Clinical trial NCT03441061: Inotuzumab Ozogamicin in Treating Patients With B-cell Acute Lymphocytic Leukemia With Positive Minimal Residual Disease
Official title: Phase II Study of Inotuzumab Ozogamicin in Patients With B-Cell Lineage Acute Lymphocytic Leukemia With Positive Minimal Residual Disease
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Acute Lymphoblastic Leukemia
B Acute Lymphoblastic Leukemia
Recurrent B Acute Lymphoblastic Leukemia
Lead sponsor: M.D. Anderson Cancer Center
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2018-02-22
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Detailed 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.

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

Primary outcomes:
measure: Relapse-free survival (RFS)
timeFrame: Up to 4 years
Secondary outcomes:
measure: Incidence of adverse events
timeFrame: Up to 4 years
measure: Overall survival
timeFrame: Up to 4 years
measure: Minimal residual disease (MRD) negativity rate
timeFrame: Up to 4 years
Other outcomes:
Locations:
city: Houston
country: United States
facility: M D Anderson Cancer Center
state: Texas
Study officials:
affiliation: M.D. Anderson Cancer Center
name: Elias Jabbour
role: PRINCIPAL_INVESTIGATOR
References:
citation: Shi Z, Zhu Y, Zhang J, Chen B. Monoclonal antibodies: new chance in the management of B-cell acute lymphoblastic leukemia. Hematology. 2022 Dec;27(1):642-652. doi: 10.1080/16078454.2022.2074704.