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

NCT ID: NCT00866073

Last Updated: 2009-03-20

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 238 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2003-04-30
• Study Completion Date: 2009-03-31

Brief Summary

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.

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.

Conditions

Acute Myeloid Leukemia

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

A

Decitabine 15 mg/m2 i.v. - single arm

Group Type: EXPERIMENTAL

Decitabine 15 mg/m2 i.v.

Intervention Type: DRUG

Decitabine at 15 mg/m2 i.v. x 3 hours, three times daily on three consecutive days

Interventions

Decitabine 15 mg/m2 i.v.

Decitabine at 15 mg/m2 i.v. x 3 hours, three times daily on three consecutive days

Intervention Type: DRUG

Other Intervention Names

Dacogen

Eligibility 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
• cardiac insufficiency NYHA IV
• HIV infection
• other uncontrolled active infection
• psychiatric disorder that interferes with treatment
• known hypersensitivity to retinoids
• contact lenses

• Minimum Eligible Age: 60 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University Hospital Freiburg

OTHER

Sponsor Role: lead

Responsible Party

Dept. of Oncology/Hematology - University Medical Center Freiburg

Principal Investigators

Michael Lübbert, Prof Dr med

Role: PRINCIPAL_INVESTIGATOR

University Medical Center Freiburg - Dept. of Oncology/Hematoloy

Locations

Medizinische Hochschule Hannover

Hanover, Lower Saxony, Germany

Klinikum der Technischen Universität Aachen

Aachen, , Germany

Universitätsklinikum Düsseldorf

Düsseldorf, , Germany

Katholisches Krankenhaus Hagen

Hagen, , Germany

Klinikum Lüdenscheid

Lüdenscheid, , Germany

Universitätsklinikum Ulm

Ulm, , Germany

Klinikum Villingen-Schwenningen

Villingen-Schwenningen, , Germany

Leyenburg Hospital

The Hague, , Netherlands

Countries

Germany; Netherlands

Other Identifiers

00331

Identifier Type: -

Identifier Source: org_study_id