Clinical Trials /

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

NCT03249870

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.

Related Conditions:
  • B-Cell Acute Lymphoblastic Leukemia
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

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

DrugSynonymsArms
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

NameTypeDescriptionInterventions
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

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