Back to resultsBlinatumomab in Treating Patients With B-cell Acute Lymphoblastic Leukemia With Minimal Residual Disease
Primary Purpose
Adult Acute Lymphoblastic Leukemia in Complete Remission, B Acute Lymphoblastic Leukemia, Minimal Residual Disease
Status
Active
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Blinatumomab
Laboratory Biomarker Analysis
Sponsored by
About this trial
This is an interventional treatment trial for Adult Acute Lymphoblastic Leukemia in Complete Remission
Eligibility Criteria
Inclusion Criteria:
- Patients with B-lineage acute lymphocytic leukemia (ALL) in hematologic complete remission (CR) with molecular failure (i.e., had never achieved an MRD-negativity status before blinatumomab) 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 1 x 10^-4 (0.01%) by multicolor flow cytometry and/or by next generation sequencing (NGS)
- Patients with B-lineage ALL in hematologic complete remission (CR) with molecular failure (i.e., had never achieved an MRD-negativity status before blinatumomab) 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 1 x 10-4 (0.01%) by multicolor flow cytometry and/or by next generation sequencing (NGS)
- Performance status of 0, 1, or 2
- Creatinine clearance >= 30 ml/minute
- Bilirubin less than or equal to 3.0 mg/dL
- No active or co-existing malignancy with life expectancy less than 12 months
- Patients with Philadelphia chromosome positive (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 PCR of 0.1% and above (International Scale)
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 and 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 Center
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Treatment (blinatumomab)
Arm Description
Patients receive blinatumomab IV continuously on days 1-28. Treatment repeats every 6 weeks for up to 5 courses in the absence of disease progression or unacceptable toxicity. Patients who do not proceed with stem cell transplantation may receive blinatumomab IV maintenance therapy with one cycle every 3 months for up to 4 cycles. Patients who remain in MRD remission for 3 months and then become MRD positive again can be retreated following the same treatment plan previously received.
Outcomes
Primary Outcome Measures
Relapse-free survival (RFS)
RFS will be estimated using the method of Kaplan and Meier. Will compute the Bayesian posterior probability. As a secondary analysis, will perform a competing risk analysis treating stem cell transplant as a competing event for RFS. In addition, will assess the RFS in the subgroup of patients with minimal residual disease (MRD) positivity in at least marrow complete remission (CR) 2 beyond, or in the subgroup of patients with and without allogenic stem cell transplant (ASCT), if permitted by the sample size. Landmark analysis may be performed to assess the difference in RFS between patients with or without receiving ASCT, if permitted by the sample size.
Secondary Outcome Measures
Event-free survival
Defined as RFS in addition to lack of achievement of negative MRD status after 2 cycles of blinatumomab (events will include death, lack of response after 2 cycles, and loss of response/progression, including MRD recurrence).
Overall survival (OS)
OS will be estimated using the method of Kaplan and Meier. Will assess OS in the subgroup of patients with MRD positivity in at least marrow CR 2 beyond; or in the subgroup of patients with and without ASCT, if permitted by the sample size. Landmark analysis may be performed to assess the difference in OS between patients with or without receiving ASCT, if permitted by the sample size.
MRD negativity rate
Will be estimated along with the exact 95% confidence interval.
MRD negativity rate after course 1
Will be estimated along with the exact 95% confidence interval.
Incidence of toxicity
All treated patients are included in the safety analysis set. The adverse events will be summarized by organ type, grade and attribution to study treatment.
Full Information
NCT ID
NCT02458014
First Posted
May 26, 2015
Last Updated
August 24, 2023
Sponsor
M.D. Anderson Cancer Center
Collaborators
National Cancer Institute (NCI)
1. Study Identification
Unique Protocol Identification Number
NCT02458014
Brief Title
Blinatumomab in Treating Patients With B-cell Acute Lymphoblastic Leukemia With Minimal Residual Disease
Official Title
Phase II Study of Blinatumomab in Patients With B-Cell Lineage Acute Lymphocytic Leukemia With Positive Minimal Residual Disease
Study Type
Interventional
2. Study Status
Record Verification Date
August 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
September 14, 2015 (Actual)
Primary Completion Date
September 30, 2024 (Anticipated)
Study Completion Date
September 30, 2024 (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
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
This phase II trial studies how well blinatumomab works in treating patients with B-cell acute lymphoblastic leukemia whose disease is in remission (causes no symptoms or signs) but is still present in a small number of cells in the body (minimal residual disease). Immunotherapy with monoclonal antibodies, such as blinatumomab, may induce changes in the body's immune system and may interfere with the ability of tumor cells to grow and spread.
Detailed Description
PRIMARY OBJECTIVES:
I. To evaluate the clinical efficacy of blinatumomab in patients B-cell acute lymphoblastic leukemia in complete morphologic remission with positive minimal residual disease (MRD) in terms of relapse-free survival (RFS).
SECONDARY OBJECTIVES:
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 blinatumomab in this setting.
OUTLINE:
Patients receive blinatumomab intravenously (IV) continuously on days 1-28. Treatment repeats every 6 weeks for up to 5 cycles in the absence of disease progression or unacceptable toxicity. Patients who do not proceed with stem cell transplantation may receive blinatumomab IV maintenance therapy with one cycle every 3 months for up to 4 cycles. Patients who remain in MRD remission for 3 months and then become MRD positive again can be retreated following the same treatment plan previously received.
After completion of study treatment, patients are followed up every 6 months.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Adult Acute Lymphoblastic Leukemia in Complete Remission, B Acute Lymphoblastic Leukemia, Minimal Residual Disease, Philadelphia Chromosome Positive
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
36 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Treatment (blinatumomab)
Arm Type
Experimental
Arm Description
Patients receive blinatumomab IV continuously on days 1-28. Treatment repeats every 6 weeks for up to 5 courses in the absence of disease progression or unacceptable toxicity. Patients who do not proceed with stem cell transplantation may receive blinatumomab IV maintenance therapy with one cycle every 3 months for up to 4 cycles. Patients who remain in MRD remission for 3 months and then become MRD positive again can be retreated following the same treatment plan previously received.
Intervention Type
Biological
Intervention Name(s)
Blinatumomab
Other Intervention Name(s)
Anti-CD19 x Anti-CD3 Bispecific Monoclonal Antibody, Anti-CD19/Anti-CD3 Recombinant Bispecific Monoclonal Antibody MT103, Blincyto, MEDI-538, MT-103
Intervention Description
Given IV
Intervention Type
Other
Intervention Name(s)
Laboratory Biomarker Analysis
Intervention Description
Correlative studies
Primary Outcome Measure Information:
Title
Relapse-free survival (RFS)
Description
RFS will be estimated using the method of Kaplan and Meier. Will compute the Bayesian posterior probability. As a secondary analysis, will perform a competing risk analysis treating stem cell transplant as a competing event for RFS. In addition, will assess the RFS in the subgroup of patients with minimal residual disease (MRD) positivity in at least marrow complete remission (CR) 2 beyond, or in the subgroup of patients with and without allogenic stem cell transplant (ASCT), if permitted by the sample size. Landmark analysis may be performed to assess the difference in RFS between patients with or without receiving ASCT, if permitted by the sample size.
Time Frame
From date of treatment start until the date of death or hematologic or extramedullary disease relapse, assessed up to 18 months
Secondary Outcome Measure Information:
Title
Event-free survival
Description
Defined as RFS in addition to lack of achievement of negative MRD status after 2 cycles of blinatumomab (events will include death, lack of response after 2 cycles, and loss of response/progression, including MRD recurrence).
Time Frame
Up to 18 months
Title
Overall survival (OS)
Description
OS will be estimated using the method of Kaplan and Meier. Will assess OS in the subgroup of patients with MRD positivity in at least marrow CR 2 beyond; or in the subgroup of patients with and without ASCT, if permitted by the sample size. Landmark analysis may be performed to assess the difference in OS between patients with or without receiving ASCT, if permitted by the sample size.
Time Frame
Up to 18 months
Title
MRD negativity rate
Description
Will be estimated along with the exact 95% confidence interval.
Time Frame
Up to 18 months
Title
MRD negativity rate after course 1
Description
Will be estimated along with the exact 95% confidence interval.
Time Frame
Up to 6 weeks
Title
Incidence of toxicity
Description
All treated patients are included in the safety analysis set. The adverse events will be summarized by organ type, grade and attribution to study treatment.
Time Frame
Up to 18 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Patients with B-lineage acute lymphocytic leukemia (ALL) in hematologic complete remission (CR) with molecular failure (i.e., had never achieved an MRD-negativity status before blinatumomab) 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 1 x 10^-4 (0.01%) by multicolor flow cytometry and/or by next generation sequencing (NGS)
Patients with B-lineage ALL in hematologic complete remission (CR) with molecular failure (i.e., had never achieved an MRD-negativity status before blinatumomab) 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 1 x 10-4 (0.01%) by multicolor flow cytometry and/or by next generation sequencing (NGS)
Performance status of 0, 1, or 2
Creatinine clearance >= 30 ml/minute
Bilirubin less than or equal to 3.0 mg/dL
No active or co-existing malignancy with life expectancy less than 12 months
Patients with Philadelphia chromosome positive (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 PCR of 0.1% and above (International Scale)
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 and 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
12. IPD Sharing Statement
Citations:
PubMed Identifier
35713551
Citation
Jabbour EJ, Short NJ, Jain N, Jammal N, Jorgensen J, Wang S, Wang X, Ohanian M, Alvarado Y, Kadia T, Sasaki K, Garris R, Garcia-Manero G, Ravandi F, Kantarjian HM. Blinatumomab is associated with favorable outcomes in patients with B-cell lineage acute lymphoblastic leukemia and positive measurable residual disease at a threshold of 10-4 and higher. Am J Hematol. 2022 Sep;97(9):1135-1141. doi: 10.1002/ajh.26634. Epub 2022 Jun 24.
Results Reference
derived
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
http://www.mdanderson.org
Description
M D Anderson Cancer Center
Learn more about this trial
Blinatumomab in Treating Patients With B-cell Acute Lymphoblastic Leukemia With Minimal Residual Disease
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