Study of Low-Dose Intravenous Decitabine in Patients Aged > 60 Years With Acute Myeloid Leukemia

This study has been completed.
Sponsor:
Information provided by:
University Hospital Freiburg
ClinicalTrials.gov Identifier:
NCT00866073
First received: March 19, 2009
Last updated: NA
Last verified: March 2009
History: No changes posted
  Purpose

This study is an open-label phase II trial to investigate the efficacy and toxicity of low-dose decitabine (5-aza-2'-deoxycytidine) in elderly patients with acute myeloid leukemia (AML) not eligible for aggressive induction chemotherapy. AML patients above the age of 60 years (no upper age limit) who have not previously received and are not eligible for, standard induction treatment of their disease will be eligible for this trial. Decitabine will be administered as a 3 hour infusion at 15 mg/m2 three times daily on three consecutive days (total dose 135 mg/m2). In all patients with > 20000 WBC/µl, this treatment will be repeated 1 week later. In patients with white blood cells exceeding 50 000/μl, decitabine treatment will be preceded by cytoreductive doses of hydroxyurea.


Condition Intervention Phase
Acute Myeloid Leukemia
Drug: Decitabine 15 mg/m2 i.v.
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase II Study of Low-Dose Intravenous Decitabine in Patients Aged > 60 Years With Acute Myeloid Leukemia Who Are Not Eligible for Standard Induction Chemotherapy

Resource links provided by NLM:


Further study details as provided by University Hospital Freiburg:

Primary Outcome Measures:
  • response rate (complete and partial remissions, antileukemic effect) [ Time Frame: after four treatment courses of Decitabine, after 6 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • overall survival [ Time Frame: after 1 year ] [ Designated as safety issue: No ]
  • progression-free survival time [ Time Frame: after 1 year ] [ Designated as safety issue: No ]
  • toxicity of Decitabine (alone and in combination with all-trans retinoic acid) [ Time Frame: after 3-6 months ] [ Designated as safety issue: Yes ]

Enrollment: 238
Study Start Date: April 2003
Study Completion Date: March 2009
Primary Completion Date: February 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: A
Decitabine 15 mg/m2 i.v. - single arm
Drug: Decitabine 15 mg/m2 i.v.
Decitabine at 15 mg/m2 i.v. x 3 hours, three times daily on three consecutive days
Other Name: Dacogen

Detailed Description:

Hypothesis: If after 4 courses of Decitabine none out of 12 patients achieves a response (complete or partial remission, antileukemic effect), the protocol will be stopped. If at least one response is seen among the first 12 patients, 17 additional patients will be treated in an open, uncontrolled manner. If in 3 or more of these 29 patients a response is achieved, this treatment will be considered effective and will be studied further, otherwise it will be considered ineffective. At a preliminary analysis after recruitment of 29 patients, encouraging results (response rate, tolerability) are prompting continuation of recruitment, with a planned inclusion of at least 60 patients, until initiation of the planned large, controlled phase II follow-up trial. Unexpected toxicities will be carefully evaluated. 29 patients were needed for the first two steps of this phase II study, at least 60 patients are planned for the extension of the recruitment. Expected study duration for the first two steps was 15-20 months, with 35-40 months total when including the third step.

  Eligibility

Ages Eligible for Study:   60 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patients older than 60 years with acute myeloid leukemia (> 30 % bone marrow blasts) not qualifying for, or not consenting to, standard induction chemotherapy or immediate allografting
  • life expectancy > 3 months with successful treatment
  • performance status ECOG 0, 1, 2
  • age-adjusted normal cardiac, kidney, liver function (creatinine < 1.5 mg/dl unless leukemia-related, total bilirubin < 2.0 of upper normal limits)
  • patients with >50 000 leukocytes/µl in whom initial cytoreduction according to protocol is effective
  • written informed consent

Exclusion Criteria:

  • AML of FAB subtype M3
  • previous induction-type chemotherapy for MDS or AML
  • previous treatment with Decitabine, 5-azacytidine or ATRA
  • "low-dose" chemotherapy (e.g.hydroxyurea, cytosine arabinoside, melphalan) within 8 weeks prior to Decitabine treatment, except for cytoreduction of leukocytosis > 50 000/µl according to protocol - patients with > 50 000 leukocytes/µl in whom initial cytoreduction according to protocol is ineffective
  • treatment with cytokines within previous 4 weeks
  • concomitant use of any other investigational drug
  • other malignancy that is not in remission (previous chemotherapy for other malignancies is not an exclusion criteria)
  • cardiac insufficiency NYHA IV
  • HIV infection
  • other uncontrolled active infection
  • psychiatric disorder that interferes with treatment
  • known hypersensitivity to retinoids
  • contact lenses
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00866073

Locations
Germany
Medizinische Hochschule Hannover
Hannover, Niedersachsen, Germany, 30625
Klinikum der Technischen Universität Aachen
Aachen, Germany
Universitätsklinikum Düsseldorf
Düsseldorf, Germany
Katholisches Krankenhaus Hagen
Hagen, Germany
Klinikum Lüdenscheid
Luedenscheid, Germany
Universitätsklinikum Ulm
Ulm, Germany
Klinikum Villingen-Schwenningen
Villingen-Schwenningen, Germany
Netherlands
Leyenburg Hospital
The Hague, Netherlands
Sponsors and Collaborators
University Hospital Freiburg
Investigators
Principal Investigator: Michael Lübbert, Prof Dr med University Medical Center Freiburg - Dept. of Oncology/Hematoloy
  More Information

No publications provided

Responsible Party: Prof. Dr. med. M. Lübbert, Dept. of Oncology/Hematology - University Medical Center Freiburg
ClinicalTrials.gov Identifier: NCT00866073     History of Changes
Other Study ID Numbers: 00331
Study First Received: March 19, 2009
Last Updated: March 19, 2009
Health Authority: Germany: Federal Institute for Drugs and Medical Devices

Keywords provided by University Hospital Freiburg:
AML
Acute myeloid leukemia
Decitabine

Additional relevant MeSH terms:
Leukemia, Myeloid
Leukemia, Myeloid, Acute
Leukemia
Neoplasms by Histologic Type
Neoplasms
Decitabine
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses
Enzyme Inhibitors

ClinicalTrials.gov processed this record on September 30, 2014