A Phase 2 Study of Inotuzumab Ozogamicin in Children and Young Adults with Relapsed or Refractory CD22+ B-Acute Lymphoblastic Leukemia (B-ALL)

AALL1621 is a group-wide single-arm phase 2 study to evaluate the toxicity profile and preliminary efficacy of inotuzumab ozogamicin (InO) in pediatric patients with CD22-positive B-lymphoblastic leukemia (B-ALL) that is refractory or in second or greater relapse. InO is an antibody-drug conjugate composed of a humanized IgG subtype 4 monoclonal CD22-targeted antibody linked to calicheamicin, a potent anti-tumor antibiotic. InO demonstrated exceptional activity in relapsed or refractory B-ALL in adults. Patients will receive fractionated dosing of InO due to the favorable efficacy and toxicity profile of this administration schedule in adult B-ALL, with dosing on Days 1, 8, and 15 of each 28 day cycle. Those patients whose disease does not meet the definition of treatment failure after Cycle 1 may receive an additional cycle, and those with a complete response (CR) or complete response with incomplete hematologic recovery (CRi) following 2 cycles may receive up to 4 additional cycles of therapy. The primary endpoint is morphologic CR/CRi following one cycle of InO therapy. Secondary endpoints include pharmacokinetics of InO and toxicity monitoring with particular attention to sinusoidal obstruction syndrome (SOS) of the liver, which was the primary significant toxicity observed in previous trials of InO in adult patients. Optional biology studies include evaluation of leukemic blast CD22 site density and splice variants, comparison of minimal residual disease (MRD) detection by flow cytometry with next generation sequencing techniques, evaluation of the impact of InO therapy on B cell development and immune function, and investigation of serum biomarkers associated with SOS.