Clinical trial NCT02598401: The British Osteonecrosis Study
Official title: The British Osteonecrosis Study: A Prospective Multi-centre Study to Examine the Natural History of Osteonecrosis in Older Children, Teenagers and Young Adults With Acute Lymphoblastic Leukaemia and Lymphoblastic Lymphoma
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Osteonecrosis
Lead sponsor: University of Leeds
Sponsor class: OTHER
First posted: 2015-11-05
Enrollment: 50
Sex: ALL
Minimum age (years): 10
Maximum age (years): 25
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Children, teenagers or young adults between the age of 10 (including the day of the 10th birthday)and 24 years 364 days (at the time of diagnosis) with a first diagnosis of acute lymphoblastic leukaemia or lymphoblastic lymphoma (T-NHL or SmIg negative precursor B-NHL) diagnosed under standard criteria are eligible for BONES.

Brief summary: The aim of this research is to examine the natural history of osteonecrosis in older children, teenagers and young adults with acute lymphoblastic leukaemia and lymphoblastic lymphoma within the UK. In addition to using and validating new, internationally agreed, standard definitions for osteonecrosis, this study will provide the data needed to develop a radiological classification which correlates with clinical status.

Detailed description: Children, teenagers or young adults between the age of 10 (including the day of the 10th birthday) and 24 years 364 days (at the time of diagnosis) with a first diagnosis of acute lymphoblastic leukaemia or lymphoblastic lymphoma (T-NHL or SmIg negative precursor B-NHL) diagnosed under standard criteria are eligible for BONES.

The recruitment target is 50 over a 2 year period, which is based on an anticipated ascertainment target of 75%.

Information will be collected on basic demographics, presenting features and diagnosis at initial recruitment. Further data will be collected at the end of induction to ascertain treatment and response, along with results of relevant investigations performed in induction detailed below. Clinical information collected will include height, weight and puberty stage. At the four subsequent time points when MRI imagine is performed further data will also be collected, including a physiotherapy assessment using a structured assessment tool and child health assessment questionnaire, and biochemical information.

Investigations

The results of the following investigations, usually performed as part of the routine assessment, will be collected:

1. At diagnosis - highest white cell count, immunophenotype, cytogenetics, molecular results; albumin; lipid profile; vitamin D level, PTH, bone profile
2. At the end of induction - MRD result, flow cytometry from end of induction bone marrow; albumin; lipid profile plus results of additional investigations of vitamin D, PTH and bone profile if performed.

DEXA scans should be performed on all children \>10y old and on treatment for ALL. It is recommended that a DEXA scan is performed at diagnosis and then annually. The results of these DEXA scans will be collected.

MRI of the hips, knees and ankles should comprise of unenhanced coronal T1 and STIR images as a minimum protocol. Knees and ankles can be imaged together. Where further information of a specific joint is needed pre-treatment additional sequences in different planes could be performed at the discretion of the participating centre. MRI will be performed at the following time points:

1. Within 4 weeks of diagnosis
2. At the end of delayed intensification
3. One year after the start of maintenance
4. Two years after the start of maintenance
5. Three years after the start of maintenance

In the event of the development of osteonecrosis the patient should be managed according to local protocols and at the discretion of their own consultant. Information on treatment will be collected.

Radiological review:

A central review panel consisting of Paediatric Radiologists with an interest in paediatric haematology will meet quarterly to review each MRI in order to agree the grade of osteonecrosis and noting specific features according to the study radiology proforma.

Eligibility criteria: Inclusion Criteria:

* first diagnosis of acute lymphoblastic leukaemia or lymphoblastic lymphoma (T-NHL or SmIg negative precursor B-NHL)

Exclusion Criteria:

- inability to have MRI scans of lower limbs

Primary outcomes:
measure: Incidence of osteonecrosis
timeFrame: 5 years
Secondary outcomes:
measure: Risk factors for development of osteonecrosis.
timeFrame: 5 years
measure: Radiological features for prediction of progression of osteonecrosis
timeFrame: 5 years
Other outcomes:
Locations:
city: Birmingham
country: United Kingdom
facility: Birmingham Children's Hospital
city: Leeds
country: United Kingdom
facility: Leeds Children's Hospital
city: Leeds
country: United Kingdom
facility: St James's University Hospital
city: Southampton
country: United Kingdom
facility: Southampton Children's Hospital
Study officials:
affiliation: University of Leeds
name: Nadia L Amin, MBChB
role: PRINCIPAL_INVESTIGATOR
References:
citation: Amin N, Kinsey S, Feltbower R, Kraft J, Whitehead E, Velangi M, James B. British OsteoNEcrosis Study (BONES) protocol: a prospective cohort study to examine the natural history of osteonecrosis in older children, teenagers and young adults with acute lymphoblastic leukaemia and lymphoblastic lymphoma. BMJ Open. 2019 May 22;9(5):e027204. doi: 10.1136/bmjopen-2018-027204.