A phase 1 study of inotuzumab ozogamicin in pediatric relapsed/refractory acute lymphoblastic leukemia (ITCC-059 study) | Zendy

Erica Brivio | Zendy; Franco Locatelli | Zendy; Marta LópezYurda | Zendy; Andrea Malone | Zendy; Cristina Díaz de Heredia | Zendy; Bella Bielorai | Zendy; Claudia Rössig | Zendy; Vincent H. J. van der Velden | Zendy; Anneke C. J. Ammerlaan | Zendy; Adriana Thano | Zendy; Inge M. van der Sluis | Zendy; Monique L. den Boer | Zendy; Ying Chen | Zendy; Barbara Sleight | Zendy; Benoît Brethon | Zendy; Karsten Nysom | Zendy; Lucie Šrámková | Zendy; Ingrid Øra | Zendy; Luciana Vinti | Zendy; Christiane ChenSantel | Zendy; C. Michel Zwaan | Zendy

AI Assistant Blog Pricing

Home ZAIA Blog

Open Access

A phase 1 study of inotuzumab ozogamicin in pediatric relapsed/refractory acute lymphoblastic leukemia (ITCC-059 study)

Author(s) -

Erica Brivio,

Franco Locatelli,

Marta LópezYurda,

Andrea Malone,

Cristina Díaz de Heredia,

Bella Bielorai,

Claudia Rössig,

Vincent H. J. van der Velden,

Anneke C. J. Ammerlaan,

Adriana Thano,

Inge M. van der Sluis,

Monique L. den Boer,

Ying Chen,

Barbara Sleight,

Benoît Brethon,

Karsten Nysom,

Lucie Šrámková,

Ingrid Øra,

Luciana Vinti,

Christiane ChenSantel,

C. Michel Zwaan

Publication year - 2020

Publication title -

blood

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 5.515

H-Index - 465

eISSN - 1528-0020

pISSN - 0006-4971

DOI - 10.1182/blood.2020007848

Subject(s) - lymphoblastic leukemia , medicine , refractory (planetary science) , acute lymphocytic leukemia , leukemia , pediatrics , physics , astrobiology

This phase 1 study investigated the recommended phase 2 dose (RP2D) of inotuzumab ozogamicin (InO), a CD22-directed antibody-drug conjugate, in pediatric patients with multiple relapsed/refractory (R/R) CD22+ acute lymphoblastic leukemia (ALL). Patients (age ≥1 year or <18 years) received 3 doses of InO (days 1, 8, and 15) per course. Dose escalation was based on dose-limiting toxicities (DLTs) during course 1. Dose level 1 (DL1) was 1.4 mg/m2 (0.6, 0.4, 0.4 mg/m2) and DL2 was 1.8 mg/m2 (0.8, 0.5, 0.5 mg/m2). Secondary end points included safety, antileukemic activity, and pharmacokinetics. Twenty-five patients (23 evaluable for DLTs) were enrolled. In course 1, the first cohort had 1 of 6 (DL1) and 2 of 5 (DL2) patients who experienced DLTs; subsequent review considered DL2 DLTs to be non-dose-limiting. Dose was de-escalated to DL1 while awaiting protocol amendment to re-evaluate DL2 in a second cohort, in which 0 of 6 (DL1) and 1 of 6 (DL2) patients had a DLT. Twenty-three patients experienced grade 3 to 4 adverse events; hepatic sinusoidal obstruction syndrome was reported in 2 patients after subsequent chemotherapy. Overall response rate after course 1 was 80% (95% confidence interval [CI], 59% to 93%) (20 of 25 patients; DL1: 75% [95% CI, 43% to 95%], DL2: 85% [95% CI, 55% to 98%]). Of the responders, 84% (95% CI, 60% to 97%) achieved minimal residual disease (MRD)-negative complete response, and 12-month overall survival was 40% (95% CI, 25% to 66%). Nine patients received hematopoietic stem cell transplantation or chimeric antigen receptor T cells after InO. InO median maximum concentrations were comparable to simulated adult concentrations. InO was well tolerated, demonstrating antileukemic activity in heavily pretreated children with CD22+ R/R ALL. RP2D was established as 1.8 mg/m2 per course, as in adults. This trial was registered at https://www.clinicaltrialsregister.eu as EUDRA-CT 2016-000227-71.

The content you want is available to Zendy users.

Already have an account? Click here to sign in.

Having issues? You can contact us here

Accelerating Research