Inotuzumab ozogamicin plus chemotherapy in pediatric B-ALL: ITCC-059 trial

The ALL Hub has previously reported results from the phase II ITCC-059 study (EudraCT:2016-000227-71), outlining the safety and efficacy of inotuzumab ozogamicin (InO) as a single agent in pediatric patients with relapsed/refractory B-cell lineage acute lymphoblastic leukemia.

Here, we summarize results from the phase Ib analyses of the ITCC-059 trial investigating InO combined with chemotherapy, published by Pennesi et al.¹ in Haematologica.

Study design¹

• InO (dose 0.8–1.8 mg/m²) was coupled with intrathecal treatment, 20 mg/m² of dexamethasone (two 5-day blocks, subsequently modified), and 1.5 mg/m² of vincristine (Days 3, 10, 17, 24); 29 patients were evaluated for dose-limiting toxicities (DLTs) between May 2020 and April 2022.

Results¹

• Two out of four patients experienced DLT (liver toxicity) at 1.1 mg/m²/cycle
  • InO dosage was deescalated to 0.8 mg/m²/cycle (n = 6) without DLT while a protocol amendment to lower the dexamethasone dose to 10 mg/m² was awaited
  • InO was reescalated to 1.1 mg/m²/cycle (n = 6, 1 DLT) following the amendment; this was followed by 1.4 mg/m²/cycle (n = 3, no DLTs), and 1.8 mg/m²/cycle (n = 7, 1 DLT)

• In total, 24 patients achieved a complete response (overall response rate, 80%), with 22 achieving it after the first cycle with 20 in CR, three in CR with insufficient platelet recovery, and one in complete remission with incomplete blood count recovery
• In total, 66.7% of respondents met the measurable residual disease negativity threshold

• In a fractionated regimen, the recommended phase II dose of InO in combination with vincristine, dexamethasone, and intrathecal treatment was established at 1.8 mg/m²/cycle (1.5 mg/m²/cycle after remission)

Safety¹

• Overall, 24 patients had either aspartate aminotransferase and/or alanine aminotransferase elevation
  • Alanine aminotransferase increased in 23 patients (50% were ≥Grade 3)
  • Aspartate aminotransferase increased in 22 patients; 10 were Grade 3 (33.3%)
  • Seven patients (23.3%) had a bilirubin increase (20% were Grade 1–2 and 3% were Grade 3)