The aim of the present EWALL-INO study is to confirm very promising results obtained with a combination of INO and mild chemotherapy in older de novo CD22+ B-ALL patients. For that purpose, safety and efficacy of a weekly INO administration combined to mild-intensity chemotherapy will be evaluated in a cohort of patients aged more than 55 years with newly diagnosed previously untreated Ph-negative (CD22+) BCP-ALL. Conversely to the MDACC miniHCVD-INO study and in order to lower the overall toxicity of the combination, INO will be given as part of the remission induction treatment phase during the first 2 treatment cycles only, in combination with corticosteroid, vincristine, cyclophosphamide and intrathecal prophylaxis only; then, all responding patients will received standard INO-free chemotherapy as consolidation and maintenance.
INO schedule of administration will be as described in the refractory/relapsed INO-VATE study for the first cycle, with sequential day 1/8/15 doses of 0.8, 0.5 and 0.5 mg/m2, respectively. Reduced dose of INO will be used for the second and last cycle (0.5 mg/m2 on day 1/8). This was retained in order: 1. to minimize potential toxicities, including liver disorders and prolonged thrombocytopenia; and 2. to allow delivery of subsequent chemotherapy consolidations cycles.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
130
INO schedule of administration is as follows: * First induction course: 0.8 mg/m² on day 1, 0.5 mg/m² on day 8, and 0.5 mg/m² on day 15 * Second induction course: 0.5 mg/m² on day 1, and 0.5 mg/m² on day 8
CH Amiens sud
Amiens, France
CHU Angers
Angers, France
CH Victor Dupouy
Argenteuil, France
CH cote basque
Bayonne, France
CHU Besançon
Besançon, France
Hopital Avicenne
Bobigny, France
Assessment of overall survival (OS)
The primary objective of the trial is to assess overall survival (OS) observed at 1 year after administration of INO and chemotherapy in older Ph-negative BCP-ALL patients.
Time frame: one year
Assessment of adverse events (AEs)
Type, duration and frequency of AEs up to 3 months of induction course 1 or 2
Time frame: 3 months
Rate of complete remission (CR / CRp)
CR/CRp response rate after INO-based induction course 1 and 2
Time frame: 35 days
Assessment of Minimal residual disease (MRD)
Flow cytometry and Ig-TCR MRD levels, after INO-based induction course 1 and 2 and impact on outcomes
Time frame: 35 days
Rate of early death
Early death (ED) rate at 30, 60 and 100 day from treatment initiation
Time frame: 100 days
Composite measure for Duration of response (DOR), Disease-free survival (DFS) and cumulative incidence of relapse (CIR)
Duration of response (DOR), Disease-free survival (DFS) and cumulative incidence of relapse (CIR)
Time frame: one year
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Hopital Duchenne
Boulogne-sur-Mer, France
CHU Caen
Caen, France
CH Rene Dubois
Cergy-Pontoise, France
CH metropole Savoie_ chambery
Chambéry, France
...and 31 more locations