Acute Lymphoblastic Leukemia (ALL) - Philadelphia Chromosome (Ph)-Negative CD22+ B-cell Precursor (BCP)
Conditions
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: 1. to minimize potential toxicities, including liver disorders and prolonged thrombocytopenia; and 2. to allow delivery of subsequent chemotherapy consolidations cycles.
Interventions
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
Sponsors
Versailles Hospital
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
55 Years to No maximum
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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) |
Countries
France
Contacts
PRINCIPAL_INVESTIGATORPatrice CHEVALLIER, MD
Nantes University Hospital
Outcome results
None listed