No registrations found.
ID
Source
Brief title
Health condition
Acute Lymphoblastic Leukemia (ALL)
Sponsors and support
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
Intervention
Outcome measures
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.
Background summary
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.
Study objective
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.
Study design
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.
Intervention
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.
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
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
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.
Design
Recruitment
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 |
|---|---|
| NTR-new | NL1890 |
| NTR-old | NTR2004 |
| Other | EudraCT 2008-005798-36 : Ho100 |
| ISRCTN | ISRCTN wordt niet meer aangevraagd. |