Description:
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.
Title
- Brief Title: Study of Inotuzumab Ozogamicin Combined to Chemotherapy in Older Patients With Philadelphia Chromosome-negative CD22+ B-cell Precursor ALL
- 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
Clinical Trial IDs
- ORG STUDY ID:
P16/11- EWALL INO
- SECONDARY ID:
2016-004942-27
- NCT ID:
NCT03249870
Conditions
- Acute Lymphoblastic Leukemia (ALL) - Philadelphia Chromosome (Ph)-Negative CD22+ B-cell Precursor (BCP)
Interventions
Drug | Synonyms | Arms |
---|
Inotuzumab ozogamicin (INO) | | Inotuzumab ozogamicin (INO) |
Purpose
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.
Trial Arms
Name | Type | Description | Interventions |
---|
Inotuzumab ozogamicin (INO) | Experimental | | - Inotuzumab ozogamicin (INO)
|
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.
Maximum Eligible Age: | N/A |
Minimum Eligible Age: | 55 Years |
Eligible Gender: | All |
Healthy Volunteers: | No |
Primary Outcome Measures
Measure: | Assessment of overall survival (OS) |
Time Frame: | one year |
Safety Issue: | |
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. |
Secondary Outcome Measures
Measure: | Assessment of adverse events (AEs) |
Time Frame: | 3 months |
Safety Issue: | |
Description: | Type, duration and frequency of AEs up to 3 months of induction course 1 or 2 |
Measure: | Rate of complete remission (CR / CRp) |
Time Frame: | 35 days |
Safety Issue: | |
Description: | CR/CRp response rate after INO-based induction course 1 and 2 |
Measure: | Assessment of Minimal residual disease (MRD) |
Time Frame: | 35 days |
Safety Issue: | |
Description: | Flow cytometry and Ig-TCR MRD levels, after INO-based induction course 1 and 2 and impact on outcomes |
Measure: | Rate of early death |
Time Frame: | 100 days |
Safety Issue: | |
Description: | Early death (ED) rate at 30, 60 and 100 day from treatment initiation |
Measure: | Composite measure for Duration of response (DOR), Disease-free survival (DFS) and cumulative incidence of relapse (CIR) |
Time Frame: | one year |
Safety Issue: | |
Description: | Duration of response (DOR), Disease-free survival (DFS) and cumulative incidence of relapse (CIR) |
Details
Phase: | Phase 2 |
Primary Purpose: | Interventional |
Overall Status: | Recruiting |
Lead Sponsor: | Versailles Hospital |
Last Updated
August 11, 2020