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

Minimal Residual Disease Clinical Trial

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT02458014
• Other study ID #: 2014-0844
• Secondary ID: NCI-2015-0154720
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: September 14, 2015
• Est. completion date: September 30, 2024

Study information

• Verified date: February 2024
• Source: M.D. Anderson Cancer Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 36
• Est. completion date: September 30, 2024
• Est. primary completion date: September 30, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Adult Acute Lymphoblastic Leukemia in Complete Remission
• B Acute Lymphoblastic Leukemia
• Leukemia
• Leukemia, Lymphoid
• Minimal Residual Disease
• Neoplasm, Residual
• Philadelphia Chromosome
• Philadelphia Chromosome Positive
• Precursor Cell Lymphoblastic Leukemia-Lymphoma

Intervention

Biological:
• Blinatumomab
Given IV

Other:
• Laboratory Biomarker Analysis
Correlative studies

Locations

Country	Name	City	State
United States	M D Anderson Cancer Center	Houston	Texas

Sponsors (2)

Lead Sponsor	Collaborator
M.D. Anderson Cancer Center	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	From date of treatment start until the date of death or hematologic or extramedullary disease relapse, assessed up to 18 months
Secondary	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).	Up to 18 months
Secondary	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.	Up to 18 months
Secondary	MRD negativity rate	Will be estimated along with the exact 95% confidence interval.	Up to 18 months
Secondary	MRD negativity rate after course 1	Will be estimated along with the exact 95% confidence interval.	Up to 6 weeks
Secondary	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.	Up to 18 months

External Links

•   M D Anderson Cancer Center