Oxford Pre-cancerous Lymphoproliferative Disorders Study (OxPLoreD)

Oxford Pre-cancerous Lymphoproliferative Disorders: Analysis and Interception Study

OxPLoreD is an observational cohort study to identify clinical, genomic and immunological predictive markers of progression to malignant disease. Open to individuals diagnosed in the last 3 years with high count MBL, Binet Stage A CLL, Immunoglobulin G/A/M (IgG, IgA, IgM) MGUS, asymptomatic WM not requiring treatment and smouldering myeloma not requiring treatment.

Study Overview

• Status: Recruiting
• Conditions: Pre-cancerous Lymphoproliferative Disorders

Detailed Description

The purpose of the study is to monitor patients with early stage lymphoproliferative disorders not meeting criteria for treatment, including early stage Chronic Lymphocytic Leukaemia (CLL), Monoclonal B-cell Lymphocytosis (MBL), Monoclonal Gammopathy of Uncertain Significance (MGUS), asymptomatic Waldenstroms Macroglobulinaemia (WM) and Smouldering Myeloma (SM).

Each of these disorders has a pre-cancerous phase when abnormalities can be seen in the blood, however treatment may not be required. A minority of people with early stage lymphoproliferative disorders will go on to need treatment for blood or bone marrow cancer.

Currently the investigators do not have a reliable way to predict which of these individuals with these disorders are more likely to develop a blood or bone marrow cancer. By studying a large group of individuals over time we hope to discover more about what factors might predict progression.The investigators may be able to identify markers which identify individuals who are more or less likely to develop blood or bone marrow cancer. These markers might be particular symptoms, gene changes called mutations or levels of particular molecules or cells in the blood or bone marrow. In the longer term this may enable us to identify those people who would benefit from certain types of treatment or from receiving treatment at an earlier stage and also to confidently reassure those who will never progress.

Patients will be studied for up to 5 years with blood, bone marrow and saliva samples taken at key time-points to help answer these questions. In addition to looking for these markers we will also collect information about:

• What it is like to live with one of these conditions
• How many people with these conditions develop other significant medical conditions, such as serious infections, thrombosis (blood clots) or other types of cancer.

• Study Type: Observational
• Enrollment (Estimated): 1650

Contacts and Locations

• Study Contact: Name: Tim Coutts; Phone Number: 01865 617080; Email: octo-oxplored@oncology.ox.ac.uk

Study Locations

• United Kingdom
  • Bournemouth, United Kingdom
    • Recruiting
    • Royal Bournemouth Hospital
  • Dudley, United Kingdom
    • Recruiting
    • Russells Hall Hospital
  • Great Yarmouth, United Kingdom
    • Recruiting
    • James Paget Hospital
  • Leicester, United Kingdom
    • Recruiting
    • Leicester Royal Infirmary
  • Liverpool, United Kingdom
    • Recruiting
    • Clatterbridge Cancer Centre
  • London, United Kingdom
    • Recruiting
    • King's College Hospital
  • London, United Kingdom
    • Recruiting
    • St George's Hospital
  • London, United Kingdom
    • Recruiting
    • Epsom Hospital
  • Newcastle, United Kingdom
    • Recruiting
    • Northern Centre for Cancer Care
  • North Shields, United Kingdom
    • Recruiting
    • North Tyneside General Hospital
  • Nottingham, United Kingdom
    • Recruiting
    • Queens Medical Centre
  • Oxford, United Kingdom, OX3 7LE
    • Recruiting
    • Churchill Hospital, Oxford University Hospitals Trust
    • Contact: Anna Schuh
  • Plymouth, United Kingdom
    • Recruiting
    • Derriford Hospital
  • Poole, United Kingdom
    • Recruiting
    • Poole Hospital
  • South Shields, United Kingdom
    • Recruiting
    • South Tyneside District Hospital
  • Sunderland, United Kingdom
    • Recruiting
    • Sunderland Royal Hospital
  • Taunton, United Kingdom
    • Recruiting
    • Musgrove Park Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Probability Sample

Study Population

The study targets three groups of pre-cancerous lymphoproliferative disorders

Description

Inclusion Criteria:

1. Patients diagnosed within the previous three years with one of the following:

   1. High count monoclonal B-cell lymphocytosis (MBL) i.e. clonal B-cell population 0.5-4.9 109/L
   2. Rai Stage 0-2/ Binet Stage A or Stage B Chronic Lymphocytic Leukaemia not meeting the IWCLL criteria for treatment
   3. IgG or IgA Monoclonal Gammopathy of Uncertain Significance meeting one of the following criteria:

   i) IgA paraprotein >10g/L or

   ii) IgG paraprotein >15g/L or

   iii) IgA/IgG paraprotein below these cut-offs but kappa:lambda light chain ratio of

   • <0.1 to >3.0 (For OUH participants or sites with no pre-defined cut offs for high risk MGUS) or
   • within the cut off criteria of the local laboratory ranges for high risk MGUS

   iv) Patients not meeting the cut-offs defined in points i) to iii) but who are referred to secondary care e.g. due to general practitioner (GP) concern or for investigation of symptoms

   d. IgM Monoclonal Gammopathy of Uncertain Significance meeting one of the following criteria: i) IgM paraprotein >10g/L or

   ii) IgM paraprotein <10g/L and difference between the kappa and lambda light chains of >50mg/L

   iii) Patients not meeting the cut-offs defined in point i) and ii) but who are referred to secondary care e.g. due to GP concern or investigation of symptoms

   e) Asymptomatic smouldering Waldenstrom's Macroglobulinaemia not meeting the criteria for treatment f) Smouldering myeloma not meeting the criteria for treatment

2. Eastern Cooperative Oncology Group (ECOG) performance status of 0,1 or 2
3. Age 16 years and over
4. Sign written informed consent
5. The patient is willing and able to comply with the protocol for the duration of the study and scheduled follow-up visits and examinations

Exclusion Criteria:

1. Pregnant or breast-feeding women. Pregnant or breast-feeding women may be re-screened following delivery and/or cessation of breastfeeding, as appropriate
2. Previous chemotherapy or immunotherapy for any haematological cancers
3. Treatment with any other investigational agent, or participation in an interventional clinical trial within 28 days prior to enrolment.
4. Patients in cohort 2 or 3 on anticoagulation for a diagnosis of pulmonary embolus or deep vein thrombosis within the last 3 months or with a mechanical heart valve or any other condition causing a significant risk of thromboembolism. Participants who are anticoagulated for atrial fibrillation are eligible, but will be asked to interrupt anticoagulation 3 days prior to bone marrow examination
5. Other psychological, social or medical condition, physical examination finding or laboratory abnormality that the investigator considers would make the patient a poor study candidate or could interfere with protocol compliance or the interpretation of study results.
6. Any other malignancy that requires active surgical or chemotherapeutic Patients on long term hormone therapies (e.g. Tamoxifen) are permitted to enrol at the discretion of investigator, after considering the overall clinical context
7. Any significant concurrent medical resulting in life-expectancy (including but no limited to renal, Hepatic, haematological gastrointestinal, endocrine pulmonary neurological, cerebral or psychiatric disease
8. For cohort 3: Any contraindication for MRI- presence of any metallic foreign body, eGFR <30 and allergy to gadolinium contrast

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort
Cohort 1; Participants with Monoclonal B-Cell Lymphocytosis or Asymptomatic Chronic Lymphocytic Leukaemia
Cohort 2; Participants with IgM Monoclonal Gammopathy or Asymptomatic Waldenstrom's Macroglobulinaemia
Cohort 3; Participants with IgA or IgG Monoclonal Gammopathy or Smouldering Myeloma

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The identification of predictive markers of progression to malignant disease	Relevant markers will be identified from the analysis of the clinical data in combination with the genomic and immunological data from the samples collected. The markers will be combined to produce a single probability risk score. The choice of relevant markers will be guided by emerging evidence and techniques under the guidance of the study scientific advisory board.	Duration of the study (5 years)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Patient reported outcome measures (PROM) via approved quality of life questionnaires.	Analysis of approved questionnaires: EORTC CLL17	Duration of study (5 years)
To study other clinically significant events, not inevitably due to disease progression in this patient cohort	Assessed by analysing suspected unexpected serious adverse reactions (SUSARs) reported	Duration of study (5 years)
Production of evidence-based standard of care guidelines for the monitoring and follow-up of patients with these pre-cancerous conditions	The identification of relevant markers can be used to create guidelines for optimal monitoring of patients with these pre-cancerous conditions	Duration of study (5 years)
Patient reported outcome measures (PROM) via approved quality of life questionnaires.	Analysis of approved questionnaires: EORTC NHL-LG20	Duration of study (5 years)
Patient reported outcome measures (PROM) via approved quality of life questionnaires.	Analysis of approved questionnaires: EORTC QLQ-C30	Duration of study (5 years)
Patient reported outcome measures (PROM) via approved quality of life questionnaires.	Analysis of approved questionnaires: EORTC QLQ-MY20	Duration of study (5 years)

Collaborators and Investigators

• Sponsor: University of Oxford
• Collaborators: Janssen Research & Development, LLC
• Investigators: Principal Investigator: Anna Schuh, University of Oxford

Study record dates

Study Major Dates

• Study Start (Actual): July 3, 2019
• Primary Completion (Estimated): July 1, 2024
• Study Completion (Estimated): July 1, 2026

Study Registration Dates

• First Submitted: June 25, 2019
• First Submitted That Met QC Criteria: July 16, 2019
• First Posted (Actual): July 17, 2019

Study Record Updates

• Last Update Posted (Actual): November 2, 2023
• Last Update Submitted That Met QC Criteria: November 1, 2023
• Last Verified: May 1, 2023

More Information

Terms related to this study

• Keywords: Lymphoproliferative Disorders; Monoclonal B-Cell Lymphocytosis; Asymptomatic Chronic Lymphocytic Leukaemia; IgM Monoclonal Gammopathy; Asymptomatic Waldenstrom's Macroglobulinaemia; Immunoglobulin A or G Monoclonal Gammopathy; Smouldering Myeloma; Pre-cancerous
• Additional Relevant MeSH Terms: Immune System Diseases; Lymphatic Diseases; Immunoproliferative Disorders; Lymphoproliferative Disorders
• Other Study ID Numbers: OCTO_091

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No