DaunoXome + Ara-C vs Daunorubicin + Ara-C in Elderly AML

This study has been completed.
Sponsor:
Information provided by:
Gruppo Italiano Malattie EMatologiche dell'Adulto
ClinicalTrials.gov Identifier:
NCT00589082
First received: December 24, 2007
Last updated: January 8, 2008
Last verified: December 2007
  Purpose

Overall results in the treatment of middle aged adults acute myelogenous leukemia (AML) are substantially improved in the last decade, with complete remission (CR) rates established to values of 70 to 80per cent and also encouraging long-term outcome, especially in patients who can tolerate intensified post remissional treatment strategies. On the contrary, there has been little progress in the treatment of older patients. In these patients the response rate generally range between 40 and 60per cent, and overall survival at 2 years is often less than 10 per cent.

Usually, a combination of anthracyclines daunomycin DNR or doxorubicin and cytarabyne Ara-C has been utilized for the remission-induction treatment, with schedules similar to those utilized in younger cases, for patients eligible to intensive treatments. Variation of the dose of DNR has not brought any significant benefit. The EORTC HOVON randomized trial AML9 compared two drugs in induction for previously untreated patients. DNR versus Mithoxantrone (MTZ). MTZ induction therapy produces a slightly better CR rate than DNR-containing regimen (47per cent vs 38per cent, P equals 0.069), without any significant effect on remission duration and survival. The DFS probability between the two treatment arms was not different. The median DFS estimates were 39 weeks in both groups. The DFS rate at 5 years was 8per cent. Also the duration of survival was similar (p equals 0.23) in the two treatment groups. Median survival estimates were 36 weeks (DNR) and 39 weeks (MTZ). The percentage of patients still alive at 5 years were 6per cent and 9per cent respectively.


Condition Intervention Phase
AML
Elderly
Drug: DaunoXome
Drug: Daunorubicine
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: DaunoXome (Liposomal Daunorubicin) Plus Ara-C Versus Daunorubicin Plus Ara-C in Elderly AML Patients.A Randomized Phase III Study.

Resource links provided by NLM:


Further study details as provided by Gruppo Italiano Malattie EMatologiche dell'Adulto:

Primary Outcome Measures:
  • Efficacy and safety of DaunoXome in association with cytosine arabinoside in terms of reduction of induction deaths respect to standard "3+7" chemotherapy [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Efficacy, in terms of DFS, of maintenance therapy with low-dose of Ara-C plus ATRA versus no maintenance therapy [ Designated as safety issue: No ]

Study Start Date: October 2001
Study Completion Date: November 2005
Primary Completion Date: November 2005 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: 1
standard 3+7
Drug: Daunorubicine
Experimental: 2
DNX 3+7
Drug: DaunoXome

Detailed Description:

It can be stated that single agent DaunoXome seems associated with a level of anti-leukemic activity at least equivalent to the conventional drugs available. In addition, the safety profile of DaunoXome either as a single agent either as a combination with Ara-C seems improved with respect to the conventionally administered anthracyclines. Therefore, it seems warranted to further explore the anti-leukemic activity, the toxicity and the long term results of DaunoXome as a treatment for AML in association with Ara-C against the parent compound daunorubicin. In particular, we propose a study to evaluate standard 3+7 schedule versus the same schedule with DaunoXome instead of daunorubicine as front line treatment in AML patients older than 60 years. Patients achieving a CR will receive a consolidation cycle with the same drugs at the same doses. After consolidation, patients in CR will be randomized to receive a maintenance treatment with low-dose Ara-C plus Atra versus no treatment.

  Eligibility

Ages Eligible for Study:   61 Years to 75 Years
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Previously untreated AML (including AML after MDS) with > 20% marrow blasts (new WHO classification)
  • Age ≥ 61 <75 years
  • AML evoluted after MDS are eligible if not previously treated with antiblastic drugs.
  • Performance status ≥ 70 (Karnofsky) or ≤ 2 (WHO)
  • Signed informed consent from the patient

Exclusion Criteria:

Version 3.0 - february 2001 - CONFIDENTIAL 9

  • Patients already treated for their AML with other cytotoxic drugs (except no more than 7 days of Corticosteroids)
  • Acute promyelocitic leukemia (FAB M3 or M3v)
  • Blast crisis of chronic myeloid leukemia or leukemia supervening after other
  • myeloproliferative disease
  • Concomitant progressive malignant disease
  • Presence of meningeal disease
  • History of recent myocardial infarction (within previous 12 months), significant congestive heart failure, life threatening arrhythmia, or cardiovascular disease of Class II or greater according to the New York Heart Association Functional Classification (NYHAFC).
  • Abnormal cardiac ejection fraction (45% or less).
  • Abnormal hepatic function (ALAT/ASAT or bilirubin >3 N ).
  • Abnormal renal function (creatinine >3 N)
  • Active bacterial, fungal or viral infection as documented by positive cultures, radiological imaging, clinical signs, septic fever or septic shock symptoms.
  • Patients who recover from the infection could be eligible.
  • History of hypersensitivity to one of the liposomal constituents.
  • Severe pulmonary, neurological or psychiatric disease.
  • People unable to give informed consent.
  • Presence of any phychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow up schedule.
  • HIV positivity
  • Intercurrent organ damage or medical problems that would interfere with therapy.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00589082

Sponsors and Collaborators
Gruppo Italiano Malattie EMatologiche dell'Adulto
Investigators
Principal Investigator: Franco MANDELLI, Prof Università di Roma "La Sapienza"
  More Information

Additional Information:
Publications:
Responsible Party: Prof. Franco Mandelli, GIMEMA
ClinicalTrials.gov Identifier: NCT00589082     History of Changes
Other Study ID Numbers: GSI 103-AMLE
Study First Received: December 24, 2007
Last Updated: January 8, 2008
Health Authority: Italy: The Italian Medicines Agency

Keywords provided by Gruppo Italiano Malattie EMatologiche dell'Adulto:
AML
elderly
DaunoXome

Additional relevant MeSH terms:
Cytarabine
Daunorubicin
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses
Antiviral Agents
Anti-Infective Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antibiotics, Antineoplastic

ClinicalTrials.gov processed this record on April 17, 2014