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

Primary Purpose

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

Status

Recruiting

Phase

Phase 2

Locations

United States

Study Type

Interventional

Intervention

Inotuzumab Ozogamicin

About this trial

This is an interventional treatment trial for Acute Lymphoblastic Leukemia

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

M D Anderson Cancer CenterRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Treatment (inotuzumab ozogamicin)

Arm Description

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.

Outcomes

Primary Outcome Measures

Relapse-free survival (RFS)

Secondary Outcome Measures

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.

Overall survival

Minimal residual disease (MRD) negativity rate

Full Information

NCT ID

NCT03441061

First Posted

February 15, 2018

Last Updated

October 3, 2023

Sponsor

M.D. Anderson Cancer Center

Collaborators

National Cancer Institute (NCI)

1. Study Identification

Unique Protocol Identification Number

NCT03441061

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

Study Type

Interventional

2. Study Status

Record Verification Date

October 2023

Overall Recruitment Status

Recruiting

Study Start Date

February 15, 2018 (Actual)

Primary Completion Date

February 28, 2025 (Anticipated)

Study Completion Date

February 28, 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

M.D. Anderson Cancer Center

Collaborators

National Cancer Institute (NCI)

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

5. 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.

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

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

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

40 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Treatment (inotuzumab ozogamicin)

Arm Type

Experimental

Arm Description

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.

Intervention Type

Biological

Intervention Name(s)

Inotuzumab Ozogamicin

Other Intervention Name(s)

Besponsa, CMC-544, Way 207294, WAY-207294

Intervention Description

Given IV

Primary Outcome Measure Information:

Title

Relapse-free survival (RFS)

Time Frame

Up to 4 years

Secondary Outcome Measure Information:

Title

Incidence of adverse events

Description

Time Frame

Up to 4 years

Title

Overall survival

Time Frame

Up to 4 years

Title

Minimal residual disease (MRD) negativity rate

Time Frame

Up to 4 years

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Elias Jabbour

Organizational Affiliation

M.D. Anderson Cancer Center

Official's Role

Principal Investigator

Facility Information:

Facility Name

M D Anderson Cancer Center

City

Houston

State/Province

Texas

ZIP/Postal Code

77030

Country

United States

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Elias Jabbour

Phone

713-792-4764

ejabbour@mdanderson.org

First Name & Middle Initial & Last Name & Degree

Elias Jabbour

12. IPD Sharing Statement

Citations:

PubMed Identifier

35622074

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.

Results Reference

derived

Links:

URL

https://www.mdanderson.org/

Description

MD Anderson Cancer Center

Learn more about this trial

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

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