To compare event-free survival (EFS) of the experimental treatment arm including ATO/ATRA and idarubicin with standard treatment based on ATRA plus chemotherapy (AIDA regimen).
ID
Source
Brief title
Condition
- Leukaemias
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Event-free survival
Secondary outcome
-Rate of hematological CR after induction
-Rate of early death during induction
-Rate of overall survival (OS) at 2 years
-Rate of cumulative incidence of secondary MDS or AML
-Rate of cumulative incidence of relapse (CIR) at 2 years
-Incidence of hematological and non-hematological toxicity
-Rate of molecular remission after last consolidation cycle
-Assessment of PML/RARA transcript level reduction during treatment
-To investigate differences in the following a priori Quality of Life selected
scales: physical and cognitive functioning as well as fatigue, nausea and
vomiting, constipation and appetite loss
-To investigate differences in the immune reconstitution between the two arms
-Total hospitalization days during therapy and health economic impact
Background summary
Acute promyelocytic leukemia (APL) is a rare subtype of acute myeloid leukemia
(AML) characterized by consistent clinical, morphologic, and genetic features.
APL is often clinically characterized by the presence of coagulation
abnormalities, including disseminated intra vascular coagulation (DIC),
hyperfibrinolysis and unspecific proteolysis. Despite the dramatic progress
achieved in frontline therapy of APL with ATRA plus anthracycline-based
regimens (AIDA), relapses still occur in approximately 20% of the patients.
Moreover, these regimens are associated with significant toxicities due to
severe myelosuppression frequently associated with life-threatening infections
and potentially serious late effects including development of secondary
MDS/AML. A combination of ATO with ATRA shows better survival with significant
lower toxicity rates compared to standard therapy in low/intermediate risk APL
patients. In this trial we intend to perform a trial in high-risk APL patients
comparing standard AIDA based treatment with ATO/ATRA combination with
low-doses idarubicine during induction. We expect less severe toxicity and
treatment-related mortality resulting in an improved outcome for patients in
the experimental arm. Furthermore, from the start of consolidation, these
patients (in contrast to the standard arm) can be treated on an outpatient
basis, which is also considered to be associated with an improved QoL.
Study objective
To compare event-free survival (EFS) of the experimental treatment arm
including ATO/ATRA and idarubicin with standard treatment based on ATRA plus
chemotherapy (AIDA regimen).
Study design
Open label, randomized, prospective muliticenter, multinational phase III
trial.
Intervention
Experimental intervention (Arm A): ATO/ATRA and idarubicin
Control intervention (Arm B): AIDA regimen for high-risk (ATRA plus
chemotherapy)
Study burden and risks
Participation in this study will be associated with extra investigations
compared to standard patient care. It is possible that the patient will
experience different adverse events in comparison to standard care.
Furthermore, patients will be requested to participate in Quality of Life
studies.
Fetscherstr 74
Dresden 01307
DE
Fetscherstr 74
Dresden 01307
DE
Listed location countries
Age
Inclusion criteria
1.Informed consent
2.Women or men with a newly diagnosed APL by cytomorphology, confirmed by molecular analysis
3.Age >= 18 and <= 65 years
4.ECOG performance status 0-3
5.WBC at diagnosis > 10GPt/l
6.Serum total bilirubin <= 3.0 mg/dl (<=51 µmol/l)
7.Serum creatinine <= 3.0 mg/dl (<=260 µmol/l)
8.Women must fulfill at least one of the following criteria in order to be eligible for trial inclusion:
a.Post-menopausal (12 months of natural amenorrhea or 6 months amenorrhea with serum FSH > 40 U/ml)
b.Postoperative (i.e. 6 weeks) after bilateral ovariectomy with or without hysterectomy
c.Continuous and correct application of a contraception method with a Pearl Index of <1% (e.g. implants, depots, oral contraceptives, intrauterine device-IUD)
d.Sexual abstinence
e.Vasectomy of the sexual partner
Exclusion criteria
1.Patients who are not eligible for chemotherapy as per discretion of the treating physician
2.APL secondary to previous radio- or chemotherapy for non-APL disease
3.Other active malignancy at time of study entry (exception: basal-cell carcinoma)
4.Lack of diagnostic confirmation at genetic level
5.Significant arrhythmias, ECG abnormalities:
a.Congenital long QT syndrome
b.History or presence of significant ventricular or atrial tachyarrhythmia
c.Clinically significant resting bradycardia (<50 beats per minute)
d.QTc >500msec on screening ECG for both genders
e.Right bundle branch block plus left anterior hemiblock, bifascicular block
6.Other cardiac contraindications for intensive chemotherapy (L-VEF <50%)
7.Uncontrolled, life-threatening infections
8.Severe non controlled pulmonary or cardiac disease
9.Severe hepatic or renal dysfunction
10.HIV and/or active hepatitis C infection
11.Active multiple sclerosis (patients with inactive MS can be included)
12.Pregnant or breast-feeding patients
13.Allergy to trial medication or excipients in study medication
14.Substance abuse; medical, psychological or social conditions that may interfere with the patients participation in the study or evaluation of the study results
15.Use of other investigational drugs at the time of enrolment or within 30 days before study entry
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2015-001151-68-NL |
| CCMO | NL56512.042.16 |