Study of Inotuzumab Ozogamicin Combined to Chemotherapy in Older Patients With Philadelphia Chromosome-negative CD22+ B-cell Precursor ALL (EWALL-INO)

Versailles Hospital

Status and phase

Active, not recruiting

Phase 2

Conditions

Acute Lymphoblastic Leukemia (ALL) - Philadelphia Chromosome (Ph)-Negative CD22+ B-cell Precursor (BCP)

Treatments

Drug: Inotuzumab ozogamicin (INO)

Study type

Interventional

Funder types

Other

Identifiers

NCT03249870

2016-004942-27 (EudraCT Number)

P16/11- EWALL INO

Details and patient eligibility

About

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.

Full 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:

to minimize potential toxicities, including liver disorders and prolonged thrombocytopenia; and
to allow delivery of subsequent chemotherapy consolidations cycles.

Enrollment

130 estimated patients

Sex

All

Ages

55+ years old

Volunteers

No Healthy Volunteers

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.