Blinatumomab in Treating Patients With B-cell Acute Lymphoblastic Leukemia With Minimal Residual Disease

Sponsor

M.D. Anderson Cancer Center (Other)

Overall Status

Active, not recruiting

CT.gov ID

NCT02458014

Collaborator

National Cancer Institute (NCI) (NIH)

Enrollment

Location

Arm

84.5

Anticipated Duration (Months)

0.5

Patients Per Site Per Month

Study Details

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.

Condition or Disease	Intervention/Treatment	Phase
Adult Acute Lymphoblastic Leukemia in Complete Remission B Acute Lymphoblastic Leukemia Minimal Residual Disease Philadelphia Chromosome Positive	Biological: Blinatumomab Other: Laboratory Biomarker Analysis	Phase 2

Detailed Description

PRIMARY OBJECTIVES:

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:

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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

40 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Sep 14, 2015

Anticipated Primary Completion Date :

Sep 30, 2022

Anticipated Study Completion Date :

Sep 30, 2022

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Treatment (blinatumomab) 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.	Biological: Blinatumomab Given IV Other Names: Anti-CD19 x Anti-CD3 Bispecific Monoclonal Antibody Anti-CD19/Anti-CD3 Recombinant Bispecific Monoclonal Antibody MT103 Blincyto MEDI-538 MT-103 Other: Laboratory Biomarker Analysis Correlative studies

Arm

Intervention/Treatment

Experimental: Treatment (blinatumomab)

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.

Biological: Blinatumomab

Given IV

Other Names:

Anti-CD19 x Anti-CD3 Bispecific Monoclonal Antibody

Anti-CD19/Anti-CD3 Recombinant Bispecific Monoclonal Antibody MT103

Blincyto

MEDI-538

MT-103

Other: Laboratory Biomarker Analysis

Correlative studies

Outcome Measures

Primary Outcome Measures

Relapse-free survival (RFS) [From date of treatment start until the date of death or hematologic or extramedullary disease relapse, assessed up to 18 months]
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 [Up to 18 months]
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) [Up to 18 months]
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 [Up to 18 months]
Will be estimated along with the exact 95% confidence interval.
MRD negativity rate after course 1 [Up to 6 weeks]
Will be estimated along with the exact 95% confidence interval.
Incidence of toxicity [Up to 18 months]
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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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