inotuzumab ozogamicin in treating patients with b-cell acute lymphocytic leukemia with positive minimal residual disease

Conditions: Acute Lymphoblastic Leukemia; B Acute Lymphoblastic Leukemia; Recurrent B Acute Lymphoblastic Leukemia

Summary: this phase ii trial studies how well inotuzumab ozogamicin works in treating patients with b-cell acute lymphocytic leukemia with positive minimal residual disease. inotuzumab ozogamicin is a monoclonal antibody called inotuzumab linked to a toxic agent called ozogamicin. inotuzumab ozogamicin attaches to b cell-specific cd22 cancer cells in a targeted way and kills them.

primary objective: i. to evaluate the clinical efficacy of inotuzumab ozogamicin in patients b-cell acute lymphoblastic leukemia (all) in complete morphologic remission with positive minimal residual disease (mrd) in terms of relapse-free survival (rfs). secondary objective: i. to evaluate other efficacy endpoints such as overall survival and mrd negativity rate by flow cytometry and/or polymerase chain reaction (pcr) overall and after the first cycle, as well as safety of inotuzumab ozogamicin in this setting. outline: patients receive inotuzumab ozogamicin intravenously (iv) over 1 hour on days 1 and 8. treatment repeats every 21-28 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity. after completion of study treatment, patients are followed up at 30 day and then periodically every 6 months.

Eligibility criteria:
inclusion criteria: * patients with b-lineage all in hematologic complete remission (cr) with molecular failure (ie, had never achieved an mrd-negativity status before inotuzumab ozogamicin) or had a molecular relapse (ie, became mrd positive after having been mrd negative) starting at any time point after 3 months of frontline therapy. molecular disease or minimal residual disease is defined by any level of measurable residual disease identified by multicolor flow cytometry, pcr and/or next-generation sequencing (ngs). * patients with b-lineage all in at least marrow cr in salvage 1 and beyond with mrd failure at any time point after 1 month of salvage therapy are allowed, including patients who received prior allogeneic stem cell transplantation. * patients with ph+ all can be enrolled in cr1 or cr2 and beyond. a tki will be added at the discretion of the treating physician. mrd for these patients will be defined by either 1.) a ratio of bcr-abl1 to abl1 by pcr of ≥ 0.01% according to the international scale for patients with p210 transcript or a ratio of bcr-abl1 to abl1 by pcr of ≥ 0.01% for patients with non-p210 transcripts, or 2.) detectable mrd at any level of measurable residual disease identified by multicolor flow cytometry and/or by ngs. * performance status of 0, 1, or 2 * creatinine clearance \>= 15 ml/min * bilirubin \< 1.5 x upper limit of normal (uln) * aspartate aminotransferase (ast) or alanine aminotransferase (alt) \< 3 x uln * no active or co-existing malignancy with life expectancy less than 12 months exclusion criteria: * pregnant or nursing women * known to be human immunodeficiency virus positive (hiv+) * active and uncontrolled disease/infection as judged by the treating physician * unable or unwilling to sign the consent form * active central nervous system (cns) or extramedullary disease * monoclonal antibodies therapy within 2 weeks before study entry * radiotherapy or cancer chemotherapy (except for intrathecal prophylaxis and/or low-dose maintenance therapy such as vinca alkaloids, mercaptopurine, methotrexate, steroids) or any investigational drug within 2 weeks before study entry