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

NCT02446145 | Terminated Phase 2 DMC

• 2 other identifiers: TUD-DELTA1-0632014-003150-13
• Study Type: interventional
• Target: 132
• Locations: 1 country
• Sites: 15

Brief Summary

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.

Conditions

Acute Myeloid Leukemia

Outcome Measures

Primary Outcomes (1)

• treatment change-free survival

  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 Outcomes (9)

• overall survival

  up to 4 years

• relapse free survival

  up to 4 years

• overall response rate

  up to 4 years

• number of bone marrow blasts after 5, 9, and 12 months

  screening, month 5, 9 and 12

• quality of life questionnaire (QLQ-C30)

  screening, month 1, 3, 6, 9, 12

Study Arms (2)

Experimental intervention arm

EXPERIMENTAL

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

Control intervention arm

PLACEBO COMPARATOR

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

Interventions

Eltrombopag DRUG

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.

Also known as: Revolade

Experimental intervention arm

Placebo DRUG

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.

Control intervention arm

Eligibility Criteria

• Age: 65 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Older Adult (65+)

You may qualify if:

• 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
• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Technische Universität Dresden: lead
• Novartis: collaborator

Study Sites (15)

Uniklinik RWTH Aachen

Aachen, Germany

Location

Charite Campus Benjamin Franklin

Berlin, Germany

Location

Klinikum Chemnitz GmbH

Chemnitz, Germany

Location

Universitätsklinikum Dresden

Dresden, Germany

Location

Marienhospital Düsseldorf GmbH

Düsseldorf, Germany

Location

Universitätsklinikum Essen

Essen, Germany

Location

Universitätsklinikum Halle (Saale)

Halle, Germany

Location

St. Marien-Hospital Hamm

Hamm, Germany

Location

Klinikum rechts der Isar der TU München

München, Germany

Location

Klinikum Nürnberg-Nord

Nuremberg, Germany

Location

Medizinisches Versorgungszentrum für Blut- und Krebserkrankungen

Potsdam, Germany

Location

Wissenschaftskontor Nord GmbH & Co KG

Rostock, Germany

Location

Diakonie-Klinikum Schwäbisch Hall gGmbH

Schwäbisch Hall, Germany

Location

Rems-Murr-Klinikum Winnenden

Winnenden, Germany

Location

Universitätsklinikum Würzburg

Würzburg, Germany

Location

Related Links

• homepage of study group

MeSH Terms

Conditions

Leukemia, Myeloid, Acute

Interventions

eltrombopag

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Study Officials

• Uwe Platzbecker, Prof.

  Universitätsklinikum Dresden Medizinische Klinik und Poliklinik I

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 11, 2015
• First Posted: May 18, 2015
• Study Start: May 1, 2015
• Primary Completion: December 26, 2020
• Study Completion: January 25, 2023
• Last Updated: March 29, 2024

Record last verified: 2024-03

Locations

DE (15)