Trial document





This study has been imported from ClinicalTrials.gov without additional data checks.
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  DRKS00003937

Trial Description

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Title

A Randomised Phase III Study to Compare Arsenic Trioxide (ATO) Combined to ATRA Versus Standard ATRA and Anthracycline-Based Chemotherapy (AIDA Regimen) for Newly Diagnosed, Non High-Risk Acute Promyelocytic Leukemia

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Trial Acronym

APL0406

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URL of the Trial

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Brief Summary in Lay Language

Open label, randomised, phase III multicenter trial.

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Brief Summary in Scientific Language

- Arm I:

- Induction therapy: Patients receive oral tretinoin twice daily and arsenic
trioxide IV over 2 hours on days 1-60. Patients achieving hematological complete
remission go on to receive consolidation therapy.

- Consolidation therapy: Patients receive oral tretinoin twice daily on days 1-14.
Treatment with tretinoin repeats every 4 weeks for up to 7 courses. Patients also
receive arsenic trioxide IV over 2 hours on days 1-5 in weeks 1-4. Treatment with
arsenic trioxide repeats every 8 weeks for up to 4 courses.

- Arm II:

- Induction therapy: Patients receive tretinoin as in arm I induction therapy and
idarubicin IV over 20 minutes on days 2, 4, 6, and 8. Patients achieving
hematological complete remission go on to receive consolidation therapy.

- Consolidation therapy: Patients receive oral tretinoin twice daily on days 1-45,
idarubicin IV over 20 minutes on days 1-4 and day 31, and mitoxantrone
hydrochloride IV over 30 minutes on days 16-20.

Marrow samples are collected after completion of consolidation therapy and analyzed by
reverse transcriptase-PCR for molecular remission. Patients achieving molecular remission
(PML-RARa negative) go on to receive maintenance therapy.

- Maintenance therapy: Patients receive oral mercaptopurine once daily and methotrexate
intramuscularly once weekly for 3 months. Treatment with mercaptopurine and
methotrexate repeats every 3 months for 7 courses. After completion of course 1 of
mercaptopurine and methotrexate, patients receive oral tretinoin once daily on days
1-15*. Treatment with tretinoin repeats every 3 months for 6 courses.

NOTE: *Patients do not receive mercaptopurine and methotrexate during tretinoin
administration.

After completion of study therapy, patients are followed periodically for 5 years.

As of 14th September 2010, all patients needed to evaluate the primary endpoint (162
patients) have been recruited but the trial accrual continued in order to assess one
secondary outcome (QoL)."

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Organizational Data

  •   DRKS00003937
  •   2012/05/04
  •   2007/06/04
  •   yes
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Secondary IDs

  •   2006-006188-22 
  •   NCT00482833  (ClinicalTrials.gov)
  •   APL0406  (Gruppo Italiano Malattie EMatologiche dell'Adulto)
  •   GIMEMA-SAL-APL0406 
  •   EUDRACT-2006-006188-22 
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Health Condition or Problem studied

  •   Leukemia
  •   C92.4 -  Acute promyelocytic leukaemia
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Interventions/Observational Groups

  •   Drug: arsenic trioxide
  •   Drug: idarubicin
  •   Drug: mercaptopurine
  •   Drug: methotrexate
  •   Drug: all-trans retinoic acid
  •   Drug: all-trans retinoic acid (ATRA)
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Characteristics

  •   Interventional
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  •   Randomized controlled trial
  •   Open (masking not used)
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  •   Active control (effective treament of control group)
  •   Treatment
  •   Parallel
  •   III
  •   [---]*
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Primary Outcome

- Event-free survival; time frame: At maximum 3.5 years from study entry; As of 14th september 2010, all patients needed to evaluate the primary endpoint have been recruited.

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Secondary Outcome

- Rate of hematological complete remission; time frame: At maximum 60 days from induction therapy start
- Overall survival rate; time frame: At 2 years from study entry
- Rate of cumulative incidence of relapse; time frame: At 2 years from study entry
- Incidence of hematological and non-hematological toxicity episodes during treatment as assessed by CTC-NCI; time frame: At maximum 60 days from induction therapy start and at maximum 225 days from consolidation therapy start
- Rate of molecular remission after 3rd consolidation course; time frame: At maximum 225 days grom consolidation therapy start
- Assessment of acute promyelocytic leukemia/RARa transcript level reduction after induction and during consolidation therapy; time frame: At maximum 60 days from induction therapy start and at maximum 225 days from consolidation therapy start
- Quality of life at the end of induction therapy and at the end of the 3rd consolidation course; time frame: At maximum 60 days from induction therapy start and at maximum 225 days from consolidation therapy start
- Event free survival; time frame: At 2 years from study entry
- Total hospitalization days during study therapy; time frame: At maximum 3.5 years from study entry
- Event-free survival rate in the two arms; time frame: At 2 years from study entry

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Countries of Recruitment

  •   Austria
  •   Germany
  •   Italy
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Locations of Recruitment

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Recruitment

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  •   2007/08/31
  •   276
  •   Multicenter trial
  •   International
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Inclusion Criteria

  •   Both, male and female
  •   18   Years
  •   70   Years
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Additional Inclusion Criteria

Inclusion criteria

- Signed written informed consent according to IGH/EU/GCP and national local laws

- Newly diagnosed APL by cytomorphology, confirmed also by molecular analysis*.

- Age ≤18 < 71 years

- WHO performance status 0 -2 included

- WBC at diagnosis ≤ 10 x 109/L

- Serum total bilirubin ≤ 3.0 mg/dL (≤ 51µmol/L)

- Serum creatinine ≤ 3.0 mg/dL (≤ 260 µmol/L)

The confirmation of diagnosis at genetic level (microspeckled PML nuclear distribution by
PGM3 monoclonal antibody and/or PML/RARa fusion by RT-PCR and/or demonstration of
t(15;17) by karyotyping) will be mandatory for patient eligibility. However, in order to
avoid delay in treatment initiation, patients can be randomised on the basis of
morphologic diagnosis only and before the results of genetic tests are available.

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Exclusion Criteria

Exclusion criteria

- Age < 18 and ≥ 71

- WBC at diagnosis > 10 x 109/L

- Other active malignancy at time of study entry

- Lack of diagnostic confirmation at genetic level

- Significant arrhythmias, EKG abnormalities (*see below) or neuropathy

- Other cardiac contraindications for intensive chemotherapy (L-VEF <50%)

- Uncontrolled, life-threatening infections

- Severe non-controlled pulmonary or cardiac disease

- Women who are either pregnant or breast feeding, or of child-bearing potential,
defined as all women physiologically capable of becoming pregnant, UNLESS they meet
one of the following definitions:

- Amenorrhea;

- post surgical bilateral oophorectomy with or without hysterectomy;

- using a highly effective method of birth control (defined as those which result
in a failure rate less than 1% per year) when used consistently and correctly
such as implants, injectables, oral contraceptives, IUDs, sexual abstinence or
vasectomized partner.

- Concomitant severe psychiatric disorder

- HIV positivity

*EKG abnormalities:

- Congenital long QT syndrome;

- History or presence of significant ventricular or atrial tachyarrhythmia

- Clinically significant resting bradycardia (<50 beats per minute)

- QTc > 450 msec on screening EKG (using the QTcF formula detailed on page 18)

- Right bundle branch block plus left anterior hemiblock, bifascicular block

- Use of other investigational drugs at the time of enrolment or within 30 days before
study entry

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Addresses

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    • Gruppo Italiano Malattie EMatologiche dell'Adulto
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    •   [---]*
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    • Azienda Ospedaliera Universitaria Policlinico Tor Vergata
    • Francesco Lo Coco, MD 
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    • Azienda Ospedaliera Universitaria Policlinico Tor Vergata
    • Francesco Lo Coco, MD 
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Sources of Monetary or Material Support

  • start of 1:1-Block address materialSupport
    • Bitte wenden Sie sich an den Sponsor / Please refer to primary sponsor
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Status

  •   Recruiting complete, follow-up continuing
  •   [---]*
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Trial Publications, Results and other Documents

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The parameters in ClinicalTrials.gov and DRKS are not identical. Therefore the data import from ClinicalTrials.gov required adjustments. For full details please see the DRKS FAQs .
  •   91
  •   2013/10/30
* This entry means the parameter is not applicable or has not been set.