AzTrials
AzTrials

Acute Myeloid Leukemia in RemissionPhase 2NCT04712942

Treatment of MDS/AML Patients With an Impending Hematological Relapse With AZA or ATA and Pevonedistat

A Phase 2 study testing Pevonedistat and Azacitidine in people with Acute Myeloid Leukemia in Remission and Myelodysplastic Syndromes, run by University of Leipzig at 14 sites in Germany.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

MDS/AML with MRD and impending relapse after allogeneic stem cell transplantation and/or conventional chemotherapy Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Pevonedistat and Azacitidine
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
14 participants
Where
14 sitesGermany
Study dates
1 Jan 2021to 31 Jan 2023
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

  • AML or MDS
  • continuing first CR after conventional intensive chemotherapy OR continuing CR after alloSCT
  • Confirmed MRD positivity (assessed by central lab) as defined by:
  • NPM1mut status >1% in peripheral blood or bone marrow in NPM1 mutated patients at diagnosis or
  • Patients after allogeneic transplantation, who were NPM1 unmutated at diagnosis and have a blood or marrow CD34/CD117 chimerism <80%

Who cannot join

  • Compliance with major study procedures
  • Patient does not accept bone marrow sampling during screening, primary end point visit and after the treatment.
  • Patient does not accept several blood sampling during screening, treatment (up to bi-daily) and after the treatment.
  • Safety
  • Inadequate organ function as defined in the list below:
  • White blood cell (WBC) count > 50 Gpt/L before administration of pevonedistat on Cycle 1 Day 1
Show all 49Show fewer
  • Absolute neutrophil count (ANC) < 1.5 Gpt/L
  • Platelets < 100 Gpt/L
  • Albumin < 2.7 g/dL
  • Creatinine clearance < 30 mL/min (Cockcroft und Gault formula)
  • Total bilirubin > 1.5xupper limit of normal (ULN) except in patients with Gilbert's syndrome. Patients with Gilbert's syndrome may be enrolled if direct bilirubin > 1.5x ULN of the direct bilirubin.
  • Both Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) > 3.0 ULN
  • ECOG performance status of ≥2
  • Concomitant Diseases
  • Hematological relapse
  • Liver cirrhosis or severe pre-existing hepatic impairment
  • Known severe cardiopulmonary disease (e.g. unstable angina, congestive heart failure NYHA III or IV, myocardial infarction within 6 months prior to screening, symptomatic cardiomyopathy, clinically significant arrhythmia, clinically significant pulmonary hypertension requiring pharmacologic therapy)
  • Uncontrolled high blood pressure (i.e. systolic blood pressure > 180 mm Hg, diastolic blood pressure > 95 mm Hg)
  • Confirmed prolonged rate corrected QT interval ≥ 500 msec, calculated according to institutional guidelines (Screening ECG)
  • Confirmed left ventricular ejection fraction < 50% as assessed by echocardiogram or radionuclide angiography (Screening TTE)
  • Known moderate to severe symptomatic chronic obstructive pulmonary disease, interstitial lung disease, or pulmonary fibrosis
  • Active uncontrolled infection or severe infectious disease, such as severe pneumonia, meningitis, or septicemia
  • Known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
  • Known Human Immunodeficiency Virus (HIV 1/2 antibodies)
  • Known active Hepatitis B (i.e. HBsAg reactive) or Hepatitis C (i.e., HCV RNA [qualitative] is detected). NOTE: Patients who have isolated positive hepatitis B core antibody (i.e. in the setting of negative hepatitis B surface antigen and negative hepatitis B surface antibody) must have an undetectable hepatitis B viral load. Patients who have positive hepatitis C antibody may be included if they have an undetectable hepatitis C viral load.
  • Major surgery within 14 days of randomization or a scheduled surgery during study period
  • Known central nervous system (CNS) involvement
  • Diagnosis or treatment for another malignancy within 2 years before randomization. (NOTE: Patients with non-melanoma skin cancer or carcinoma in situ of any type are not excluded if they have undergone resection. Prior diagnosis of myelodysplasia, myeloproliferative neoplasm, or aplastic anemia and treatment for that diagnosis does not lead to exclusion)
  • Any evidence of residual disease of another malignancy
  • Patients with uncontrolled coagulopathy or bleeding disorder
  • History or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject's participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator
  • Unexpected effect of HMA monotherapy
  • Prior HMA failure
  • Prior HMA treatment without subsequent allogeneic transplantation
  • Interfering Treatments
  • Any ongoing therapy with investigational agents or chemotherapeutic agents active against MDS or AML
  • BCRP inhibitors (for exceptions, see section 5.7.5) are not permitted during the study and should be stopped 14 days before first dose of the study drug
  • Exclusion criteria regarding special restrictions for females of childbearing potential
  • Current or planned pregnancy or nursing women (negative urine or serum pregnancy test within 3 days prior to receiving study treatment is needed. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test needs to be required.)
  • Female patients of childbearing potential, who are not using or not willing to use 1 highly effective method and 1 additional effective (barrier) method of contraception, at the same time, from the time of signing the informed consent through 4 months after the last dose of study drug. Note: Abstinence is acceptable if this is the usual lifestyle and preferred contraception for the subject.
  • Female patients who intend to donate eggs (ova) during the course of this study or 4 months after receiving their last dose of study drug(s).
  • Exclusion criteria regarding special restrictions for males, even if surgically sterilized (i.e. status post vasectomy)
  • Male patients, who do not agree to use an adequate method of contraception, starting with the first dose of study therapy during the entire study treatment period and through 4 months after the last dose of study drug. Note: Abstinence is acceptable if this is the usual lifestyle and preferred contraception for the subject.
  • Male patients who intend to donate sperm during the course of this study or 4 months after receiving their last dose of study drug(s).
  • Regulatory requirements
  • Age under 18 years at registration
  • Inability to provide written informed consent
  • Subject without legal capacity who is unable to understand the nature, scope, significance and consequences of this clinical trial
  • Simultaneous participation in another interventional clinical trial or participation in any clinical trial involving administration of an investigational medicinal product within 30 days prior to SHAPE trial beginning

Trial locations and contacts

14 sites in 1 country.

14 sites in 1 country

Germany14 sites

  • Medizinische Klinik IV - Hämatologie und Onkologie, Universitätsklinikum Aachen

    Aachen, 52074

  • Zentrum Hämatologie, Onkologie, Palliativmedizin, Helios Klinikum Berlin-Buch GmbH

    Berlin, 13125

  • Klinik für Innere Medizin III, Hämatologie, Onkologie, Stammzelltransplantation, Klinikum Chemnitz gGmbH

    Chemnitz, 09113

  • Hämatologie/Internistische Onkologie, Onkologische Tagesklinik

    Cottbus, 03048

  • Medizinischen Klinik und Poliklinik I / Hämatologie, Universitätsklinikum Carl Gustav Carus an der Technischen Universität Dresden

    Dresden, 01304

  • Klinik für Hämatologie, Universitätsklinikum Essen

    Essen, 45147

  • Universitätsklinik und Poliklinik für Innere Medizin IV, Onkologie, Hämatologie, Universitätsklinikum Halle (Saale)

    Halle, 06120

  • Klinik und Poliklinik für Innere Medizin II/Hämat. - Onkologie, Universitätsklinikum Jena

    Jena, 07740

  • Klinik für Innere Medizin II/ Hämatologie und Onkologie, Univ.Klinikum Schleswig-Holstein/Campus Kiel

    Kiel, 24105

  • Medizinische Klinik und Poliklinik I - Hämatologie und Zelltherapie, Hämostaseologie, Leipzig University

    Leipzig, 04103

  • Innere Medizin A/Hämatologie-Onkologie, Universitätsklinik Münster

    Münster, 48149

  • Klinik Innere Medizin III - Onko-, Häma- u. Palliativmedizin, Diakonie-Klinikum Schwäbisch Hall gGmbH

    Schwäbisch Hall, 74523

  • Klinik für Hämatologie, Onkologie & Stammzelltherapie, Helios-Klinikum Schwerin

    Schwerin, 19049

  • Abteilung für Hämatologie, Onkologie und Palliativmedizin, Robert-Bosch-Krankenhaus Stuttgart

    Stuttgart, 70376

Other trials in Germany

About this study

Official title: Treatment of MDS/AML Patients With an Impending Hematological Relapse With Azacitidine Alone or in Combination With PEvonedistat - a Randomized Phase 2 Trial

MDS/AML with MRD and impending relapse after allogeneic stem cell transplantation and/or conventional chemotherapy

Read the detailed description

Experimental arm: pevonedistat in combination with azacitidine Control arm: azacitidine alone

With the following modifications:

  • Patients on the azacitidine arm and still MRD+ at 3 months but without hematological relapse can cross over to the combination arm
  • Cross over into the combination arm is possible any time up to 9 months of study treatment if initially responding patients (at 3 months) on AZA monotherapy become MRD positive again
  • Maximum treatment duration of 1 year
  • Patients receive pevonedistat at 20 mg/m2 i.v. (d1,3,5, q4w); azacitidine is given at a standard dose of 75 mg/m² i.v. or s.c. (d1-7 or 1-5,8,9, q4w)
Being tested
Pevonedistat, Azacitidine
Medical subject headings
Myelodysplastic Syndromes, Neoplasm, Residual

What participants receive

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

  • PevonedistatDrug

    Patients receive pevonedistat at 20 mg/m2 i.v. (d1,3,5, q4w) up to 12 cycles

  • AzacitidineDrug

    azacitidine is given at a standard dose of 75 mg/m² (d1-7 or 1-5,8,9, q4w) up to 12 cycles

Study groups in NCT04712942
Study groupRoleWhat they receive
pevonedistat + azacitidineExperimentalpevonedistat in combination with azacitidine
Receives: Drug: Pevonedistat; Drug: Azacitidine
azacitidine monotherapyOtheradministration of azacitidine monotherapy
Receives: Drug: Azacitidine

What is being measured

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

  1. Measurable residual disease (MRD) status after 3 months of treatment

    To show that pevonedistat and azacitidine are more effective compared to azacitidine alone with regard to achievement of MRD negativity after 3 months of treatment.

    MRD assessment is carried out as determination of the NPM1mut status or as CD34/CD117 chimerism analysis.

    Measured: 3 months after start of treatment

Secondary outcomes (4)

  1. Overall Survival

    To describe and compare outcome measures between two strategies: pevonedistat and azacitidine in combination versus azacitidine alone with cross over option.

    Measured: From date of randomization until the date of death from any cause, assessed up to 25 months

  2. Relapse Free Survival

    To describe and compare outcome measures between two strategies: pevonedistat and azacitidine in combination versus azacitidine alone with cross over option.

    Measured: Time from randomization until hematological relapse or death from any cause (whichever comes first), assessed up to 25 Months.

  3. Impact of treatment assessed by using the validated questionnaires EORTC QLQ-C30.

    To describe and compare outcome measures between two strategies: pevonedistat and azacitidine in combination versus azacitidine alone with cross over option.

    Measured: Time from randomization until hematological relapse or death from any cause (whichever comes first)

  4. Impact of treatment assessed by using the validated questionnaires EQ-5D-5L.

    To describe and compare outcome measures between two strategies: pevonedistat and azacitidine in combination versus azacitidine alone with cross over option.

    Measured: Time from randomization until hematological relapse or death from any cause (whichever comes first), assessed up to 25 months.

Timeline

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

  1. First posted19 Jan 2021
  2. Study start1 Jan 2021
  3. Primary completion31 Jan 2023
  4. Study completion31 Jan 2023

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
Randomised
Intervention model
Parallel groups
Model description
With Cross-Over option
Masking
None (open label)
Enrolment
14 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04712942
Sponsor's protocol ID
SHAPE
Status last verified
Aug 2023
First submitted
18 Dec 2020
Last updated
21 Aug 2023
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Pevonedistat and Azacitidine in people with Acute Myeloid Leukemia in Remission and Myelodysplastic Syndromes, run by University of Leipzig at 14 sites in Germany.

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 5 inclusion and 49 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: finished, as of the sponsor's last update on 21 Aug 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 14 sites in Germany. 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?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

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?

Measurable residual disease (MRD) status after 3 months of treatment (time frame: 3 months after start of treatment). 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 NCT04712942.

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 21 Aug 2023.

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