E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Philadelphia chromosome (Ph)-negative CD22+ B-cell Precursor (BCP) Acute Lymphoblastic Leukemia (ALL) |
Leucémie Aiguë Lymphoblastique (LAL) |
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E.1.1.1 | Medical condition in easily understood language |
Acute Lymphoblastic Leukemia (ALL) |
Leucémie Aiguë Lymphoblastique (LAL) |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10000845 |
E.1.2 | Term | Acute lymphoblastic leukemia |
E.1.2 | System Organ Class | 100000012958 |
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E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
Assess overall survival (OS) observed at 1 year after administration of INO and chemotherapy in older Ph-negative BCP-ALL patients.
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Evaluer la survie globale (OS) observée à 1 an après l'administration de l'INO et de la chimiothérapie chez des patients âgés atteints de LAL BCP Ph-CD22+ et non préalablement traités. |
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E.2.2 | Secondary objectives of the trial |
- Overall survival after censoring patients who will receive subsequent anti-leukemic treatment (for instance, allogeneic SCT or blinatumomab) at the start of this subsequent treatment; - Type, duration and frequency of AEs up to 3 months of induction course 1 or 2; - CR/CRp response rate after INO-based induction course 1 and 2; - Flow cytometry and Ig-TCR MRD levels, after INO-based induction course 1 and 2 and impact on outcomes; - Centralized ALL genomic characterization; - Early death (ED) rate at 30, 60 and 100 day from treatment initiation; Duration of response (DOR), disease-free survival (DFS) and cumulative incidence of relapse (CIR).
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- OS après avoir censuré les patients qui recevront un traitement anti-leucémique ultérieur (par exemple, transplantation de cellules souches allogéniques ou blinatumomab) au début de ce traitement ultérieur; - Type, durée et fréquence des évènements indésirables (EI) jusqu'à 3 mois post-induction (cycle 1 e 2) ; - Taux de rémission complète (RC) et RC avec récupération plaquettaire incomplète (RCp) post-induction (cycle 1 e 2) ; - Niveaux de MRD en biologie moléculaire Ig-TCR et en cytométrie de flux post-induction (cycle 1 e 2) et impact sur les résultats; - Caractérisation génomique des LAL et impact sur les résultats; - Taux de mortalité précoce (MP) à 30, 60 et 100 jours après l'initiation du traitement; - Durée de la réponse (DOR), survie sans maladie (DFS) et incidence cumulée de la rechute (CIR). |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Patients aged more than 55 years old, - With confirmed diagnosis of BCP-ALL according to 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, 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. |
- Tout patient âgé de plus de 55 ans, - Avec un diagnostic confirmé de BCP-LAL selon les critères de l'OMS, exprimant l'antigène CD22 analysé par cytométrie en flux (>=20% de la population blastique) - Sans atteinte du système nerveux central (SNC) - Sans fusion BCR-ABL analysée par cytogénétique standard, analyse FISH et / ou RT-PCR, - Non préalablement traité, - Eligible à une chimiothérapie intensive, - ECOG performance status ≤ 2, - Les patients doivent en outre : - Avoir les valeurs de laboratoire suivantes, sauf si elles sont considérées comme étant dues à la leucémie : ASAT et ALAT ≤ 2,5 x la limite normale supérieure (LNS); clearance de la créatinine ≥ 50 ml/min; bilirubine sérique totale et directe ≤ 1,5 x LNS. - Avoir signé un consentement éclairé de participation à l’étude après délai de réflexion et ce avant tout début de procédure de l’étude. - Etre affilié(e) à un régime de sécurité social (en France). |
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E.4 | Principal exclusion criteria |
- Concurrent therapy with any other investigational agent or cytotoxic drug, - Prior documented chronic liver disease, - Active HBV or HCV hepatitis 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 study drug. - 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, - Any of concurrent severe and/or uncontrolled medical condition, which could compromise participation in the study. |
- Traitement concomitant avec toute autre molécule expérimentale ou médicament cytotoxique, - Maladie du foie chronique documentée antérieurement, - Hépatite active connue liée au VHB ou au VHC ou sérologie HIV positive, - Femmes enceintes ou qui allaitent, - Femmes ou hommes en âge de procréer qui ne sont pas disposés à utiliser une méthode de contraception efficace pendant l'étude et pendant les 3 mois suivant la dernière dose du médicament à l'étude. - Toute affection concomitante grave et / ou incontrôlée, qui pourrait compromettre la participation à l'étude. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Overall survival, defined by the time between day+1 of induction therapy until date of death or last follow-up, will be assessed by the 1-year Kaplan-Meier estimate. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
The time frame between day+1 of induction therapy until date of death or last follow-up (one year maximum). |
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E.5.2 | Secondary end point(s) |
- DFS is defined in responding patients (CR/CRp) by the time between the day of CR/CRp documentation until date of relapse, death or last follow-up. - DOR is defined by the time between the day of CR/CRp documentation until relapse, or last follow-up. - CIR is defined by the time between the day of CR/CRp documentation until relapse, or last follow-up considering deaths in first CR/CRp as competing events. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
The time frame between the day of CR/CRp documentation until date of relapse, death or last follow-up. |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 1 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 35 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 5 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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The last visit of the last patient undergoing the trial. |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 4 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 4 |