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History of Changes for Study: NCT00482833
Arsenic Trioxide and Tretinoin Compared With Tretinoin, Idarubicin, Mitoxantrone, Methotrexate, and Mercaptopurine In Treating Patients With Newly Diagnosed Acute Promyelocytic Leukemia
Latest version (submitted October 10, 2022) on ClinicalTrials.gov
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Study Record Versions
Version A B Submitted Date Changes
1 June 4, 2007 None (earliest Version on record)
2 June 6, 2007 Study Description, Eligibility, Outcome Measures, Conditions, Study Status and Study Identification
3 June 13, 2007 Study Status
4 August 6, 2007 Contacts/Locations and Study Status
5 September 25, 2007 Study Description and Study Status
6 October 25, 2007 Study Status
7 December 25, 2007 Study Status
8 May 23, 2008 Arms and Interventions and Study Status
9 July 23, 2008 Study Design and Study Status
10 November 29, 2011 Study Identification, Outcome Measures, Study Status, Arms and Interventions, Contacts/Locations, Study Design, Study Description, Sponsor/Collaborators, References, Eligibility and Oversight
11 December 16, 2011 Contacts/Locations and Study Status
12 August 20, 2012 Contacts/Locations, Study Status, Outcome Measures and Study Identification
13 November 12, 2012 Study Status and Study Description
14 December 28, 2012 Study Status, Outcome Measures, Study Description and Study Identification
15 January 9, 2013 Recruitment Status, Study Status, Contacts/Locations and Study Design
16 January 10, 2013 Study Description and Study Status
17 January 30, 2014 Study Status
18 January 27, 2015 Study Status
19 July 31, 2015 Study Status
20 September 14, 2016 Study Status
21 February 16, 2017 Study Status
22 January 23, 2018 Study Status
23 March 21, 2018 Contacts/Locations and Study Status
24 October 19, 2018 Study Status
25 December 31, 2021 Study Status
26 October 10, 2022 Recruitment Status and Study Status
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Study NCT00482833
Submitted Date:  June 4, 2007 (v1)
Open or close this module Study Identification
Unique Protocol ID: CDR0000547686
Brief Title: Arsenic Trioxide and Tretinoin Compared With Tretinoin, Idarubicin, Mitoxantrone, Methotrexate, and Mercaptopurine In Treating Patients With Newly Diagnosed Acute Promyelocytic Leukemia
Official 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
Secondary IDs: GIMEMA-DSL-APL0406
EUDRACT-2006-006188-22
EU-20725
Open or close this module Study Status
Record Verification: May 2007
Overall Status: Recruiting
Study Start: March 2007
Primary Completion:
Study Completion:
First Submitted: June 4, 2007
First Submitted that
Met QC Criteria:		 June 4, 2007
First Posted: June 5, 2007 [Estimate]
Last Update Submitted that
Met QC Criteria:		 June 4, 2007
Last Update Posted: June 5, 2007 [Estimate]
Open or close this module Sponsor/Collaborators
Sponsor: Gruppo Italiano Malattie EMatologiche dell'Adulto
Responsible Party:
Collaborators:
Open or close this module Oversight
U.S. FDA-regulated Drug:
U.S. FDA-regulated Device:
Data Monitoring:
Open or close this module Study Description
Brief Summary:

RATIONALE: Drugs used in chemotherapy work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) may kill more cancer cells. It is not yet known which combination chemotherapy regimen is more effective in treating acute promyelocytic leukemia.

PURPOSE: This randomized phase III trial is studying giving arsenic trioxide together with tretinoin to see how well it works compared with giving tretinoin together with idarubicin, mitoxantrone, methotrexate, and mercaptopurine in treating patients with newly diagnosed acute promyelocytic leukemia.
Detailed Description:

OBJECTIVES:

Primary

  • Compare the event-free survival of patients with newly diagnosed acute promyelocytic leukemia receiving arsenic trioxide and tretinoin vs combination chemotherapy comprising tretinoin, idarubicin, mitoxantrone hydrochloride, methotrexate, and mercaptopurine.

Secondary

  • Compare the complete response rate in patients receiving these regimens.
  • Compare the overall survival rate of patients receiving these regimens.
  • Compare the complete and incomplete response rate in patients receiving these regimens.
  • Compare the toxicity profile of these regimens in these patients.
  • Compare the kinetics of minimal residual disease in patients receiving these regimens.
  • Compare the duration of hospitalization of patients receiving these regimens.
  • Compare the quality of life in these patients receiving these regimens.

OUTLINE: This is a multicenter, randomized, open-label study. Patients are stratified according to study center and then randomized to 1 of 2 treatment arms.

  • 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: *Mercaptopurine and methotrexate are discontinued during tretinoin administration.

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

PROJECTED ACCRUAL:
Open or close this module Conditions
Conditions: Leukemia
Keywords: adult acute promyelocytic leukemia (M3)
adult acute myeloid leukemia with t(15;17)(q22;q12)
Open or close this module Study Design
Study Type: Interventional
Primary Purpose: Treatment
Study Phase: Phase 3
Interventional Study Model:
Number of Arms:
Masking: None (Open Label)
Allocation: Randomized
Enrollment: 162
Open or close this module Arms and Interventions
Intervention Details:
Drug: arsenic trioxide
Drug: idarubicin
Drug: mercaptopurine
Drug: methotrexate
Drug: mitoxantrone hydrochloride
Drug: tretinoin
Procedure: chemotherapy
Open or close this module Outcome Measures
Primary Outcome Measures:
1. Event-free survival at 2 years
Secondary Outcome Measures:
1. Rate of hematological complete remission
2. Overall survival rate at 2 years
3. Rate of incomplete remission at 2 years
4. Incidence of hematological and non-hematological toxicity episodes during treatment as assessed by CTC-NCI
5. Rate of molecular remission after 3rd consolidation course
6. Assessment of acute promyelocytic leukemia/RARa transcript level reduction after induction and during consolidation
7. Total hospitalization days during therapy
8. Quality-of-life at the end of induction phase and at the end of the 3rd consolidation course
Open or close this module Eligibility
Minimum Age: 18 Years
Maximum Age: 70 Years
Sex: All
Gender Based:
Accepts Healthy Volunteers: No
Criteria:

DISEASE CHARACTERISTICS:

  • Cytologically and morphologically confirmed acute promyelocytic leukemia (PML)
    • Diagnosis must also be confirmed at the genetic level as determined by microspeckled PML nuclear distribution by PGM3 monoclonal antibody and/or PML/RARa fusion by reverse transcriptase-PCR and/or demonstration of t(15;17) by karyotyping
  • Newly diagnosed disease

PATIENT CHARACTERISTICS:

  • WHO performance status 0-2
  • WBC ≤ 10,000/mm³
  • Bilirubin ≤ 3.0 mg/dL
  • Creatinine ≤ 3.0 mg/dL
  • Not pregnant or nursing
  • Fertile patients must use effective contraception
  • No other active malignancy at time of study entry
  • No significant arrhythmias
  • No severe uncontrolled pulmonary or cardiac disease
  • No EKG abnormalities including any of the following:
    • Congenital long QT syndrome
    • History or presence of significant ventricular or atrial tachyarrhythmia
    • Clinically significant resting bradycardia (< 50 beats per minute)
    • QTc > 450 msec
    • Right bundle branch block plus left anterior hemiblock, bifascicular block
  • No other cardiac contraindications for intensive chemotherapy (e.g., LVEF < 50%)
  • No uncontrolled, life-threatening infections
  • No severe psychiatric disorder
  • No HIV positivity

PRIOR CONCURRENT THERAPY:

  • More than 30 days since prior and no other concurrent investigational drugs
Open or close this module Contacts/Locations
Study Officials: Francesco Lo Coco, MD
Study Chair
Azienda Ospadaliera Universitaria Policlinico Tor Vergata
Locations: Italy
Azienda Ospadaliera Universitaria Policlinico Tor Vergata
[Recruiting]
Rome, Italy, 00133
Contact:Contact: Francesco Lo Coco, MD 39-06-2090-3800
Open or close this module IPDSharing
Plan to Share IPD:
Open or close this module References
Links:
Available IPD/Information:
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