Description:
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.
Title
- Brief Title: 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
Clinical Trial IDs
- ORG STUDY ID:
2015-0921
- SECONDARY ID:
NCI-2018-00936
- SECONDARY ID:
2015-0921
- NCT ID:
NCT03441061
Conditions
- Acute Lymphoblastic Leukemia
- B Acute Lymphoblastic Leukemia
- Recurrent B Acute Lymphoblastic Leukemia
Interventions
Drug | Synonyms | Arms |
---|
Inotuzumab Ozogamicin | Besponsa, CMC-544, Way 207294, WAY-207294 | Treatment (inotuzumab ozogamicin) |
Purpose
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.
Trial Arms
Name | Type | Description | Interventions |
---|
Treatment (inotuzumab ozogamicin) | Experimental | 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. | |
Eligibility 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).
- 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 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.
- 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
Maximum Eligible Age: | N/A |
Minimum Eligible Age: | 18 Years |
Eligible Gender: | All |
Healthy Volunteers: | No |
Primary Outcome Measures
Measure: | Relapse-free survival (RFS) |
Time Frame: | Up to 4 years |
Safety Issue: | |
Description: | |
Secondary Outcome Measures
Measure: | Incidence of adverse events |
Time Frame: | Up to 4 years |
Safety Issue: | |
Description: | 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. |
Measure: | Overall survival |
Time Frame: | Up to 4 years |
Safety Issue: | |
Description: | |
Measure: | Minimal residual disease (MRD) negativity rate |
Time Frame: | Up to 4 years |
Safety Issue: | |
Description: | |
Details
Phase: | Phase 2 |
Primary Purpose: | Interventional |
Overall Status: | Recruiting |
Lead Sponsor: | M.D. Anderson Cancer Center |
Last Updated
March 8, 2021