Clinical trial NCT03249870: Study of Inotuzumab Ozogamicin Combined to Chemotherapy in Older Patients With Philadelphia Chromosome-negative CD22+ B-cell Precursor ALL
Official title: A Phase 2 Study of Inotuzumab Ozogamicin (INO) Combined to Chemotherapy in Older Patients With Philadelphia Chromosome-negative CD22+ B-cell Precursor Acute Lymphoblastic Leukemia
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Acute Lymphoblastic Leukemia (ALL) - Philadelphia Chromosome (Ph)-Negative CD22+ B-cell Precursor (BCP)
Lead sponsor: Versailles Hospital
Sponsor class: OTHER
First posted: 2017-08-15
Enrollment: 130
Sex: ALL
Minimum age (years): 55
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: Inclusion Criteria:

* 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.

Exclusion Criteria:

* 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.

Primary outcomes:
measure: Assessment of overall survival (OS)
timeFrame: one year
Secondary outcomes:
measure: Assessment of adverse events (AEs)
timeFrame: 3 months
measure: Rate of complete remission (CR / CRp)
timeFrame: 35 days
measure: Assessment of Minimal residual disease (MRD)
timeFrame: 35 days
measure: Rate of early death
timeFrame: 100 days
measure: Composite measure for Duration of response (DOR), Disease-free survival (DFS) and cumulative incidence of relapse (CIR)
timeFrame: one year
Other outcomes:
Locations:
city: Amiens
country: France
facility: CH Amiens sud
city: Angers
country: France
facility: CHU Angers
city: Argenteuil
country: France
facility: CH Victor Dupouy
city: Bayonne
country: France
facility: CH cote basque
city: Besançon
country: France
facility: CHU Besançon
city: Bobigny
country: France
facility: Hopital Avicenne
city: Boulogne-sur-Mer
country: France
facility: Hopital Duchenne
city: Caen
country: France
facility: CHU Caen
city: Cergy-Pontoise
country: France
facility: CH Rene Dubois
city: Chambéry
country: France
facility: CH metropole Savoie_ chambery
city: Clamart
country: France
facility: HIA Percy
city: Clermont-Ferrand
country: France
facility: CHU Clermond Ferrand
city: Créteil
country: France
facility: Hopital Mondor
city: Dijon
country: France
facility: Hopital Dijon
city: Grenoble
country: France
facility: CHU Grenoble
city: La Réunion
country: France
facility: CHU la Reunion
city: Le Chesnay
country: France
facility: CH Versailles
city: Limoges
country: France
facility: CHU Limoges
city: Lyon
country: France
facility: Centre Leon Berard
city: Marseille
country: France
facility: IPC
city: Meaux
country: France
facility: CH Meaux
city: Montpellier
country: France
facility: CH Montpellier
city: Nantes
country: France
facility: CHU Nantes
city: Nice
country: France
facility: Centre Lacassagne
city: Nice
country: France
facility: CHU Nice
city: Nîmes
country: France
facility: CHU Nimes
city: Orléans
country: France
facility: CHR Orléans
city: Paris
country: France
facility: Hopital Necker
city: Paris
country: France
facility: Hopital St Antoine
city: Paris
country: France
facility: Hopital St Louis
city: Pessac
country: France
facility: CHU Haut Leveque
city: Pierre-Bénite
country: France
facility: CH Lyon Sud
city: Reims
country: France
facility: CH Reims
city: Rennes
country: France
facility: CHU Pontchaillou
city: Roubaix
country: France
facility: CH Roubaix
city: Rouen
country: France
facility: Centre H Becquerel Rouen
city: Saint-Priest-en-Jarez
country: France
facility: Institut de cancerologie
city: Strasbourg
country: France
facility: CHU Strasbourg
city: Toulouse
country: France
facility: IUCT Oncopole
city: Valenciennes
country: France
facility: CH Valenciennes
city: Vandœuvre-lès-Nancy
country: France
facility: CHRU Nancy
Study officials:
affiliation: Nantes University Hospital
name: Patrice CHEVALLIER, MD
role: PRINCIPAL_INVESTIGATOR
References: