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Does CMV Induced Changes in NK Lymphocyte Biology Influence the Effectiveness of Antibody Therapy Used to Treat B Cell Lymphoproliferative Diseases?

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ClinicalTrials.gov Identifier: NCT03417414
Recruitment Status : Not yet recruiting
First Posted : January 31, 2018
Last Update Posted : February 7, 2018
Sponsor:
Information provided by (Responsible Party):
Ottawa Hospital Research Institute

Brief Summary:
This is an observational cohort study of patients with a new diagnosis of B cell Chronic Lymphocytic Leukemia or B cell Non-Hodgkin's Lymphoma who will receive an anti-CD20 monoclonal antibody treatment during the induction phase of their treatment. Throughout the study, patients will have four blood draws at specified time points throughout the study. The initial blood draw will be analysed test patients for Cytomegalovirus and conduct a g-NK cell analysis. The final three blood draws will be conducted to analyse the g-NK cells at specified time points. The objectives of this study are to: 1) characterize the frequency of CMV (+) and g-NK (+) individuals in the B-NHL and B-CLL populations, 2) Determine changes in circulating g-NK cells during and after anti-CD20 monoclonal antibody containing remission induction chemotherapy and 3) Evaluate whether the presence of g-NK cells improve the outcome of anti-CD20 monoclonal antibody containing remission induction treatment of patients with B-NHL or B-CLL.

Condition or disease
B Cell Lymphocytic Leukemia B Cell Non-Hodgkin's Lymphoma

Detailed Description:

CMV infection results in a unique population of highly effective ADCC effector cells (g-NK) in more than 50% of individuals. Unlike most NK cells, g-NK cells are long-lived and persist for years following primary infection. The g-NK population enlarges following antibody binding through their Fc receptors (FcR) and target engagement by the antibody. The addition of rituximab and other monoclonal antibodies directed against B lymphocyte targets to remission-induction therapy has improved the depth and durability of response for patients with B cell lymphoproliferative diseases, such as Non-hodgkin's lymphoma (NHL) and chronic lymphocytic leukemia (CLL). The effects of rituximab and other monoclonal anti-cancer antibodies are at least partially mediated through ADCC mechanisms.

The purpose of this study is to examine the clinically relevant aspects of g-NK biology during antibody-containing therapy of lymphoproliferative diseases including whether the presence of g-NK might correlate with improved treatment responses.

Up to 160 patients with either B cell NHL or CLL will be enrolled in this study.

The study enrollment will occur over approximately 2 years. Patients will only be involved in this study until their blood samples are collected at the time point described below.

The following data will be abstracted from the clinical record over the course of the study:

  • Age (at beginning of remission-induction therapy)
  • Gender
  • Weight and height
  • Pathological diagnosis including subtype and genetic testing when available.
  • Stage at diagnosis
  • Prognostic index score (IPI or FLIPI as appropriate)
  • Date that remission-induction therapy begins
  • Chemotherapy used for remission-induction.
  • Dose of anti-CD20 antibody administered during remission-induction
  • Remission status after 3 cycles of remission-induction therapy (if available)
  • Details of maintenance therapy (drug, dose, schedule)
  • Date of progression or relapse.

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Study Type : Observational
Estimated Enrollment : 160 participants
Observational Model: Cohort
Time Perspective: Prospective
Official Title: Does CMV Induced Changes in NK Lymphocyte Biology Influence the Effectiveness of Antibody Therapy Used to Treat B Cell Lymphoproliferative Diseases?
Estimated Study Start Date : March 1, 2018
Estimated Primary Completion Date : March 1, 2021
Estimated Study Completion Date : March 1, 2021

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Lymphoma

Group/Cohort
B-CLL
Patients with B-Cell CLL
B-NHL
Patients with B-Cell NHL



Primary Outcome Measures :
  1. Is the presence of gNK cells associated with better clinical responses in rituxan treated lymphoma patients? [ Time Frame: 2 years ]
    Blood samples will be collected at 4 specified time points from each participant.


Secondary Outcome Measures :
  1. Are circulating gNK cells capable of killing CD20+ lymphoma cells through rituximab mediated ADCC mechanisms. [ Time Frame: 2 years ]
    Blood samples will be collected at 4 specified time points from each participant.


Biospecimen Retention:   Samples Without DNA

The CMV status of individuals will be measured by serology in the laboratory of Dr. Lee.

The presence and function of g-NK cells will be identified and quantified following staining with appropriate fluorescent monoclonal antibody conjugates using flow cytometry of peripheral blood.

Samples from individuals will be examined to determine changes over time associated with remission-induction and maintenance anti-CD20 based treatment.



Information from the National Library of Medicine

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Ages Eligible for Study:   Child, Adult, Older Adult
Sexes Eligible for Study:   All
Sampling Method:   Non-Probability Sample
Study Population
Patients with a new diagnosis of CD20 expressing B-NHL or CLL who will receive an anti-CD20 monoclonal antibody treatment during the induction phase of treatment who have not previously been exposed to cytotoxic chemotherapy medications.
Criteria

Inclusion Criteria:

  • New diagnosis of CD20 expressing B-NHL or CLL

    o Up to 1/3rd of enrolled patients may have CLL. Enrollment of patients with CLL will be halted if this criterion is reached.

  • Will receive an anti-CD20 monoclonal antibody treatment (including rituximab, obinatuzumab) during the induction phase of treatment
  • Has not previously received cytotoxic chemotherapy medications
  • Able to provide informed consent

Exclusion Criteria:

  • Comorbidities or frailty that would limit estimated survival to <1 year.
  • Will not receive active anti-CD20 containing remission induction therapy.

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): NCT03417414


Contacts
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Contact: Harold Atkins, MD FRCPC 613-737-7700 ext 70341 hatkins@toh.ca

Sponsors and Collaborators
Ottawa Hospital Research Institute
Investigators
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Principal Investigator: Harold Atkins, MD FRCP C The Ottawa Hospital
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Responsible Party: Ottawa Hospital Research Institute
ClinicalTrials.gov Identifier: NCT03417414    
Other Study ID Numbers: GNK Cells in CLL and NHL
First Posted: January 31, 2018    Key Record Dates
Last Update Posted: February 7, 2018
Last Verified: February 2018
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
Additional relevant MeSH terms:
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Lymphoma, B-Cell
Leukemia, B-Cell
Leukemia, Lymphocytic, Chronic, B-Cell
Lymphoproliferative Disorders
Lymphoma, Non-Hodgkin
Lymphoma
Neoplasms by Histologic Type
Neoplasms
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Leukemia, Lymphoid
Leukemia