Study of Inotuzumab Ozogamicin Combined to Chemotherapy in Older Patients With Philadelphia Chromosome-negative CD22+ B-cell Precursor ALL
- Conditions
- Acute Lymphoblastic Leukemia (ALL) - Philadelphia Chromosome (Ph)-Negative CD22+ B-cell Precursor (BCP)
- Interventions
- Drug: Inotuzumab ozogamicin (INO)
- Registration Number
- NCT03249870
- Lead Sponsor
- Versailles Hospital
- Brief Summary
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.
- Detailed Description
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.
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 130
- Patients aged more than 55 years old,
- With confirmed diagnosis of BCP-ALL according to World Health Organisation (WHO) criteria expressing the CD22 antigen by flow cytometry (20% or more positive blast cells),
- Without central nervous system (CNS) involvement,
- Without BCR-ABL fusion by standard cytogenetics, Fluorescence In Situ Hybridization (FISH) analysis and/or RT-PCR,
- Previously untreated,
- Eligible to intensive chemotherapy, due to general health status,
- ECOG performance status ≤ 2,
- Patients must have the following laboratory values unless considered due to leukemia: AST and ALT ≤ 2.5 x upper the limit of normal (ULN); estimated GFR ≥ 50 mL/min using the MDRD equation; total and direct serum bilirubin ≤ 1.5 x ULN; electrolyte panel within normal ranges for the institution unless attributed to the underlying disease.
- Written informed consent obtained prior to any screening procedures.
- Eligible for National Health Insurance in France.
- Concurrent therapy with any other investigational agent or cytotoxic drug,
- Prior documented chronic liver disease,
- Active Hepatitis B Virus (HBV) or Hepatitis C Virus (HCV) or positive HIV serology,
- Female patients who are pregnant or breast feeding or patients of childbearing potential not willing to use a double barrier method of contraception during the study and for 3 months following the last dose of maintenance.
- Male patients whose sexual partner(s) are women of childbearing potential who are not willing to use a double barrier method of contraception, one of which includes a condom, during the study and for 3 months following the last dose of maintenance.
- Any of concurrent severe and/or uncontrolled medical condition, which could compromise participation in the study.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Inotuzumab ozogamicin (INO) Inotuzumab ozogamicin (INO) -
- Primary Outcome Measures
Name Time Method Assessment of overall survival (OS) one year 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.
- Secondary Outcome Measures
Name Time Method Composite measure for Duration of response (DOR), Disease-free survival (DFS) and cumulative incidence of relapse (CIR) one year Duration of response (DOR), Disease-free survival (DFS) and cumulative incidence of relapse (CIR)
Assessment of adverse events (AEs) 3 months Type, duration and frequency of AEs up to 3 months of induction course 1 or 2
Rate of complete remission (CR / CRp) 35 days CR/CRp response rate after INO-based induction course 1 and 2
Assessment of Minimal residual disease (MRD) 35 days Flow cytometry and Ig-TCR MRD levels, after INO-based induction course 1 and 2 and impact on outcomes
Rate of early death 100 days Early death (ED) rate at 30, 60 and 100 day from treatment initiation
Trial Locations
- Locations (41)
Hopital Mondor
🇫🇷Créteil, France
CHR Orléans
🇫🇷Orléans, France
Hopital St Louis
🇫🇷Paris, France
CHU Angers
🇫🇷Angers, France
CH Amiens sud
🇫🇷Amiens, France
CH Victor Dupouy
🇫🇷Argenteuil, France
CH cote basque
🇫🇷Bayonne, France
CHU Besançon
🇫🇷Besançon, France
CHU Caen
🇫🇷Caen, France
Hopital Avicenne
🇫🇷Bobigny, France
Hopital Duchenne
🇫🇷Boulogne-sur-Mer, France
CH Rene Dubois
🇫🇷Cergy-Pontoise, France
HIA Percy
🇫🇷Clamart, France
CH metropole Savoie_ chambery
🇫🇷Chambéry, France
CHU Clermond Ferrand
🇫🇷Clermont-Ferrand, France
Hopital Dijon
🇫🇷Dijon, France
CHU Grenoble
🇫🇷Grenoble, France
Centre Leon Berard
🇫🇷Lyon, France
CHU la Reunion
🇫🇷La Réunion, France
CH Versailles
🇫🇷Le Chesnay, France
Centre Lacassagne
🇫🇷Nice, France
CHU Limoges
🇫🇷Limoges, France
IPC
🇫🇷Marseille, France
CH Meaux
🇫🇷Meaux, France
CHU Nantes
🇫🇷Nantes, France
CHU Nice
🇫🇷Nice, France
CHU Nimes
🇫🇷Nîmes, France
CH Montpellier
🇫🇷Montpellier, France
Hopital Necker
🇫🇷Paris, France
CHU Haut Leveque
🇫🇷Pessac, France
Hopital St Antoine
🇫🇷Paris, France
CH Lyon Sud
🇫🇷Pierre-Bénite, France
CHU Pontchaillou
🇫🇷Rennes, France
CH Reims
🇫🇷Reims, France
Institut de cancerologie
🇫🇷Saint-Priest-en-Jarez, France
CH Roubaix
🇫🇷Roubaix, France
Centre H Becquerel Rouen
🇫🇷Rouen, France
IUCT Oncopole
🇫🇷Toulouse, France
CHU Strasbourg
🇫🇷Strasbourg, France
CH Valenciennes
🇫🇷Valenciennes, France
CHRU Nancy
🇫🇷Vandœuvre-lès-Nancy, France