Inotuzumab Ozogamicin in Treating Patients With B-cell Acute Lymphocytic Leukemia With Positive Minimal Residual Disease
Study Details
Study Description
Brief 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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2 |
Detailed Description
PRIMARY OBJECTIVE:
- 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:
- 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.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Treatment (inotuzumab ozogamicin) 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
Given IV
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Relapse-free survival (RFS) [Up to 4 years]
Secondary Outcome Measures
- Incidence of adverse events [Up to 4 years]
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.
- Overall survival [Up to 4 years]
- Minimal residual disease (MRD) negativity rate [Up to 4 years]
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Patients with B-lineage ALL in hematologic complete remission (CR) with molecular failure (i.e., had never achieved an MRD-negativity status before inotuzumab ozogamicin) or had a molecular relapse (i.e., 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 a value of at least of 10^-4 (0.01%) by multicolor flow cytometry, PCR and/or next-generation sequencing (NGS).
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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.
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Patients with Philadelphia chromosome (Ph)+ ALL can be enrolled in CR1 or CR2 and beyond. A tyrosine kinase inhibitor (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 a level of at least 1x10^-4 (0.01%) by multicolor flow cytometry and/or by NGS.
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Performance status of 0, 1, or 2
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Creatinine clearance >= 15 ml/min
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Bilirubin < 1.5 X upper limit of normal (ULN)
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Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) < 3 X ULN
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No active or co-existing malignancy with life expectancy less than 12 months
Exclusion Criteria:
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Pregnant or nursing women
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Known to be human immunodeficiency virus positive (HIV+)
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Active and uncontrolled disease/infection as judged by the treating physician
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Unable or unwilling to sign the consent form
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Active central nervous system (CNS) or extramedullary disease
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Monoclonal antibodies therapy within 2 weeks before study entry
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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
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | M D Anderson Cancer Center | Houston | Texas | United States | 77030 |
Sponsors and Collaborators
- M.D. Anderson Cancer Center
- National Cancer Institute (NCI)
Investigators
- Principal Investigator: Elias Jabbour, M.D. Anderson Cancer Center
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- 2015-0921
- NCI-2018-00936
- 2015-0921