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 MedDRA version: 17.0 Level: LLT Classification code 10000845 Term: Acute lymphoblastic leukemia System Organ Class: 100000004864 MedDRA version: 17.0 Level: LLT Classification code 10043028 Term: T-lymphoblastic lymphoma (Kiel Classification) System Organ Class: 100000004864
Conditions
Interventions
Trade Name: Evoltra 1 mg/ml concentrate for solution for infusion
Product Name: Evoltra
Pharmaceutical Form: Concentrate for solution for infusion
Sponsors
HOVON Foundation
Eligibility
Sex/Gender
All
Inclusion criteria
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 prednisolone 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 Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 326 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 50
Exclusion criteria
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, see appendix D) - 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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Phase II part - To determine the feasibility of adding i.v. clofarabine to standard prephase therapy (followed by induction chemotherapy) Phase III part - To improve EFS in adult ALL patients by the addition of i.v. clofarabine to the standard prephase and consolidation therapy ;Secondary Objective: - To improve the molecular response rate of adult ALL following RI by the addition of i.v. clofarabine to standard prephasepreophase 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 ;Primary end point(s): Phase II of the study: Feasibility (i.e. defined as less than 10% increase in DLT (e.g. from 20% to 30%) and 5% increase in TRM in arm B compared to arm A Phase III of the study: Event free survival (i.e. time from registration until no CR on protocol treatment, relapse or death in 1st CR, whichever comes first);Timepoint(s) of evaluation of this end point: At entry: The investigations before start of treatment should be no older than 14 days prior to randomization unless otherwise noted in the following part During induction, consolidation, intensification, allo-SCT, interphase and maintenance therapy During follow up | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): - MRD level following induction chemotherapy - MRD level prior start of maintenance - Blood blast clearance (corticosteroid sensitivity)(day 8 of prephase) - Chemosensitivity (day 15 counted from start prephase therapy) - Hematological response - Disease free survival (hematologically; i.e. time from CR until relapse or death, whichever comes first) - Disease free survival (molecularly); i.e. time from molecular CR until molecular relapse or death (whichever comes first) - Overall survival, measured from the time of registration. Patients still alive or lost to follow up are censored at the date they were last known to be alive. - Adverse events - Relapse as from start of maintenance - Incidence of objectively diagnosed symptomatic thromboembolic events - Influence of ALL (treatment) on plasma coagulation markers ;Timepoint(s) of evaluation of this end point: At entry: The investigations before start of treatment should be no older than 14 days prior to randomization unless otherwise noted in the following part During induction, consolidation, intensification, allo-SCT, interphase and maintenance therapy During follow up | — |
Countries
Belgium, Croatia, France, Netherlands, Portugal
Contacts
Public ContactClinical Trial Center, HDC
HOVON
Outcome results
None listed