Primary objectives:1.The fesibility of clofarabine when given together with standard prephase chemotehrapy in a prospective comparison to standard prephase chemotherapy (prednison). 2.To evaluate the effect of clofarabin when combined with prephase…
ID
Source
Brief title
Condition
- Leukaemias
- Leukaemias
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
1. Feasiblilty of clofarabine when added to standard phrephase chemotherapy.
2. Event-free survival (EFS) (i.e., time from registration to induction
failure, death or relapse whichever occurs first).
Secondary outcome
- Response
- Overall survival (OS) mesured form the time of registration
- Disease-free interval (duration of the first CR) measured form the time of
achievement of CR to day of relapse or death from any cause (whichever occurs
first).
- Outcome of treatment in relation to minimal residual disease measurements.
- Evaluation of toxicities and treatment related mortality.
Background summary
In this phase III study the drug clofarabine is added to the standard
chemotherapy for remission induction therapy of adults age below 70 years, with
acute lymphoblastic leukemia. The aim of this study is to examine whether the
treatment outcome improves by adding clofarabine. Clofarabine is an effective
drug that, if given as singel medication to the patients with relapsed disease
induces remissions. In this study clofarabine is given in combination with the
standard prephase chemotherapy and subsequently as monotherapy in a distinct
consolidation cycle. In the first part of the study the feasebility of
clofarabine will be examined compared to the treatment without clofarabine in a
randomized design. In the second part of the study the phase III will be done
with the feasible dose level. Minimal residual disease measurements at
previously defined timepoints will be performed to be able to correlate the
effect of therapy.
Study objective
Primary objectives:
1.The fesibility of clofarabine when given together with standard prephase
chemotehrapy in a prospective comparison to standard prephase chemotherapy
(prednison).
2.To evaluate the effect of clofarabin when combined with prephase chemotherapy
and as a single consolidation courase as regards clinical outcome ("event-free
survival") in comparison to prephase / consolidation without clofarabine in a
phase III study.
Secondary objectives:
- To improve the molecular response rate of adult ALL following RI by the
addition of i.v. clofarabine to standard prephaseprephase and consolidation
therapy
- To improve DFS, and OS in adult ALL patients by the addition of i.v.
clofarabine to the
standard prephase and consolidation therapy
- To document safety and toxicity of adding clofarabine to standard prephase
and consolidation therapy in adult ALL
- To assess and compare clinical outcome of patients with and without an
HLA-identical sibling in a donor vs no-donor analysis
Study design
1. Comparative, randomized feasibility study of remission induction
chemotherapy combined with clofarabine.
2. Multicenter, phase III study at the feasible dose level of clofarabin in a
prospective randomised approach.
Intervention
In the experimantal arm intraveniously administered clofarabine will be added
to standard prephase chemotherapy.
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. At each dose level
the decision to stop or escalate will be made bye the DSMB based on a
comparison of DLTs in either arm.
Study burden and risks
The addition of lofarabine can increase the possibility of toxicities. Possibly
not all toxicities are known, although clofarabine is given before and seems to
be tolerated well. Clofaraine causes nausea and alopecia. Further it reduces
the production of blood as other chemotherapy does.
Further toxicities of clofarabine known from previous research are lier
dysfunction.
At time of the normal bone marrow punctions at start a limited amount of extra
bone marrow will be collected via the same needle. this is abouth 10 ml.
For monitoring of Asparaginase activity blood will be taken for during
induction and intensificaion I and II for the young patients en for the older
patients 4 times during consolidatie II. This will be combined with the regular
blood takes, if possible.
De Boelelaan 1117
Amsterdam 1081 HV
NL
De Boelelaan 1117
Amsterdam 1081 HV
NL
Listed location countries
Age
Inclusion criteria
- Patients aged 18 to 70 years inclusive
- Primary previously untreated B or T-lineage ALL (excluding ALL with mature B-cell phenotype, but including Philadelphia positive or BCR-ABL positive ALL) or previously untreated T-LBL (pretreatment with prednisone for 7 days is allowed)
- WHO performance status 0 - 2
- Adequate renal and hepatic function tests as indicated by the following laboratory
values:
- 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)-0.023 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.
- Serum bilirubin <= 1.5 × upper limit of normal (ULN)
- Aspartate transaminase (AST)/alanine transaminase (ALT) <= 2.5 × ULN
- Alkaline phosphatase <= 2.5 × ULN
- Negative pregnancy test at inclusion, if applicable
- Written informed consent
Exclusion criteria
- Mature surface Ig positive B-cell leukemia/lymphoma
- Acute undifferentiated leukemia
- Severe cardiovascular disease (arrhythmias requiring chronic treatment, congestive heart failure or symptomatic ischemic heart disease)
- Severe pulmonary dysfunction (CTCAE grade III-IV)
- Severe neurological or psychiatric disease
- History of active malignancy during the past 5 years with the exception of basal carcinoma of the skin or stage 0 cervical carcinoma
- Active, uncontrolled infection
-Patient known to be HIV-positive
-Patient is a lactating woman
- Any psychological, familial, sociological and geographical condition potentially hampering compliance with the study protocol and follow-up schedule
- Unwilling or not capable to use effective means of birth control (all men, all premenopausal women under the age of 50 need contraception for two years after the last period, and women older than 50 yrs for at least one year)
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 | EUCTR2008-005798-36-NL |
| CCMO | NL27016.078.09 |