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

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

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.

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.