AMLPhase 3NCT00589082
DaunoXome + Ara-C vs Daunorubicin + Ara-C in Elderly AML
A Phase 3 study testing DaunoXome and Daunorubicine in people with AML and Elderly, run by Gruppo Italiano Malattie EMatologiche dell'Adulto.
Trial summary
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… Read more about this study
- Who is it for?
- Ages 61 to 75 years
- What is being tested?
- DaunoXome and Daunorubicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- Not given
- Where
- No sites listed yet
- Study dates
- Oct 2001to Nov 2005
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 61 to 75 years
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 19Show fewer
- 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.
About this study
Official title: DaunoXome (Liposomal Daunorubicin) Plus Ara-C Versus Daunorubicin Plus Ara-C in Elderly AML Patients.A Randomized Phase III Study.
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.
Read the 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.
- Being tested
- DaunoXome, Daunorubicine
- Keywords
- AML, elderly, DaunoXome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DaunoXomeDrug
DaunorubicineDrug
| Study group | Role | What they receive |
|---|---|---|
| 1 | Active comparator | standard 3+7 Receives: Drug: Daunorubicine |
| 2 | Experimental | DNX 3+7 Receives: Drug: DaunoXome |
What is being measured
The primary outcome is the main question the study is designed to answer.
Efficacy and safety of DaunoXome in association with cytosine arabinoside in terms of reduction of induction deaths respect to standard "3+7" chemotherapy
Secondary outcomes (1)
Efficacy, in terms of DFS, of maintenance therapy with low-dose of Ara-C plus ATRA versus no maintenance therapy
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Jan 2008 (estimated)
- Study startOct 2001
- Primary completionNov 2005
- Study completionNov 2005
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for AMLStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
Sponsor and investigators
- Lead sponsor
- Gruppo Italiano Malattie EMatologiche dell'Adulto
- Sponsor type
- University, hospital or other
- Investigators
- Franco MANDELLI, Prof, Principal investigator, Università di Roma "La Sapienza"
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00589082
- Sponsor's protocol ID
- GSI 103-AMLE
- Status last verified
- Dec 2007
- First submitted
- 24 Dec 2007
- Last updated
- 9 Jan 2008
- Results posted
- No
- Data monitoring committee
- No
Publications
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. doi: 10.1056/NEJM199501263320403.
PubMed 7808487
Study at a glance
From the registry record, last updated by the sponsor on 9 Jan 2008. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- DaunoXome (Liposomal Daunorubicin) Plus Ara-C Versus Daunorubicin Plus Ara-C in Elderly AML Patients.A Randomized Phase III Study.
- ClinicalTrials.gov ID
- NCT00589082
- Acronym / sponsor ID
- GSI 103-AMLE
- Keywords
- AML, elderly, DaunoXome
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Lead sponsor
- Gruppo Italiano Malattie EMatologiche dell'AdultoUniversity, hospital or other
- Study start
- Oct 2001
- Primary completion
- Nov 2005 (actual)
- Study completion
- Nov 2005 (actual)
- First posted
- 9 Jan 2008 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 1 | Active comparator | Drug: Daunorubicinestandard 3+7 |
| 2 | Experimental | Drug: DaunoXomeDNX 3+7 |
Who may qualify
- Ages
- 61 to 75 years
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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
Key exclusion criteria (19 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| DaunoXome | Drug | 2 |
| Daunorubicine | Drug | 1 |
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
1 secondary outcome
Efficacy, in terms of DFS, of maintenance therapy with low-dose of Ara-C plus ATRA versus no maintenance therapy
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Jan 2008.
- Background: PubMed 7808487Zittoun 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. doi: 10.1056/NEJM199501263320403.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Franco MANDELLI, Prof principal investigator
Università di Roma "La Sapienza"
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing DaunoXome and Daunorubicine in people with AML and Elderly, run by Gruppo Italiano Malattie EMatologiche dell'Adulto.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 19 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 9 Jan 2008. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Efficacy and safety of DaunoXome in association with cytosine arabinoside in terms of reduction of induction deaths respect to standard "3+7" chemotherapy. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00589082, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Jan 2008.