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

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Acute Lymphoblastic Leukemia (ALL) - Philadelphia Chromosome (Ph)-Negative CD22+ B-cell Precursor (BCP)
• Intervention / Treatment: Drug: Inotuzumab ozogamicin (INO)

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.

• Study Type: Interventional
• Enrollment (Estimated): 130
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Assitan KONE; Phone Number: +33 1 39 23 97 75; Email: akone@ch-versailles.fr
• Study Contact Backup: Name: Laure MORISSET; Phone Number: +33 1 39 23 97 85; Email: lmorisset@ch-versailles.fr

Study Locations

• France
  • Amiens, France
    • CH Amiens sud
  • Angers, France
    • CHU Angers
  • Argenteuil, France
    • CH Victor Dupouy
  • Bayonne, France
    • CH Cote Basque
  • Besançon, France
    • CHU Besançon
  • Bobigny, France
    • Hôpital Avicenne
  • Boulogne-sur-Mer, France
    • Hôpital Duchenne
  • Caen, France
    • CHU Caen
  • Cergy-Pontoise, France
    • CH Rene Dubois
  • Chambéry, France
    • CH metropole Savoie_ chambery
  • Clamart, France
    • HIA Percy
  • Clermont-Ferrand, France
    • CHU Clermond Ferrand
  • Créteil, France
    • Hôpital Mondor
  • Dijon, France
    • Hopital Dijon
  • Grenoble, France
    • Chu Grenoble
  • La Réunion, France
    • CHU La Réunion
  • Le Chesnay, France
    • CH Versailles
  • Limoges, France
    • CHU Limoges
  • Lyon, France
    • Centre Léon Bérard
  • Marseille, France
    • IPC
  • Meaux, France
    • CH Meaux
  • Montpellier, France
    • CH Montpellier
  • Nantes, France
    • CHU Nantes
  • Nice, France
    • CHU Nice
  • Nice, France
    • Centre Lacassagne
  • Nîmes, France
    • Chu Nimes
  • Orléans, France
    • CHR Orléans
  • Paris, France
    • Hôpital Necker
  • Paris, France
    • Hopital St Louis
  • Paris, France
    • Hopital St Antoine
  • Pessac, France
    • CHU Haut Leveque
  • Pierre-Bénite, France
    • CH Lyon sud
  • Reims, France
    • CH Reims
  • Rennes, France
    • CHU Pontchaillou
  • Roubaix, France
    • CH Roubaix
  • Rouen, France
    • Centre H Becquerel Rouen
  • Saint-Priest-en-Jarez, France
    • Institut de Cancérologie
  • Strasbourg, France
    • CHU Strasbourg
  • Toulouse, France
    • IUCT Oncopole
  • Valenciennes, France
    • CH Valenciennes
  • Vandœuvre-lès-Nancy, France
    • CHRU Nancy

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 55 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Inotuzumab ozogamicin (INO)	Drug: 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Assessment of overall survival (OS)	The primary objective of the trial is to assess overall survival (OS) observed at 1 year after administration of INO and chemotherapy in older Ph-negative BCP-ALL patients.	one year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Assessment of adverse events (AEs)	Type, duration and frequency of AEs up to 3 months of induction course 1 or 2	3 months
Rate of complete remission (CR / CRp)	CR/CRp response rate after INO-based induction course 1 and 2	35 days
Assessment of Minimal residual disease (MRD)	Flow cytometry and Ig-TCR MRD levels, after INO-based induction course 1 and 2 and impact on outcomes	35 days
Rate of early death	Early death (ED) rate at 30, 60 and 100 day from treatment initiation	100 days
Composite measure for Duration of response (DOR), Disease-free survival (DFS) and cumulative incidence of relapse (CIR)	Duration of response (DOR), Disease-free survival (DFS) and cumulative incidence of relapse (CIR)	one year

Collaborators and Investigators

• Sponsor: Versailles Hospital
• Investigators: Principal Investigator: Patrice CHEVALLIER, MD, Nantes University Hospital

Study record dates

Study Major Dates

• Study Start (Actual): December 28, 2017
• Primary Completion (Actual): May 30, 2023
• Study Completion (Estimated): June 1, 2024

Study Registration Dates

• First Submitted: August 10, 2017
• First Submitted That Met QC Criteria: August 10, 2017
• First Posted (Actual): August 15, 2017

Study Record Updates

• Last Update Posted (Actual): September 6, 2023
• Last Update Submitted That Met QC Criteria: September 4, 2023
• Last Verified: September 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Chromosome Aberrations; Translocation, Genetic; Leukemia; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Lymphoid; Philadelphia Chromosome; Physiological Effects of Drugs; Antineoplastic Agents; Immunologic Factors; Antineoplastic Agents, Immunological; Antibiotics, Antineoplastic; Immunoconjugates; Immunotoxins; Inotuzumab Ozogamicin
• Other Study ID Numbers: P16/11- EWALL INO; 2016-004942-27 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No