Clinical trial NCT04023747: Oxford Pre-cancerous Lymphoproliferative Disorders Study
Official title: Oxford Pre-cancerous Lymphoproliferative Disorders: Analysis and Interception Study
Study type: OBSERVATIONAL
Overall status: ACTIVE_NOT_RECRUITING
Conditions: Pre-cancerous Lymphoproliferative Disorders
Keywords: 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
Lymphoproliferative Disorders
Lead sponsor: University of Oxford
Sponsor class: OTHER
Collaborators: name: Janssen Research & Development, LLC
First posted: 2019-07-17
Enrollment: 574
Sex: ALL
Minimum age (years): 16
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: The study targets three groups of pre-cancerous lymphoproliferative disorders

Brief summary: 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: The identification of predictive markers of progression to malignant disease
timeFrame: Duration of the study (5 years)
Secondary outcomes:
measure: Patient reported outcome measures (PROM) via approved quality of life questionnaires.
timeFrame: Duration of study (5 years)
measure: To study other clinically significant events, not inevitably due to disease progression in this patient cohort
timeFrame: Duration of study (5 years)
measure: Production of evidence-based standard of care guidelines for the monitoring and follow-up of patients with these pre-cancerous conditions
timeFrame: Duration of study (5 years)
measure: Patient reported outcome measures (PROM) via approved quality of life questionnaires.
timeFrame: Duration of study (5 years)
measure: Patient reported outcome measures (PROM) via approved quality of life questionnaires.
timeFrame: Duration of study (5 years)
measure: Patient reported outcome measures (PROM) via approved quality of life questionnaires.
timeFrame: Duration of study (5 years)
Other outcomes:
Locations:
city: Bournemouth
country: United Kingdom
facility: Royal Bournemouth Hospital
city: Dudley
country: United Kingdom
facility: Russells Hall Hospital
city: Great Yarmouth
country: United Kingdom
facility: James Paget Hospital
city: Leicester
country: United Kingdom
facility: Leicester Royal Infirmary
city: Liverpool
country: United Kingdom
facility: Clatterbridge Cancer Centre
city: London
country: United Kingdom
facility: Epsom Hospital
city: London
country: United Kingdom
facility: King's College Hospital
city: London
country: United Kingdom
facility: St George's Hospital
city: Newcastle
country: United Kingdom
facility: Northern Centre for Cancer Care
city: North Shields
country: United Kingdom
facility: North Tyneside General Hospital
city: Nottingham
country: United Kingdom
facility: Queens Medical Centre
city: Oxford
country: United Kingdom
facility: Churchill Hospital, Oxford University Hospitals Trust
city: Plymouth
country: United Kingdom
facility: Derriford Hospital
city: Poole
country: United Kingdom
facility: Poole Hospital
city: South Shields
country: United Kingdom
facility: South Tyneside District Hospital
city: Sunderland
country: United Kingdom
facility: Sunderland Royal Hospital
city: Taunton
country: United Kingdom
facility: Musgrove Park Hospital
Study officials:
affiliation: University of Oxford
name: Anna Schuh
role: PRINCIPAL_INVESTIGATOR
References: