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Longitudinal Assessment of Marrow and Blood in Patients With Glioblastoma (LAMB-G)

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ClinicalTrials.gov Identifier: NCT04657146
Recruitment Status : Not yet recruiting
First Posted : December 8, 2020
Last Update Posted : July 29, 2022
Sponsor:
Information provided by (Responsible Party):
Duke University

Brief Summary:
The main goal of this study is to provide foundational data to drive translational approaches for an entirely novel category of immunotherapy.

Condition or disease Intervention/treatment
Glioblastoma Other: Biorepository

Detailed Description:

The investigators' recent studies show that large numbers of T cells in patients and mice with intracranial tumors are sequestered in bone marrow. This phenomenon mysteriously confines a pool of functional, naïve T cells with anti-tumor capacity to a compartment where they are unable to access tumor, eliciting a mode of T cell dysfunction categorized as "ignorance." The investigators have uncovered that loss of the sphingosine-1-phosphate receptor 1 (S1P1) from the surface of T cells mediates their sequestration in bone marrow, while blocking internalization of S1P1 facilitates stabilization of the receptor on T cells and frees them for anti-tumor activities. As the investigators look to design interventions targeting β-arrestin mediated S1P1 internalization as a novel anti-tumor strategy, they need to better understand variations in sequestration across patients, over time, and with treatment. Assessing these variations and biomarkers that may accompany them will help to establish a target treatment population, as well as the optimal timing for intervention.

Primary Objectives:

  1. Assess variations in blood and bone marrow T cell counts as they relate to treatment time-points in patients with glioblastoma (GBM).
  2. Assess variations in S1P1 levels and their correlation with blood and bone marrow T cell counts over the course of treatment in patients with GBM

Exploratory Objectives:

  1. Assess the associations between tumor size and degree of lymphopenia and bone marrow T cell sequestration observed.
  2. Compare The Cancer Genome Atlas (TCGA) subclasses with respect to the degree of lymphopenia and bone marrow T cell sequestration observed at diagnosis.
  3. Examine patient plasma, tumor supernatant, and tumor ribonucleic acid (RNA) for markers that are associated with lymphopenia, T cell S1P1 levels, and bone marrow T cell sequestration. Initial candidates will include transforming growth factor-β (TGFβ) 1/2, tumor necrosis factor (TNF), interleukin (IL)-33, IL-6, catecholamines, signal transducer and activator of transcription 3 (STAT3) RNA, and Kruppel-like factor 2 (KLF2) RNA.
  4. Compare T cell phenotypes in the blood and bone marrow of patients exhibiting versus not exhibiting T cell lymphopenia or sequestration.
  5. Compare differences in tumor-infiltrating lymphocyte numbers and phenotypes between patients with and without lymphopenia / sequestration at diagnosis.
  6. Establish baseline β-arrestin 1 and 2 expression in patients and assess variation across individuals.
  7. Archive samples for subsequent assessment of β-arrestin recruitment to the cytoplasmic component of T cell S1P1, as well as the capacity to inhibit such recruitment in vitro with candidate small molecules.

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Study Type : Observational
Estimated Enrollment : 40 participants
Observational Model: Case-Only
Time Perspective: Prospective
Official Title: Longitudinal Assessment of Marrow and Blood in Patients With Glioblastoma
Estimated Study Start Date : September 1, 2022
Estimated Primary Completion Date : November 1, 2023
Estimated Study Completion Date : November 1, 2024

Resource links provided by the National Library of Medicine


Group/Cohort Intervention/treatment
Patients with suspected newly-diagnosed Glioblastoma (GBM)
Patients, ≥18 years of age, with newly diagnosed GBM, World Health Organization (WHO) Grade IV, undergoing gross total resection (defined as >90% of contrast enhancing volume removed on post-operative MRI) and collection of blood, bone marrow, and tumor.
Other: Biorepository

Tumor collection (> 1cm3): Intraoperatively

Peripheral blood collection:

  • Intraoperatively (60mL)
  • Post-resection (30mL)
  • Post- standard of care treatment (30mL)

Bone marrow aspiration:

  • Intraoperatively (10mL)
  • Post-resection (5mL)
  • Post- standard of care treatment (5mL)




Primary Outcome Measures :
  1. Variations in blood and bone marrow T cell counts [ Time Frame: 2 years ]
    Assess variations in blood and bone marrow T cell counts as they relate to treatment time-points in patients with glioblastoma.

  2. Variations in Sphingosine-1-phosphate receptor 1 (S1P1) levels [ Time Frame: 2 years ]
    Assess variations in S1P1 levels and their correlation with blood and bone marrow T cell counts over the course of treatment in patients with glioblastoma.


Biospecimen Retention:   Samples With DNA
  1. Tumor collection
  2. Peripheral blood sample collection
  3. Bone marrow aspiration


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population
All patients meeting the terms of the inclusion and exclusion criteria above will be eligible to participate in the study. This includes all patients over 18 years of age, both sexes, and all minorities. A total of 40 patients will be enrolled in the study. Patients who are not confirmed to have GBM on histopathological analysis, or who do not qualify as gross total resection per the definition above will be removed from the study and replaced until a total of 40 patients is reached.
Criteria

Inclusion Criteria:

  • Age ≥18 years of age.
  • Suspected newly-diagnosed GBM, World Health Organization (WHO) Grade IV with intent for gross total resection (as defined above).
  • Accessibility for treatment and follow up.
  • Patient consent obtained according to Duke institutional policy.
  • Women of child bearing potential (WOCBP) must have a negative serum pregnancy test according to standard of care prior to surgery.

Exclusion Criteria:

  • Prior therapy (other than steroids or stereotactic biopsy) or concomitant immunotherapy.
  • Pregnant or breast-feeding during the study period.
  • Patients with an active infection, or febrile within 24 hours of surgery.
  • Patients with inflammatory bowel disease, systemic lupus erythematosus, rheumatoid arthritis, or other autoimmune disease.
  • Patients with history of or active hematologic or bone marrow diseases, including but not limited to diagnosed lymphomas, leukemias, sickle cell or other anemias not associated with their current condition or polycythemia vera.
  • Prior bone marrow harvests preceding this study.
  • Patients with known or suspected immunodeficiency or human immunodeficiency virus (HIV).
  • Hematocrit < 24 % pre-operatively.
  • Patients with a serious active infection or other serious underlying medical conditions that would impair the ability of the patient to receive protocol treatment or comply with protocol.

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): NCT04657146


Contacts
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Contact: Peter Fecci, M.D., Ph.D. 919 681 2610 peter.fecci@duke.edu
Contact: Claudia E Pamanes, M.P.H. 919 668 0897 claudia.pamanes@duke.edu

Locations
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United States, North Carolina
Duke University Medical Center
Durham, North Carolina, United States, 27710
Contact: Beth Perry, RN    919-681-2695    beth.perry@duke.edu   
Contact: Claudia E Pamanes, MPH    919-668-0897    claudia.pamanes@duke.edu   
Principal Investigator: Peter Fecci, M.D., Ph.D.         
Sponsors and Collaborators
Duke University
Investigators
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Principal Investigator: Peter Fecci, M.D., Ph.D. Duke University
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Responsible Party: Duke University
ClinicalTrials.gov Identifier: NCT04657146    
Other Study ID Numbers: Pro00107040
First Posted: December 8, 2020    Key Record Dates
Last Update Posted: July 29, 2022
Last Verified: March 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Duke University:
Glioblastoma, T cells, Sequestration
Sphingosine-1-phosphate receptor 1
β-arrestin, Bone marrow, Immunotherapy
Additional relevant MeSH terms:
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Glioblastoma
Astrocytoma
Glioma
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue