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
Trial Snapshot
- Phase
- Phase 2
- Status
- Completed
- Sponsor
- Enrollment
- 131
- Locations
- 41
- Primary Endpoint
- Assessment of overall survival (OS)
Study Overview
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.
Study Design
- Study Type
- Interventional
- Allocation
- Na
- Intervention Model
- Single Group
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 55 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
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.
Arms & Interventions
Inotuzumab ozogamicin (INO)
Intervention: Inotuzumab ozogamicin (INO) (Drug)
Outcomes
Primary Outcomes
Assessment of overall survival (OS)
Time Frame: 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 Outcomes
- Composite measure for Duration of response (DOR), Disease-free survival (DFS) and cumulative incidence of relapse (CIR)(one year)
- Assessment of adverse events (AEs)(3 months)
- Rate of complete remission (CR / CRp)(35 days)
- Assessment of Minimal residual disease (MRD)(35 days)
- Rate of early death(100 days)
Investigators
Patrice Chevallier
MD, PhD
Nantes University Hospital