The hypothesis to be tested is that arm B is tolerable and that the outcome in arm B is better than in arm A.
ID
Bron
Verkorte titel
Aandoening
Acute Myeloid leukemia (AML), RAEB
Ondersteuning
P/a HOVON Data Center
Erasmus MC - Daniel den Hoed
Postbus 5201
3008 AE Rotterdam
Tel: 010 7041560
Fax: 010 7041028
e-mail: hdc@erasmusmc.nl
Koningin Wilhelmina Fonds (KWF)
Genzyme
Onderzoeksproduct en/of interventie
Uitkomstmaten
Primaire uitkomstmaten
Part A:<br>
To determine the feasibility of Clofarabine when given at three possible dose levels together with standard induction cycles I and II in patients with AML/ RAEB with IPSS=>1.5 in a prospective comparison to standard induction cycles I and II without Clofarabine.
<br><br>
Part B:<br>
To evaluate the effect of Clofarabine at the selected feasible dose level when combined with remission induction chemotherapy cycles I and II as regards clinical outcome ("event-free survival") in comparison to remission induction cycles I and II with no addition of Clofarabine in a phase III study.
Achtergrond van het onderzoek
Study phase:
Phase III.
Study objective:
Part A:
To determine the feasibility of Clofarabine when given at three possible dose levels together with standard induction cycles I and II in patients with AML/ RAEB with IPSS=>1.5 in a prospective comparison to standard induction cycles I and II without Clofarabine.
Part B:
To evaluate the effect of Clofarabine at the selected feasible dose level when combined with remission induction chemotherapy cycles I and II as regards clinical outcome ("event-free survival") in comparison to remission induction cycles I and II with no addition of Clofarabine in a phase III study.
Patient population:
Patients with previously untreated AML (except acute promyelocytic leukemia) or MDS RAEB with IPSS => 1.5, age 18-65 years.
Study design:
Part A: Comparative, randomized feasibility study of remission induction chemotherapy combined with Clofarabine at three possible dose levels 10, 15, 20 mg/m2 given intravenously for 5 days.
Part B: Multicenter, phase III study at the selected feasible dose level of Clofarabine in a prospective randomized approach between Clofarabine combined with two induction cycles of chemotherapy versus the same chemotherapy with no addition of Clofarabine.
Duration of treatment:
Expected duration of 2 induction cycles inclusive evaluation is approximately 3 months. Consolidation treatment will take an additional 1-3 months.
All patients will be followed until 10 years after randomization.
Doel van het onderzoek
The hypothesis to be tested is that arm B is tolerable and that the outcome in arm B is better than in arm A.
Onderzoeksopzet
1. At entry;
2. After each induction cycle;
3. After cycle III, autoSCT or alloSCT;
4. During follow up: every 6 months.
Onderzoeksproduct en/of interventie
Patients will be randomized on entry for induction between:
Arm A:
1. Cycle I: idarubicin and conventional dose cytarabine;
2. Cycle II: amsacrine and intermediate dose cytarabine.
Arm B:
1. Cycle I: idarubicin, conventional dose cytarabine and assigned dose of Clofarabine;
2. Cycle II: amsacrine, conventional dose cytarabine and assigned dose Clofarabine.
Publiek
P.O. Box 5201
B. Löwenberg
Rotterdam 3008 AE
The Netherlands
+31 (0)10 4391598
b.lowenberg@erasmusmc.nl
Wetenschappelijk
P.O. Box 5201
B. Löwenberg
Rotterdam 3008 AE
The Netherlands
+31 (0)10 4391598
b.lowenberg@erasmusmc.nl
Belangrijkste voorwaarden om deel te mogen nemen (Inclusiecriteria)
1. Age 18-65 years, inclusive;
2. Subjects with:
A. A cytopathologically confirmed diagnosis of AML according WHO classification (excluding acute promyelocytic leukaemia) or;
B. A diagnosis of refractory anemia with excess of blasts (RAEB) and IPSS score =>1.5 or;
C. Patients with therapy-related AML/RAEB or;
D. Patients with biphenotypic leukemia (Appendices A1 and A2).
3. Adequate renal and hepatic function tests as indicated by the following laboratory values:
A. Serum creatinine =<1.0 mg/dl (=< 88.7 micromol/L); if serum creatinine >1.0 mg/dl (>88.7 micromol/L), then the glomerular filtration rate (GFR) must be >60 ml/min/1.73 m2 as calculated by the Modification of Diet in Renal Disease equation where the predicted GFR (ml/min/1.73 m2) = 186 x (Serum Creatinine in mg/dl)^-1.154 x (age in years)^-0.203 x (0.742 if patient is female) x (1.212 if patient is black).
NOTE: if serum creatinine is measured in micromol/L, recalculate it in mg/dl according to the equation: 1 mg/dl = 88.7 micromol/L) and used above mentioned formula;
B. Serum bilirubin =<1.5 x upper limit of normal (ULN);
C. Aspartate transaminase (AST)/alanine transaminase (ALT) =<2.5 x ULN;
D. Alkaline phosphatase =<2.5 x ULN.
4. WHO performance status 0, 1 or 2 (see Appendix I);
5. Written informed consent.
Belangrijkste redenen om niet deel te kunnen nemen (Exclusiecriteria)
1. Acute promyelocytic leukaemia;
2. Previous treatment for AML or RAEB, except hydroxyurea;
3. Concurrent history active malignancy in two past years prior to diagnosis except for:
A. Basal and squamous cell carcinoma of the skin;
B. In situ carcinoma of the cervix.
4. Concurrent severe and/or uncontrolled medical condition (e.g. uncontrolled diabetes, infection, hypertension, pulmonary disease etcetera);
5. Cardiac dysfunction as defined by:
A. Myocardial infarction within the last 6 months of study entry, or;
B. Reduced left ventricular function with an ejection fraction < 50% as measured by MUGA scan or echocardiogram (another method for measuring cardiac function is acceptable), or;
C. Unstable angina, or;
D. Unstable cardiac arrhythmias.
6. Pregnant or lactating females;
7. Unwilling or not capable to use effective means of birth control.
Opzet
Deelname
Opgevolgd door onderstaande (mogelijk meer actuele) registratie
Geen registraties gevonden.
Andere (mogelijk minder actuele) registraties in dit register
Geen registraties gevonden.
In overige registers
| Register | ID |
|---|---|
| NTR-new | NL2070 |
| NTR-old | NTR2187 |
| Ander register | HOVON : HO102 |
| ISRCTN | ISRCTN wordt niet meer aangevraagd. |