A Randomized Placebo-controlled Phase 2 Study of Decitabine With or Without Eltrombopag in AML Patients (DELTA)

March 27, 2024 updated by: Technische Universität Dresden

A Randomized Placebo-controlled Phase 2 Study of Decitabine With or Without Eltrombopag in AML Patients ≥65 Years of Age Not Eligible for Intensive Chemotherapy

Acute myeloid leukemia (AML) is a disease with a poor prognosis including a 5-year overall survival (OS) of app. 20% for the entire population. In particular, the outcome of elderly patients with AML is dismal and the majority of patients die within the first year after diagnosis. This is also because treatment options for elderly patients with AML significantly differ from patients of younger age. In fact, comorbid conditions are common among the elderly such as heart disease, renal insufficiency and vascular disease thus influencing the ability to withstand intensive therapy. Elderly patients are also more likely than younger patients to develop severe, life threatening infections during the course of treatment. In addition to infectious complications, hemorrhages due to severe thrombocytopenia are responsible for morbidity and mortality in a considerable amount of patients. Compared with younger AML patients, elderly individuals with AML display a higher incidence of poor-prognosis karyotypes, of a preceding myelodysplastic syndrome (MDS), and greater expression of proteins involved in intrinsic resistance to chemotherapeutic agents. As a result conventional anthracycline based chemotherapy is only infrequently used in patients above the age of 65 years. Based on a recent randomized trial (Kantarjian et al. 2012) low-intensity epigenetic therapy with decitabine (DAC) has become the first-line standard of care in most European countries including Germany. Nevertheless, even with this treatment the 1-year OS is approximately 30 % only. Furthermore, severe thrombocytopenia is a main side effect of this therapy and can prevent adequate continuation of treatment being crucially for treatment success. Supportive care with platelet transfusions is effective primarily only over short periods and often requires hospitalization and therefore lowers the quality of life of these patients in their palliative situation. Therefore, patients could benefit from an approach aiming at an increase of platelet counts through combined use of Azacitidine (AZA) or DAC with an oral thrombopoietin receptor agonist like eltrombopag (EPAG). This could allow for a better adherence to DAC/AZA therapy by preventing dose delays due to prolonged thrombocytopenia. Additionally, the potential antileukemic effect of EPAG could also be beneficial for these AML patients.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Terminated

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

The DELTA-trial is designed as a two-arm, double-blind, multicenter randomized-controlled phase- II study of EPAG or placebo in combination with standard-dose DAC/AZA treatment as concomitant medication in subjects at least 65 years of age with AML not eligible for intensive chemotherapy and planned therapy with Decitabine (DAC)/Azacitidine(AZA). Patients will be randomized 1:1 into the experimental study arm and the control study arm. EPAG 200 mg (100 mg for East Asian patients) once daily has been selected as the starting dose for this study because this regimen has been investigated to be safe and potentially effective in increasing platelet counts in patients with AML. Concomitant medication with DAC/AZA will be according to the european label and the summary of product characteristics. There will be a dose adjustment of EPAG depending on the platelet counts obtained on day 1 of a planned DAC/AZA cycle. EPAG or placebo will be taken for 14 days in each treatment cycle starting on day 12 with a minimum treatment gab of 2 days before and after each DAC/AZA course.

Concomitant medication will be either Decitabine (DAC) 20 mg/m2 body surface i.v. over 30 minutes on days 1-5 of each cycle or Azacitidine (AZA) 75 mg/m2 body surface sc. on days 1-7. One cycle lasts 28 days.

Patients will receive medication as long as they benefit from treatment and in the absence of relevant adverse events indicating a treatment discontinuation; but for a maximum of 12 cycles. During Follow Up (up to 4 years) patient survival and first treatment change will be observed.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
132

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.
  • Name: Julia Kalinka
  • Phone Number: 0351 458 3089

Study Locations

  • Germany
      • Aachen, Germany
        • Uniklinik RWTH Aachen
      • Berlin, Germany
        • Charite Campus Benjamin Franklin
      • Chemnitz, Germany
        • Klinikum Chemnitz GmbH
      • Dresden, Germany
        • Universitätsklinikum Dresden
      • Düsseldorf, Germany
        • Marienhospital Düsseldorf GmbH
      • Essen, Germany
        • Universitatsklinikum Essen
      • Halle, Germany
        • Universitatsklinikum Halle (Saale)
      • Hamm, Germany
        • St. Marien-Hospital Hamm
      • München, Germany
        • Klinikum rechts der Isar der TU München
      • Nürnberg, Germany
        • Klinikum Nürnberg-Nord
      • Potsdam, Germany
        • Medizinisches Versorgungszentrum für Blut- und Krebserkrankungen
      • Rostock, Germany
        • Wissenschaftskontor Nord GmbH & Co KG
      • Schwäbisch Hall, Germany
        • Diakonie-Klinikum Schwäbisch Hall gGmbH
      • Winnenden, Germany
        • Rems-Murr-Klinikum Winnenden
      • Würzburg, Germany
        • Universitatsklinikum Wurzburg

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

65 years and older (Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Newly diagnosed AML (including therapy-related or with antecedent MDS) other than acute promyelocytic leukemia (APL) according to WHO criteria, i.e. bone marrow aspirate / biopsy or peripheral blood must contain ≥20% blasts in AML defined by cytogenetic aberrations according to WHO the proportion of blasts may be <20%
  • Age ≥ 65 years
  • Eastern Cooperative Oncology Group performance status (ECOG) 0-3
  • patients not eligible for intensive induction therapy (according to investigator's decision)
  • planned therapy with DAC/AZA
  • platelet count <75 Gpt/L taken within 4 weeks prior to randomization

  • adequate liver function as assessed by the following laboratory requirements during screening (within 4 weeks prior to study inclusion):

    • Total bilirubin ≤ 3 times the upper limit of normal (except for Gilbert's Syndrome)
    • Alanine transaminase (ALAT) and Aspartate transaminase (ASAT) ≤ 3 times upper limit of normal
  • signed Informed Consent

Exclusion Criteria:

  • acute promyelocytic leukemia (APL)
  • history of higher-risk MDS or AML treatment with thrombopoietin receptor (TPO-R) agonists, hypomethylating agents or intensive chemotherapy
  • substance abuse, medical, psychological or social conditions that may interfere with the patient's participation in the study or evaluation of the study results
  • treatment with an investigational drug within 30 days or 5 half-lives (whichever is longer) preceding to first dose of study mediation
  • uncontrolled active infection
  • New York Heart Association (NYHA) stage ≥ 2 due to heart insufficiency
  • positive Human Immunodeficiency Virus (HIV) or Hepatitis B / C serology
  • patients unable to swallow medication
  • known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to EPAG or DAC or excipients that contraindicates their participation

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Experimental intervention arm

Eltrombopag daily from day 12 to 25: 200 mg/day p.o. (100 mg for east asian patients) dose modification 100 mg up to 300 mg/d p.o. (50 - 150 mg for east asian patients)

  • concomitant medication: either Decitabine days 1-5 of each cycle: 20 mg/sqm i.v. over 30 minutes or Azacitidine (AZA) days 1-7 of each cycle: 75 mg/sqm s.c.
  • one cycle lasts 28 days
Drug: Eltrombopag

Patients will receive EPAG in addition to their background standard treatment with Decitabine/Azacitidine

- concomitant medication: either Decitabine days 1-5 of each cycle: 20 mg/sqm i.v. over 30 minutes or Azacitidine (AZA) days 1-7 of each cycle: 75 mg/sqm s.c.

Other Names:
  • Revolade
Placebo Comparator: Control intervention arm

Placebo daily from day 1: 200 mg/day p.o. (100 mg for east asian patients) dose modification 100 mg up to 300 mg/d p.o. (50 - 150 mg for east asian patients)

  • concomitant medication: either Decitabine days 1-5 of each cycle: 20 mg/sqm i.v. over 30 minutes or Azacitidine (AZA) days 1-7 of each cycle: 75 mg/sqm s.c.
  • one cycle lasts 28 days
Drug: Placebo

Patients will receive Placebo in addition to their background standard treatment with Decitabine/Azacitidine

- concomitant medication: either Decitabine days 1-5 of each cycle: 20 mg/sqm i.v. over 30 minutes or Azacitidine (AZA) days 1-7 of each cycle: 75 mg/sqm s.c.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
treatment change-free survival
Time Frame: up to 4 years
time from randomization until day one of the new disease modifying treatment or death as the primary endpoint of this study
up to 4 years

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
incidence of serious adverse events (SAE)
Time Frame: up to 4 years
incidence of SAE including death, incidence of bleeding events and hospitalization rate and duration
up to 4 years
overall survival
Time Frame: up to 4 years
Overall survival is defined as months from day 1 of cycle 1 until death and is calculated as (date of death - date of day 1 of cycle 1 + 1) / 30.43
up to 4 years
relapse free survival
Time Frame: up to 4 years
Relapse free survival is defined for patients who achieved CR, CRi, CRc, or CRm.
up to 4 years
overall response rate
Time Frame: up to 4 years
Overall response is defined as achievement of stable disease (SD), partial remission (PR), or complete remission (CR, including CRi, CRc, CRm) at any time during treatment period.
up to 4 years
number of bone marrow blasts after 5, 9, and 12 months
Time Frame: screening, month 5, 9 and 12
Bone marrow blasts are determined locally and by central review. The blast count from the central review is preferred in the analysis. In case of missing blast count from central review the locally determined blast count will be used for analysis.
screening, month 5, 9 and 12
quality of life questionnaire (QLQ-C30)
Time Frame: screening, month 1, 3, 6, 9, 12
Quality of life is assessed by the EORTC QLQ-C30 and the SF36 questionnaires. Quality of life will be assessed only in patients with complete baseline assessment. QOL will only be assessed in analysis sets for which information is available for more than 75% of individuals.
screening, month 1, 3, 6, 9, 12
Short Form questionnaire 36 (SF-36)
Time Frame: screening, month 1, 3, 6, 9, 12
Quality of life is assessed by the EORTC QLQ-C30 and the SF36 questionnaires. Quality of life will be assessed only in patients with complete baseline assessment. QOL will only be assessed in analysis sets for which information is available for more than 75% of individuals.
screening, month 1, 3, 6, 9, 12
median platelet counts
Time Frame: month 1 - 12
Platelet counts are analysed as recorded in the study database.
month 1 - 12
number of platelet transfusions
Time Frame: month 1 - 4
Number of platelet transfusions during cycle 1-4 is defined as the cumulative sum of platelet transfusions documented in cycles 1 to 4.
month 1 - 4

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Technische Universität Dresden

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Novartis

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Uwe Platzbecker, Prof., Universitätsklinikum Dresden Medizinische Klinik und Poliklinik I

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
May 1, 2015

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
December 26, 2020

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
January 25, 2023

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
February 11, 2015

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
May 13, 2015

First Posted (Estimated)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
May 18, 2015

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
March 29, 2024

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
March 27, 2024

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
March 1, 2024

More Information

Terms related to this study

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • TUD-DELTA1-063
  • 2014-003150-13 (EudraCT Number)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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