EWALL-INO: Study of Inotuzumab Ozogamicin Combined to Chemotherapy in Older Patients With Philadelphia Chromosome-negative CD22+ B-cell Precursor ALL
Study Details
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2 |
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:
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to minimize potential toxicities, including liver disorders and prolonged thrombocytopenia; and
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to allow delivery of subsequent chemotherapy consolidations cycles.
Study Design
Arms and Interventions
| 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
|
Outcome Measures
Primary Outcome Measures
- Assessment of overall survival (OS) [one year]
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) [3 months]
Type, duration and frequency of AEs up to 3 months of induction course 1 or 2
- Rate of complete remission (CR / CRp) [35 days]
CR/CRp response rate after INO-based induction course 1 and 2
- Assessment of Minimal residual disease (MRD) [35 days]
Flow cytometry and Ig-TCR MRD levels, after INO-based induction course 1 and 2 and impact on outcomes
- Rate of early death [100 days]
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) [one year]
Duration of response (DOR), Disease-free survival (DFS) and cumulative incidence of relapse (CIR)
Eligibility Criteria
Criteria
Inclusion Criteria:
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Patients aged more than 55 years old,
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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),
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Without central nervous system (CNS) involvement,
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Without BCR-ABL fusion by standard cytogenetics, Fluorescence In Situ Hybridization (FISH) analysis and/or RT-PCR,
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Previously untreated,
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Eligible to intensive chemotherapy, due to general health status,
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ECOG performance status ≤ 2,
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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.
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Written informed consent obtained prior to any screening procedures.
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Eligible for National Health Insurance in France.
Exclusion Criteria:
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Concurrent therapy with any other investigational agent or cytotoxic drug,
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Prior documented chronic liver disease,
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Active Hepatitis B Virus (HBV) or Hepatitis C Virus (HCV) or positive HIV serology,
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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.
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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.
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Any of concurrent severe and/or uncontrolled medical condition, which could compromise participation in the study.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | CH Amiens sud | Amiens | France | ||
| 2 | CHU Angers | Angers | France | ||
| 3 | CHU Besançon | Besançon | France | ||
| 4 | Hopital Avicenne | Bobigny | France | ||
| 5 | Hopital Duchenne | Boulogne-sur-Mer | France | ||
| 6 | CHU Caen | Caen | France | ||
| 7 | CH metropole Savois_ chambery | Chambéry | France | ||
| 8 | HIA Percy | Clamart | France | ||
| 9 | CHU Clermond Ferrand | Clermont-Ferrand | France | ||
| 10 | Hopital Mondor | Créteil | France | ||
| 11 | Hopital Dijon | Dijon | France | ||
| 12 | CHU Grenoble | Grenoble | France | ||
| 13 | CH Versailles | Le Chesnay | France | ||
| 14 | CHU Limoges | Limoges | France | ||
| 15 | Centre Leon Berard | Lyon | France | ||
| 16 | IPC | Marseille | France | ||
| 17 | CH Meaux | Meaux | France | ||
| 18 | CH Montpellier | Montpellier | France | ||
| 19 | CHU Nantes | Nantes | France | ||
| 20 | Centre Lacassagne | Nice | France | ||
| 21 | CHU Nice | Nice | France | ||
| 22 | CHR Orléans | Orléans | France | ||
| 23 | Hopital Necker | Paris | France | ||
| 24 | Hopital St Antoine | Paris | France | ||
| 25 | Hopital St Louis | Paris | France | ||
| 26 | CHU Haut Leveque | Pessac | France | ||
| 27 | CH Lyon Sud | Pierre-Bénite | France | ||
| 28 | CH Reims | Reims | France | ||
| 29 | CH Roubaix | Roubaix | France | ||
| 30 | Centre H Becquerel Rouen | Rouen | France | ||
| 31 | Institut de cancerologie | Saint-Priest-en-Jarez | France | ||
| 32 | CHU Strasbourg | Strasbourg | France | ||
| 33 | IUCT Oncopole | Toulouse | France | ||
| 34 | CH Valenciennes | Valenciennes | France | ||
| 35 | CHRU Nancy | Vandœuvre-lès-Nancy | France |
Sponsors and Collaborators
- Versailles Hospital
Investigators
- Principal Investigator: Patrice CHEVALLIER, MD, Nantes University Hospital
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- P16/11- EWALL INO
- 2016-004942-27