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

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.

Sex

All

Minimum age

55 Years

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.

• RESULTChevallier P, Leguay T, Delord M, Salek C, Kim R, Huguet F, Hicheri Y, Wartiovaara-Kautto U, Raffoux E, Cluzeau T, Balsat M, Roth-Guepin G, Tavernier E, Lepretre S, Bilger K, Bergugnat H, Berceanu A, Alexis M, Doubek M, Brissot E, Hunault-Berger M, Lebon D, Turlure P, Chantepie S, Belhabri A, Wickenhauser S, Bastie JN, Cacheux V, Himberlin C, Banos A, Gardin C, Bonnet S, Plantier I, Pica GM, Escoffre-Barbe M, Boissel N, Dombret H, Clappier E, Rousselot P; Group for Research on Adult Acute Lymphoblastic Leukemia (GRAALL) and the European Working Group for Adult Acute Lymphoblastic Leukemia (EWALL); European Working Group for Adult Acute Lymphoblastic Leukemia (EWALL). Inotuzumab Ozogamicin and Low-Intensity Chemotherapy in Older Patients With Newly Diagnosed CD22+ Philadelphia Chromosome-Negative B-Cell Precursor Acute Lymphoblastic Leukemia. J Clin Oncol. 2024 Dec 20;42(36):4327-4341. doi: 10.1200/JCO.24.00490. Epub 2024 Oct 17. PMID 39418626