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

NCT ID: NCT03249870

Last Updated: 2023-09-06

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE2
• Total Enrollment: 130 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-12-28
• Study Completion Date: 2024-06-30

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.

Conditions

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

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Inotuzumab ozogamicin (INO)

Group Type: EXPERIMENTAL

Inotuzumab ozogamicin (INO)

Intervention Type: DRUG

INO schedule of administration is as follows:

• First induction course: 0.8 mg/m² on day 1, 0.5 mg/m² on day 8, and 0.5 mg/m² on day 15
• Second induction course: 0.5 mg/m² on day 1, and 0.5 mg/m² on day 8

Interventions

Inotuzumab ozogamicin (INO)

INO schedule of administration is as follows:

• First induction course: 0.8 mg/m² on day 1, 0.5 mg/m² on day 8, and 0.5 mg/m² on day 15
• Second induction course: 0.5 mg/m² on day 1, and 0.5 mg/m² on day 8

Intervention Type: DRUG

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.

• Minimum Eligible Age: 55 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Versailles Hospital

OTHER

Sponsor Role: lead

Responsible Party

Patrice Chevallier

MD, PhD

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Patrice CHEVALLIER, MD

Role: PRINCIPAL_INVESTIGATOR

Nantes University Hospital

Locations

CH Amiens sud

Amiens, , France

CHU Angers

Angers, , France

CH Victor Dupouy

Argenteuil, , France

CH cote basque

Bayonne, , France

CHU Besançon

Besançon, , France

Hopital Avicenne

Bobigny, , France

Hopital Duchenne

Boulogne-sur-Mer, , France

CHU Caen

Caen, , France

CH Rene Dubois

Cergy-Pontoise, , France

CH metropole Savoie_ chambery

Chambéry, , France

HIA Percy

Clamart, , France

CHU Clermond Ferrand

Clermont-Ferrand, , France

Hopital Mondor

Créteil, , France

Hopital Dijon

Dijon, , France

CHU Grenoble

Grenoble, , France

CHU la Reunion

La Réunion, , France

CH Versailles

Le Chesnay, , France

CHU Limoges

Limoges, , France

Centre Leon Berard

Lyon, , France

IPC

Marseille, , France

CH Meaux

Meaux, , France

CH Montpellier

Montpellier, , France

CHU Nantes

Nantes, , France

Centre Lacassagne

Nice, , France

CHU Nice

Nice, , France

CHU Nimes

Nîmes, , France

CHR Orléans

Orléans, , France

Hopital Necker

Paris, , France

Hopital St Antoine

Paris, , France

Hopital St Louis

Paris, , France

CHU Haut Leveque

Pessac, , France

CH Lyon Sud

Pierre-Bénite, , France

CH Reims

Reims, , France

CHU Pontchaillou

Rennes, , France

CH Roubaix

Roubaix, , France

Centre H Becquerel Rouen

Rouen, , France

Institut de cancerologie

Saint-Priest-en-Jarez, , France

CHU Strasbourg

Strasbourg, , France

IUCT Oncopole

Toulouse, , France

CH Valenciennes

Valenciennes, , France

CHRU Nancy

Vandœuvre-lès-Nancy, , France

Countries

France

References

Chevallier 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.

Reference Type: DERIVED

PMID: 39418626 (View on PubMed)

Other Identifiers

2016-004942-27

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

P16/11- EWALL INO

Identifier Type: -

Identifier Source: org_study_id