Prior treatment with quizartinib

About this study

Official title: Randomized Study in Newly Diagnosed AML With FLT3-ITD Comparing Daunorubicin/ Cytarabine or Idarubicin/Cytarabine and Quizartinib to Physician's Choice

The orally administered second-generation bis-aryl urea tyrosine kinase inhibitor quizartinib is very specific for FLT3, has a high capacity for sustained FLT3-inhibition and an acceptable toxicity profile. Furthermore, single agent quizartinib doubled the response rate as compared to standard of care in a randomized study in r/r-AML. Combination therapy of quizartinib with intensive standard induction chemotherapy has been shown to be safe and moreover, single agent quizartinib maintenance therapy is feasible even after allogeneic HCT.

The efficacy of quizartinib in combination with intensive induction and post-remission therapy including allogeneic HCT and single agent quizartinib as maintenance therapy is evaluated by this protocol. This approach is compared in a randomized manner to the current standard of care.

Read the detailed description

This is a multicenter, upfront randomized phase III trial of patients with FLT3-ITD positive AML comparing quizartinib in combination with SOC chemotherapy versus treatment according to physician's choice (PhC). Efficacy is assessed by comparing EFS between the quizartinib and the PhC arm of the study.

Primary objective To improve modified event-free survival (mEFS) with Quizartinib added to induction and consolidation therapy followed by single agent maintenance therapy compared to physician's choice (PhC)

Secondary objectives To improve overall survival (OS) with Quizartinib added to conventional therapy compared to physician's choice; To improve remission (including CR/CRi/CRh) rate with Quizartinib added to conventional therapy compared to physician's choice To reduce measurable residual disease (MRD) with Quizartinib added to conventional therapy compared to physician's choice after induction (MRDind), consolidation (MRDcons), before allogeneic hematopoietic cell transplantation (MRDpre-HCT ) and maintenance (MRDmaintenance) therapy Assessment of patient reported outcomes (PRO) after induction, consolidation and maintenance therapy and after two years Evaluation of safety based on duration of neutropenia and leukopenia, incidence of infection, duration of initial hospitalization and number of transfusions (e.g. packed red blood cells and platelets) Cost-effectiveness analysis of the two different treatment schedules from health care payer´s perspective.

Budget impact analysis of introducing effective treatment schedule(s) in everyday clinical practice.

Being tested
Quizartinib, Treatment according to Physician's Choice, Standard of Care Chemotherapy
Keywords
AML newly diagnosed, Quizartinib added to SOC, FLT3-ITD positivity
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.

  • QuizartinibDrug

    Also called Drug Code:AC220

    20 mg coated tablets, orally administered

  • Treatment according to Physician's ChoiceDrug

    Also called PhC

    Usually daunorubicin/ cytarabine or idarubicin/Cytarabine plus FLT3 inhibitor (usually midostaurin)

  • Standard of Care ChemotherapyDrug

    Also called SOC

    Daunorubicin/ Cytarabine or Idarubicin/Cytarabine

Study groups in NCT04676243
Study groupRoleWhat they receive
Quizartinib plus standard of care (SOC)ExperimentalDaunorubicin/ Cytarabine or Idarubicin/Cytarabine and Quizartinib
Receives: Drug: Quizartinib; Drug: Standard of Care Chemotherapy
Physician's choiceActive comparatorPhysician's choice (usually Daunorubicin/ Cytarabine or Idarubicin/Cytarabine and Midostaurin)
Receives: Drug: Treatment according to Physician's Choice

What is being measured

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

  1. Modified Event-free survival (mEFS)

    mEFS is defined as the time from randomization until one of the following events, whichever occurs first: a) failure to obtain complete remission (CR) or complete remission with incomplete hematological recovery (CRi) or CR with partial recovery of peripheral blood counts (CRh) after induction therapy including one or two induction treatment cycles limited to an observational period of maximally 100 days, b) relapse from CR/CRi/CRh or c) death from any cause.

    Measured: through study completion (up to 4 years), from randomization until occurence of event a) b) or c) on individial patients' basis

Secondary outcomes (3)

  1. Overall survival (OS)

    OS is defined as the time from randomization to time of death from any cause. Patients without event are censored on the last date of follow-up.

    Measured: through study completion (up to 4 years), frome randomization until death from any cause

  2. Composite remission

    Composite remission is defined as the proportion of patients experiencing a CR/CRi/CRh after induction therapy.

    Measured: End of induction therapy, between 4 and 12 weeks

  3. Measurable residual disease (MRD)

    MRD after induction (MRDind), consolidation (MRDcons), and maintenance (MRDmaintenance) therapy, MRD is assessed by flow cytometry according to European Leukemia Net recommendations (Döhner et al, Blood 2017;129(4):424-447.)

    Measured: End of induction thearpy (28-84 days from randomization), End of consolidation therapy (140-222 days from randomization), End of maintenance therapy (140-1,120 days from randomization)

Timeline

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

  1. First posted19 Dec 2020
  2. Study startMay 2022 (estimated)
  3. Primary completionMay 2025 (estimated)
  4. Study completionDec 2025 (estimated)

Why it stopped: Study turned out no longer feasible

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 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Model description
multicenter, randomized phase in patients with FLT3-ITD positive AML comparing quizartinib in combination with SOC chemotherapy versus treatment according to physician's choice (PhC).
Masking
None (open label)
Enrolment
0 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04676243
Sponsor's protocol ID
HeLeNe 20-04
Acronym
Q-SOC
Status last verified
May 2022
First submitted
9 Dec 2020
Last updated
25 May 2022
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Quizartinib and Treatment according to Physician's Choice in people with Acute Myeloid Leukemia, run by University Hospital Heidelberg.

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 19 inclusion and 28 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: withdrawn, as of the sponsor's last update on 25 May 2022. Status can change between updates, so confirm with the study contact before making plans.

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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

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

Are results available for this study?

The study was withdrawn before enrolling participants, so there are no results.

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

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Modified Event-free survival (mEFS) (time frame: through study completion (up to 4 years), from randomization until occurence of event a) b) or c) on individial patients' basis). 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 NCT04676243.

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 25 May 2022.

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