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

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ClinicalTrials.gov Identifier: NCT02458014
Recruitment Status : Recruiting
First Posted : May 29, 2015
Last Update Posted : May 24, 2019
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
M.D. Anderson Cancer Center

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:

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.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 40 participants
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 : September 14, 2015
Estimated Primary Completion Date : September 30, 2020


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




Primary Outcome Measures :
  1. Relapse-free survival (RFS) [ Time Frame: 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 :
  1. Event-free survival [ Time Frame: 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).

  2. Overall survival (OS) [ Time Frame: 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.

  3. MRD negativity rate [ Time Frame: Up to 18 months ]
    Will be estimated along with the exact 95% confidence interval.

  4. MRD negativity rate after course 1 [ Time Frame: Up to 6 weeks ]
    Will be estimated along with the exact 95% confidence interval.

  5. Incidence of toxicity [ Time Frame: 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.



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02458014


Contacts
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Contact: Elias Jabbour, MD 713-792-4764 ejabbour@mdanderson.org

Locations
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United States, Texas
M D Anderson Cancer Center Recruiting
Houston, Texas, United States, 77030
Contact: Elias Jabbour    713-792-4764      
Principal Investigator: Elias Jabbour         
Sponsors and Collaborators
M.D. Anderson Cancer Center
National Cancer Institute (NCI)
Investigators
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Principal Investigator: Elias Jabbour M.D. Anderson Cancer Center

Additional Information:
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Responsible Party: M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier: NCT02458014     History of Changes
Other Study ID Numbers: 2014-0844
NCI-2015-01547 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
2014-0844 ( Other Identifier: M D Anderson Cancer Center )
P30CA016672 ( U.S. NIH Grant/Contract )
First Posted: May 29, 2015    Key Record Dates
Last Update Posted: May 24, 2019
Last Verified: May 2019

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Leukemia
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Leukemia, Lymphoid
Neoplasm, Residual
Philadelphia Chromosome
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Translocation, Genetic
Chromosome Aberrations
Pathologic Processes
Neoplastic Processes
Antineoplastic Agents, Immunological
Blinatumomab
Antibodies
Immunoglobulins
Antibodies, Monoclonal
Antibodies, Bispecific
Muromonab-CD3
Visilizumab
Immunologic Factors
Physiological Effects of Drugs
Antineoplastic Agents
Immunosuppressive Agents