DaunoXome + Ara-C vs Daunorubicin + Ara-C in Elderly AML
Information source: Gruppo Italiano Malattie EMatologiche dell'Adulto
Information obtained from ClinicalTrials.gov on June 20, 2008
Link to the current ClinicalTrials.gov record.
Condition(s) targeted: AML; Elderly
Intervention: DaunoXome (Drug); Daunorubicine (Drug)
Phase: Phase 3
Sponsored by: Gruppo Italiano Malattie EMatologiche dell'Adulto
Official(s) and/or principal investigator(s):
Franco MANDELLI, Prof, Principal Investigator, Affiliation: Università di Roma "La Sapienza"
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.
Official title: DaunoXome (Liposomal Daunorubicin) Plus Ara-C Versus Daunorubicin Plus Ara-C in Elderly AML Patients.A Randomized Phase III Study.
Study design: Treatment, Randomized, Open Label, Active Control, Parallel Assignment, Safety/Efficacy Study
Primary outcome: Efficacy and safety of DaunoXome in association with cytosine arabinoside in terms of reduction of induction deaths respect to standard "3+7" chemotherapy
Secondary outcome: Efficacy, in terms of DFS, of maintenance therapy with low-dose of Ara-C plus ATRA versus no maintenance therapy
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.
Minimum age: 61 Years.
Maximum age: 75 Years.
- Previously untreated AML (including AML after MDS) with > 20% marrow blasts (new WHO
- 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
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
- 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.
Locations and Contacts
GIMEMA's Web page
Zittoun RA, Mandelli F, Willemze R, de Witte T, Labar B, Resegotti L, Leoni F, Damasio E, Visani G, Papa G, et al. Autologous or allogeneic bone marrow transplantation compared with intensive chemotherapy in acute myelogenous leukemia. European Organization for Research and Treatment of Cancer (EORTC) and the Gruppo Italiano Malattie Ematologiche Maligne dell'Adulto (GIMEMA) Leukemia Cooperative Groups. N Engl J Med. 1995 Jan 26;332(4):217-23.
Starting date: October 2001
Ending date: November 2005
Last updated: January 8, 2008