Back to resultsStudy of Inotuzumab Ozogamicin Combined to Chemotherapy in Older Patients With Philadelphia Chromosome-negative CD22+ B-cell Precursor ALL (EWALL-INO)
Primary Purpose
Acute Lymphoblastic Leukemia (ALL) - Philadelphia Chromosome (Ph)-Negative CD22+ B-cell Precursor (BCP)
Status
Active
Phase
Phase 2
Locations
France
Study Type
Interventional
Intervention
Inotuzumab ozogamicin (INO)
Sponsored by
About this trial
This is an interventional treatment trial for Acute Lymphoblastic Leukemia (ALL) - Philadelphia Chromosome (Ph)-Negative CD22+ B-cell Precursor (BCP)
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.
Sites / Locations
- CH Amiens sud
- CHU Angers
- CH Victor Dupouy
- CH cote basque
- CHU Besançon
- Hopital Avicenne
- Hopital Duchenne
- CHU Caen
- CH Rene Dubois
- CH metropole Savoie_ chambery
- HIA Percy
- CHU Clermond Ferrand
- Hopital Mondor
- Hopital Dijon
- CHU Grenoble
- CHU la Reunion
- CH Versailles
- CHU Limoges
- Centre Leon Berard
- IPC
- CH Meaux
- CH Montpellier
- CHU Nantes
- Centre Lacassagne
- CHU Nice
- CHU Nimes
- CHR Orléans
- Hopital Necker
- Hopital St Antoine
- Hopital St Louis
- CHU Haut Leveque
- CH Lyon Sud
- CH Reims
- CHU Pontchaillou
- CH Roubaix
- Centre H Becquerel Rouen
- Institut de cancerologie
- CHU Strasbourg
- IUCT Oncopole
- CH Valenciennes
- CHRU Nancy
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Inotuzumab ozogamicin (INO)
Arm Description
Outcomes
Primary Outcome Measures
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.
Secondary Outcome Measures
Assessment of adverse events (AEs)
Type, duration and frequency of AEs up to 3 months of induction course 1 or 2
Rate of complete remission (CR / CRp)
CR/CRp response rate after INO-based induction course 1 and 2
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
Rate of early death
Early death (ED) rate at 30, 60 and 100 day from treatment initiation
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)
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT03249870
Brief Title
Study of Inotuzumab Ozogamicin Combined to Chemotherapy in Older Patients With Philadelphia Chromosome-negative CD22+ B-cell Precursor ALL
Acronym
EWALL-INO
Official Title
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
Study Type
Interventional
2. Study Status
Record Verification Date
September 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
December 28, 2017 (Actual)
Primary Completion Date
May 30, 2023 (Actual)
Study Completion Date
June 2024 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Versailles Hospital
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
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:
to minimize potential toxicities, including liver disorders and prolonged thrombocytopenia; and
to allow delivery of subsequent chemotherapy consolidations cycles.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Acute Lymphoblastic Leukemia (ALL) - Philadelphia Chromosome (Ph)-Negative CD22+ B-cell Precursor (BCP)
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
130 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Inotuzumab ozogamicin (INO)
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
Inotuzumab ozogamicin (INO)
Intervention Description
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
Primary Outcome Measure Information:
Title
Assessment of overall survival (OS)
Description
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.
Time Frame
one year
Secondary Outcome Measure Information:
Title
Assessment of adverse events (AEs)
Description
Type, duration and frequency of AEs up to 3 months of induction course 1 or 2
Time Frame
3 months
Title
Rate of complete remission (CR / CRp)
Description
CR/CRp response rate after INO-based induction course 1 and 2
Time Frame
35 days
Title
Assessment of Minimal residual disease (MRD)
Description
Flow cytometry and Ig-TCR MRD levels, after INO-based induction course 1 and 2 and impact on outcomes
Time Frame
35 days
Title
Rate of early death
Description
Early death (ED) rate at 30, 60 and 100 day from treatment initiation
Time Frame
100 days
Title
Composite measure for Duration of response (DOR), Disease-free survival (DFS) and cumulative incidence of relapse (CIR)
Description
Duration of response (DOR), Disease-free survival (DFS) and cumulative incidence of relapse (CIR)
Time Frame
one year
10. Eligibility
Sex
All
Minimum Age & Unit of Time
55 Years
Accepts Healthy Volunteers
No
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Patrice CHEVALLIER, MD
Organizational Affiliation
Nantes University Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
CH Amiens sud
City
Amiens
Country
France
Facility Name
CHU Angers
City
Angers
Country
France
Facility Name
CH Victor Dupouy
City
Argenteuil
Country
France
Facility Name
CH cote basque
City
Bayonne
Country
France
Facility Name
CHU Besançon
City
Besançon
Country
France
Facility Name
Hopital Avicenne
City
Bobigny
Country
France
Facility Name
Hopital Duchenne
City
Boulogne-sur-Mer
Country
France
Facility Name
CHU Caen
City
Caen
Country
France
Facility Name
CH Rene Dubois
City
Cergy-Pontoise
Country
France
Facility Name
CH metropole Savoie_ chambery
City
Chambéry
Country
France
Facility Name
HIA Percy
City
Clamart
Country
France
Facility Name
CHU Clermond Ferrand
City
Clermont-Ferrand
Country
France
Facility Name
Hopital Mondor
City
Créteil
Country
France
Facility Name
Hopital Dijon
City
Dijon
Country
France
Facility Name
CHU Grenoble
City
Grenoble
Country
France
Facility Name
CHU la Reunion
City
La Réunion
Country
France
Facility Name
CH Versailles
City
Le Chesnay
Country
France
Facility Name
CHU Limoges
City
Limoges
Country
France
Facility Name
Centre Leon Berard
City
Lyon
Country
France
Facility Name
IPC
City
Marseille
Country
France
Facility Name
CH Meaux
City
Meaux
Country
France
Facility Name
CH Montpellier
City
Montpellier
Country
France
Facility Name
CHU Nantes
City
Nantes
Country
France
Facility Name
Centre Lacassagne
City
Nice
Country
France
Facility Name
CHU Nice
City
Nice
Country
France
Facility Name
CHU Nimes
City
Nîmes
Country
France
Facility Name
CHR Orléans
City
Orléans
Country
France
Facility Name
Hopital Necker
City
Paris
Country
France
Facility Name
Hopital St Antoine
City
Paris
Country
France
Facility Name
Hopital St Louis
City
Paris
Country
France
Facility Name
CHU Haut Leveque
City
Pessac
Country
France
Facility Name
CH Lyon Sud
City
Pierre-Bénite
Country
France
Facility Name
CH Reims
City
Reims
Country
France
Facility Name
CHU Pontchaillou
City
Rennes
Country
France
Facility Name
CH Roubaix
City
Roubaix
Country
France
Facility Name
Centre H Becquerel Rouen
City
Rouen
Country
France
Facility Name
Institut de cancerologie
City
Saint-Priest-en-Jarez
Country
France
Facility Name
CHU Strasbourg
City
Strasbourg
Country
France
Facility Name
IUCT Oncopole
City
Toulouse
Country
France
Facility Name
CH Valenciennes
City
Valenciennes
Country
France
Facility Name
CHRU Nancy
City
Vandœuvre-lès-Nancy
Country
France
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
Study of Inotuzumab Ozogamicin Combined to Chemotherapy in Older Patients With Philadelphia Chromosome-negative CD22+ B-cell Precursor ALL
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