The hypothesis to be tested in the phase II part is that arm B is feasible. The hypothesis to be tested in the phase III part is that the outcome in arm B is better than in arm A.
ID
Bron
Verkorte titel
Aandoening
Acute Lymphoblastic Leukemia (ALL)
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
Onderzoeksproduct en/of interventie
Uitkomstmaten
Primaire uitkomstmaten
1. Phase II part: To determine the feasibility of adding i.v. clofarabine to standard prephase therapy (followed by induction chemotherapy);<br>
2. Phase III part: To improve EFS in adult ALL patients by the addition of i.v. clofarabine to prephase and consolidation therapy .
Achtergrond van het onderzoek
Study phase: Phase II/III.
Study objective:
Phase II: To determine the feasibility of i.v. clofarabine given prior to standard induction chemotherapy as part of pre-phase.
Phase III: To improve event free survival by adding i.v. clofarabine to prephase and consolidation therapy
Patient population: Patients with previously untreated ALL, age 18-70 years.
Study design:
Phase II: Comparative, randomized feasibility study (dose-finding) of clofarabine chemotherapy at three possible dose levels 15, 20, or 30 mg/m2.
Phase III: Multicenter study at the selected feasible dose level of clofarabine in a prospective randomized approach between clofarabine combined with pre-phase therapy and in an extra consolidation cycle versus the same chemotherapy without addition of clofarabine.
Duration of treatment:
Expected duration of 32 months, maintenance therapy of 24 months inclusive.
All patients will be followed until 10 years after randomization.
Doel van het onderzoek
The hypothesis to be tested in the phase II part is that arm B is feasible.
The hypothesis to be tested in the phase III part is that the outcome in arm B is better than in arm A.
Onderzoeksopzet
1. At entry;
2. Pre-phase;
3. Induction;
4. Consolidation;
5. Interphase;
6. Intensification;
7. Allo-SCT;
8. Maintenance;
9. Follow-up (every 6 months.
Onderzoeksproduct en/of interventie
In the experimental arm B intravenously administered clofarabine will be added to standard prephase chemotherapy and used in an extra consolidation cycle. Arm A is the standard arm. The study starts at a dose level of 20 mg/m2, and if possible escalating to 30 mg/m2. If 20 mg/m2 is not feasible we will study 15 mg/m2.
Publiek
P.O. Box 5201
J.J. Cornelissen
Rotterdam 3008 AE
The Netherlands
+31 (0)10 4391598 or +31 (0)10 4391367
j.cornelissen@erasmusmc.nl
Wetenschappelijk
P.O. Box 5201
J.J. Cornelissen
Rotterdam 3008 AE
The Netherlands
+31 (0)10 4391598 or +31 (0)10 4391367
j.cornelissen@erasmusmc.nl
Belangrijkste voorwaarden om deel te mogen nemen (Inclusiecriteria)
1. Patients aged 18 to 70 years inclusive;
2. Primary previously untreated B or T-lineage ALL (excluding -ALL with mature B-cell phenotype, but including Philadelphia positive or BCR-ABL positive ALL);
3. Adequate renal and hepatic function tests as indicated by the following laboratory values:
A. Serum creatinine ¡Ü1.0 mg/dl (¡Ü 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)-0.023 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 ¡Ü 1.5 ¡Á upper limit of normal (ULN);
C. Aspartate transaminase (AST)/alanine transaminase (ALT) ¡Ü 2.5 ¡Á ULN;
D. Alkaline phosphatase ¡Ü 2.5 ¡Á ULN.
4. WHO performance status 0 ¨C 2;
5. Negative pregnancy test at inclusion, if applicable;
6. Written informed consent.
Belangrijkste redenen om niet deel te kunnen nemen (Exclusiecriteria)
1. Mature surface Ig positive B-cell leukemia/lymphoma;
2. Acute undifferentiated leukemia;
3. Severe cardiovascular disease (arrhythmias requiring chronic treatment, congestive heart failure or symptomatic ischemic heart disease);
4. Severe pulmonary dysfunction (CTCAE grade III-IV, see appendix D);
5. Severe neurological or psychiatric disease;
6. History of active malignancy during the past 5 years with the exception of basal carcinoma of the skin or stage 0 cervical carcinoma;
7. Active, uncontrolled infection;
8. Patient known to be HIV-positive;
9. Patient is a lactating woman;
10. Any psychological, familial, sociological and geographical condition potentially hampering compliance with the study protocol and follow-up schedule;
11. 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 | NL1890 |
| NTR-old | NTR2004 |
| Ander register | EudraCT 2008-005798-36 : Ho100 |
| ISRCTN | ISRCTN wordt niet meer aangevraagd. |