Inotuzumab Ozogamicin in Treating Patients With B-cell Acute Lymphocytic Leukemia With Positive Minimal Residual Disease

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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Phase II Study of Inotuzumab Ozogamicin in Patients With B-Cell Lineage Acute Lymphocytic Leukemia With Positive Minimal Residual Disease

Conditions
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Acute Lymphoblastic Leukemia, B Acute Lymphoblastic Leukemia, Recurrent B Acute Lymphoblastic Leukemia

Intervention / Treatment
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* Biological: Inotuzumab Ozogamicin


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment (inotuzumab ozogamicin)<br>Patients receive inotuzumab ozogamicin 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. | Biological: Inotuzumab Ozogamicin<br>* Given IV<br>* Other names: WAY-207294;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Relapse-free survival (RFS) |  | Up to 4 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of adverse events | Will continuously monitor treatment-related toxicities using the Bayesian approach of Thall, Simon, Estey. For the purpose of toxicity monitoring, toxicities are defined as any treatment-related grade 3 or 4 non-hematologic adverse events occurring any time during the trial. | Up to 4 years | 
| Overall survival |  | Up to 4 years | 
| Minimal residual disease (MRD) negativity rate |  | Up to 4 years |