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

NCT02458014 | Completed Phase 2 FDA Drug

• 2 other identifiers: 2014-0844NCI-2015-01547
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 1

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.

Conditions

Adult Acute Lymphoblastic Leukemia in Complete Remission; B Acute Lymphoblastic Leukemia; Minimal Residual Disease; Philadelphia Chromosome Positive

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (5)

• Event-free survival

  Up to 18 months

• Overall survival (OS)

  Up to 18 months

• MRD negativity rate

  Up to 18 months

• MRD negativity rate after course 1

  Up to 6 weeks

• Incidence of toxicity

  Up to 18 months

Study Arms (1)

Treatment (blinatumomab)

EXPERIMENTAL

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; Other: Laboratory Biomarker Analysis

Interventions

Blinatumomab BIOLOGICAL

Given IV

Also known as: Anti-CD19 x Anti-CD3 Bispecific Monoclonal Antibody, Anti-CD19/Anti-CD3 Recombinant Bispecific Monoclonal Antibody MT103, Blincyto, MEDI-538, MT-103

Treatment (blinatumomab)

Laboratory Biomarker Analysis OTHER

Correlative studies

Treatment (blinatumomab)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

M D Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Publications (2)

• 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.

  PMID: 35713551 DERIVED

• 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.

  PMID: 35622074 DERIVED

Related Links

• M D Anderson Cancer Center

MeSH Terms

Conditions

Burkitt Lymphoma; Neoplasm, Residual

Interventions

blinatumomab; N,N-dicyclohexyl-isoborneol-10-sulfonamide

Condition Hierarchy (Ancestors)

Epstein-Barr Virus Infections; Herpesviridae Infections; DNA Virus Infections; Virus Diseases; Infections; Tumor Virus Infections; Lymphoma, B-Cell; Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Elias Jabbour

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 26, 2015
• First Posted: May 29, 2015
• Study Start: September 14, 2015
• Primary Completion: September 16, 2025
• Study Completion: September 16, 2025
• Last Updated: September 23, 2025

Record last verified: 2025-09

Locations

US (1)