|- candidate number||6446|
|- NTR Number||NTR2004|
|- ISRCTN||ISRCTN wordt niet meer aangevraagd.|
|- Date ISRCTN created|
|- date ISRCTN requested|
|- Date Registered NTR||10-sep-2009|
|- Secondary IDs||Ho100 EudraCT 2008-005798-36|
|- Public Title||Clofarabine added to prephase and consolidation therapy in acute lymphoblastic leukemia in adults.|
|- Scientific Title||Clofarabine added to prephase and consolidation therapy in acute lymphoblastic leukemia in adults.|
|- ACRONYM||HOVON 100 ALL|
|- hypothesis||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.
|- Healt Condition(s) or Problem(s) studied||Acute Lymfatic Leukemia (ALL)|
|- Inclusion criteria||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.
|- Exclusion criteria||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.
|- mec approval received||yes|
|- multicenter trial||yes|
|- Type||2 or more arms, randomized|
|- planned startdate ||10-jan-2009|
|- planned closingdate||12-jan-2015|
|- Target number of participants||340|
|- Interventions||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. |
|- Primary outcome||1. Phase II part: To determine the feasibility of adding i.v. clofarabine to standard prephase therapy (followed by induction chemotherapy);|
2. Phase III part: To improve EFS in adult ALL patients by the addition of i.v. clofarabine to prephase and consolidation therapy .
|- Secondary outcome||Phase III part:|
1. To improve the molecular response rate of adult ALL following RI by the addition of i.v. clofarabine to standard prephase and consolidation therapy;
2. To improve DFS, and OS in adult ALL patients by the addition of i.v. clofarabine to the standard prephase and consolidation therapy;
3. To document safety and toxicity of adding clofarabine to standard prephase and consolidation therapy in adult ALL;
4. To assess and compare clinical outcome of patients with and without an HLA-identical sibling in a donor vs no-donor analysis.
|- Timepoints||1. At entry;|
9. Follow-up (every 6 months.
|- Trial web site||www.hovon.nl|
|- CONTACT FOR PUBLIC QUERIES||Prof. Dr. J.J. Cornelissen|
|- CONTACT for SCIENTIFIC QUERIES||Prof. Dr. J.J. Cornelissen|
|- Sponsor/Initiator ||HOVON Data Center|
(Source(s) of Monetary or Material Support)
|Genzyme Corporation, Koningin Wilhelmina Fonds (KWF), Medac, HOVON|
|- Brief summary||Study phase: Phase II/III.|
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.
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.
|- Main changes (audit trail)|
|- RECORD||10-sep-2009 - 12-okt-2009|