A Randomized Trial Assessing the Roles of AraC in Newly Diagnosed APL Promyelocytic Leukemia (APL)
A Randomized Trial Assessing the Roles of AraC in Newly Diagnosed Acute Promyelocytic Leukemia (APL)
The first purpose of this randomized trial will be to compare the best treatment group of APL 93 trial (ATRA with early introduction of anthracycline-AraC chemotherapy, followed by 2 consolidation anthracycline-AraC courses and maintenance combining continuous chemotherapy and intermittent ATRA) to the same regimen, but without AraC. It is hoped that the investigational arm, with anthracycline alone chemotherapy (without AraC), will have reduced toxicity without increasing the incidence of relapse, by comparison with a classical induction/consolidation anthracycline-AraC regimen
Thus :
the main end point for this first randomization is relapse at 2 years secondary end points are : complete remission rate ; survival and event free survival at 2 years, and quality-adjusted survival (Q-TWiST).
2) Because patients with initial WBC counts > 10000/mm3 (ie very high counts for APL) appear to remain at relatively high risk of relapse even with the current reference treatment, they will not be included in this trial that assesses the reduction of chemotherapy. On the contrary: i) they will all receive the standard chemotherapy (best treatment group of APL 93 trial);
Thus :
the main end point for this second randomization is relapse at 2 years secondary end points are : survival and event free survival at 2 years 3)Elderly patients with initial WBC ≤ 10000/m3 will receive consolidation chemotherapy without AraC during the first chemotherapy course, and reduced doses of AraC during the second and third course, followed by G-CSF.
Study Overview
Detailed Description
All patients will receive induction treatment with ATRA and a first chemotherapy course, followed by two consolidation chemotherapy courses and maintenance with continuous low dose chemotherapy and intermittent ATRA. Initial stratification will be based on age and WBC count.
Patients aged 60 years with initial WBC 10 00 will all receive the reference AraC+ group (Group A ) (no randomization).
Patients with initial WBC > 10000/mm3 will initially all be treated according to the AraC+ group.
Patients > 60 years and with initial WBC ≤ 10000/mm3) will be only registered, without randomization (Group D) and will receive the reference AraC+ group ,but without AraC during the first chemotherapy course ,and with reduced doses of AraC during the second and third course, followed by G-CSF. .
Study Type
Enrollment (Actual)
Phase
- Phase 3
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
- Child
- Adult
- Older Adult
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- diagnosis of APL based on morphological grounds, and which will have to be confirmed by presence of t(15;17) and/or PML-RARα rearrangement (if RT-PCR for APL cannot be performed at your center, send fresh cells to Prof.C.Chomienne, Centre Hayem, Hopital St.Louis, 1 av. Claude Vellefaux, 75475 PARIS or keep frozen RNA [not frozen cells, as the RNA yield for PML-RAR is often poor in those cells]).
- untreated patient
- no contraindication to intensive chemotherapy (especially cardiac contraindication to daunorubicin)
- in female patients : absence of pregnancy and adequate contraceptive method (due to teratogenetic effects of ATRA in early pregnancy)
- written informed consent.
Exclusion Criteria:
- patients already treated
- patients with contraindication to intensive chemotherapy, especially cardiac contraindication to daunorubicin
- in female patients : pregnancy or absence of adequate contraceptive methods
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
|---|---|
|
No Intervention: A
Patients aged ≤ 60 years and with initial WBC ≤ 10000/mm3 Induction treatment a) ATRA and chemotherapy ATRA 45 mg/m2/d until hematological CR first intensive chemotherapy course : DNR 60 mg/m2/d during 3 days AraC 200 mg/m2/d during 7 days 2) Consolidation treatment
Consists of the combination of continuous low dose chemotherapy and intermittent ATRA, during 2 years
|
|
|
Experimental: B
Patients aged ≤ 60 years and with initial WBC ≤ 10000/mm3 (Group B) Same treatment as Group A but without AraC.
|
Ommit ARAC in the chemotherapy
Other Names:
|
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No Intervention: C
CNS prophylaxis : consists of 5 intrathecal (IT) injections of MTX 15mg and AraC 50 mg (12 mg/m2 maximum 15 mg, and 30mg/m2, maximum 50 mg, respectively, in children) + depomedrol IT. I 3) Maintenance treatment |
|
|
No Intervention: D
Patients aged >60 years and initial WBC ≤ 10000/mm3 Induction treatment a) ATRA and chemotherapy ATRA 45 mg/m2/d until hematological CR first intensive chemotherapy course : DNR 60 mg/m2/d during 3 days (intravenous bolus injection) NO ARA C DURING THIS FIRST COURSE 2) Consolidation treatment
|
Ommit ARAC in the chemotherapy
Other Names:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
|---|---|
|
for patients with initial WBC counts > 10000/mm3 - the main end point for this second randomization is relapse at 2 years
Time Frame: 2 years
|
2 years
|
Secondary Outcome Measures
Outcome Measure |
Time Frame |
|---|---|
|
secondary end points are : complete remission rate ; survival and event free survival at 2 years, and quality-adjusted survival (Q-TWiST). secondary end points are : survival and event free survival at 2 years
Time Frame: 2 years
|
2 years
|
Collaborators and Investigators
Collaborators
Investigators
- Principal Investigator: pierre fenaux, mD, Assistance Publique - Hôpitaux de Paris
Publications and helpful links
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Estimate)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Neoplasms by Histologic Type
- Neoplasms
- Leukemia, Myeloid
- Leukemia, Myeloid, Acute
- Leukemia
- Leukemia, Promyelocytic, Acute
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Anti-Infective Agents
- Antiviral Agents
- Antimetabolites, Antineoplastic
- Antimetabolites
- Antineoplastic Agents
- Immunosuppressive Agents
- Immunologic Factors
- Cytarabine
Other Study ID Numbers
- APL2000
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