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

Acute Lymphoblastic Leukemia Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03441061
• Other study ID #: 2015-0921
• Secondary ID: NCI-2018-0093620
• Status: Recruiting
• Phase: Phase 2
• Start date: February 15, 2018
• Est. completion date: February 28, 2025

Study information

• Verified date: March 2024
• Source: M.D. Anderson Cancer Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Description:

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 40
• Est. completion date: February 28, 2025
• Est. primary completion date: February 28, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Acute Lymphoblastic Leukemia
• B Acute Lymphoblastic Leukemia
• Leukemia
• Leukemia, Lymphoid
• Neoplasm, Residual
• Precursor Cell Lymphoblastic Leukemia-Lymphoma
• Recurrent B Acute Lymphoblastic Leukemia

Intervention

Biological:
• Inotuzumab Ozogamicin
Given IV

Locations

Country	Name	City	State
United States	M D Anderson Cancer Center	Houston	Texas

Sponsors (2)

Lead Sponsor	Collaborator
M.D. Anderson Cancer Center	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Relapse-free survival (RFS)		Up to 4 years
Secondary	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
Secondary	Overall survival		Up to 4 years
Secondary	Minimal residual disease (MRD) negativity rate		Up to 4 years

External Links

•   MD Anderson Cancer Center