Post-Transplant Inotuzumab Ozogamicin for Acute Lymphoblastic Leukemia

Background: The curative potential of allogeneic transplant (alloHCT) in patients with acute lymphoblastic leukemia (ALL) is hampered by relapse; the major cause of treatment failure. Risk factors for relapse include measurable residual disease (MRD) before or after alloHCT, transplantation in second complete remission (CR) or beyond, and reduced intensity conditioning (RIC) regimens. In ALL patients, relapse rates range from 30% to 50%, with most relapses occurring within the first year after alloHCT. After relapse, options for disease control are limited, and consequently overall survival is poor. Post-alloHCT maintenance may reduce MRD, provide time for graft-versus-leukemia to develop, and ultimately decrease relapse rates and prolong leukemia-free-survival. Inotuzumab ozogamicin (INO) is an anti-CD22 monoclonal antibody bound to calicheamicin which has significant activity against relapsed ALL. INO gained regulatory approval for the treatment of relapsed/refractory ALL based on a randomized phase 3 trial that showed an overall CR rate of 81% in the INO arm as compared to 29% in the standard arm. With the hypothesis that low-dose INO will be safe and will reduce the relapse rates, we are conducting a phase I/II study using this approach as post-alloHCT maintenance therapy. Methods: Eligibility included patients aged 16-75 who have undergone alloHCT for CD22+ALL in complete remission, have a high risk for relapse after alloHCT (MRD before or after alloHCT, transplantation, in second complete remission (CR) or beyond, reduced intensity conditioning (RIC) regimen used, lymphoid blast crisis of chronic myeloid leukemia, or Ph-like ALL), have adequate graft and organ function, are between day 40 and 100 post-alloHCT, do not have active grade III/IV GVHD or any active GVHD of the liver, and have no history of VOD. The primary objective of this phase I clinical trial is to define a post-alloHCT maximum tolerated dose (MTD) of INO. Secondary objectives include describing the safety profile of INO post-alloHCT, determining the rate of veno-occlusive disease in this setting, evaluating non-relapse mortality (NRM), disease free survival (DFS) and overall survival (OS) at 1 year post-alloHCT and 1 year post-last dose INO, determining the incidence of myeloid toxicity and secondary graft failure, and determining if INO at these doses are effective at eradicating MRD in this cohort of patients. Pre-treatment tests include a bone marrow biopsy and aspirate to assess