Neoplasms

Symptoms and General Pathology

All Conditions

Musculoskeletal Diseases

Mouth and Tooth Diseases

Neoplasm Metastasis

Osteonecrosis

Bone Diseases

Bisphosphonate-Associated Osteonecrosis of the Jaw

Neoplastic Processes

Necrosis

Jaw Diseases

Stomatognathic Diseases

Bone Density Conservation Agents

All Drugs and Chemicals

Diphosphonates

Patient with cancer involving the bone treated with osteoclast inhibitor (bisphosphonate) and has developed ONJ

Patient with cancer involving the bone treated with osteoclast inhibitor (bisphosphonate) and has NOT developed ONJ

Catherine Van Poznak, MD

This study seeks to identify risk factors associated with the development of a jaw condition seen in patients with cancer treated with certain medications.

The goal of this research is to build an index of risk for estimating an individual's risk of developing osteonecrosis of the jaw (ONJ). The bisphosphonates are an important supportive therapy in the care of patients with metastatic bone disease; they are able to prevent catastrophic events such as fracture and spinal cord compression. However, ONJ has been associated with the use of the bisphosphonates and ONJ carries significant morbidity. Presently, there are insufficient data to calculate the ONJ risk benefit ratio of bisphosphonate use. An ONJ risk assessment tool would improve both the oncologist's and the dental health professional the ability to anticipate and potentially mitigate oral toxicities from bisphosphonate therapy.

This protocol consists of a case (ONJ) control (no ONJ) study to identify factors associated with the risk of ONJ and to build an index predictive of an individual's risk of developing ONJ. The index of ONJ risk will be comprised of clinical, epidemiologic and genetic factors

paraffin embedded tissue block and/or WBC

Genetic Risk of Osteonecrosis of the Jaw (ONJ) in Patients With Metastatic Cancer

National Institute of Dental and Craniofacial Research (NIDCR)

Indiana University

M.D. Anderson Cancer Center

Memorial Sloan Kettering Cancer Center

University of Michigan

Priniciple Investigator

Heart and Blood Diseases

Blood and Lymph Conditions

Immune System Diseases

Rare Diseases

Multiple Myeloma

Neoplasms, Plasma Cell

Osteolysis

Neoplasms by Histologic Type

Hemostatic Disorders

Blood Coagulation Disorders

Vascular Diseases

Paraproteinemias

Blood Protein Disorders

Hematologic Diseases

Hemorrhagic Disorders

Lymphoproliferative Disorders

Immunoproliferative Disorders

Zoledronic Acid

treatment with zoledronic acid for 4 years

treatment with zoledronic acid withheld after two years

Zoledronic acid will be given to all participants for two years. Then patients will be randomized to A receive 2 more years of treatment or B stop treatment.

Zoledronic acid

Thomas LunD, MD Ph.D.

Main hypothesis: Patients who continue zoledronic acid after year 2 have longer time until progression in bone disease compared to patients who stop treatment after two years?

Secondary hypothesis: Serum will bone markers increase prior to progression in bone disease in the individual patient?

Secondary hypothesis: Low-dose CT will detect more cases of osteolytic bone disease in Multiple Myeloma compared to conventional radiography

Newly diagnosed myeloma patients will be followed for 4 years. The first two years they will be treated with zoledronic acid monthly. At year 2 they will be randomized to A continue treatment for 2 more years or B stop treatment. The primary outcome of the study will be time to progressive bone disease from year 2 and onward.

Serum bone markers will be measured throughout the study. In patients who experience progressive bone disease, development of bone markers prior to the radiological progression will be investigated to see the if it could have been predicted with the use of serum markers

During the four year period patients will have low-dose CT superior and conventional radiography made at predefined time points. The secondary outcome of the study is to compare the sensitivity of the two modalities

Prolonged Protection From Bone Disease in Multiple Myeloma

Magnolia Study Prolonged Protection From Bone Disease in Multiple Myeloma. An Open Label Phase 3 Multicenter International Randomised Trial

Patients will have low-dose CT and conventional x-ray made at predefined time points to compare the sensitivity between the two modalities

After two years of zoledronic acid treatment patients will be randomized to A continue treatment B stop treatment.

Development in bone markers prior to progression in osteolytic lesions will be investigated

Thomas Lund

MD Ph.D.

Nutritional and Metabolic Diseases

Leukemia

Precursor Cell Lymphoblastic Leukemia-Lymphoma

Leukemia, Lymphoid

Osteoporosis

Lymphoma

Lymphatic Diseases

Bone Diseases, Metabolic

Metabolic Diseases

Acute Lymphoblastic Leukemia

Lymphoblastic Lymphoma

Acute Graft Versus Host Disease

Lymphosarcoma

Intravenous Zoledronic Acid 0.025mg/kg at baseline and 6 months

This study explores the effect of zoledronic acid on incident vertebral fractures and osteonecrotic lesions in children recently diagnosed with acute lymphoblastic leukemia.

Intravenous Zoledronic Acid for the Treatment of Osteoporosis and Osteonecrosis in Children With Leukemia: A Pilot Study

To assess the effect of zoledronic acid on preventing incident vertebral fractures as measured by lateral spine radiographs at 15 months post-diagnosis compared to baseline (with baseline occurring 3 months post-diagnosis). An incident vertebral fracture on lateral spine radiographs will be defined as a new fracture (Genant Grade 1 or more) in a previously normal vertebral body, or worsening of an existing fracture (increase in Genant Grade by at least 1) on the follow-up x-ray that takes place 12 months after the first dose.

Children's Hospital of Eastern Ontario

Wounds and Injuries

Behaviors and Mental Disorders

Head and Neck Neoplasms

Osteoradionecrosis

Radiation Injuries

Quality of Life

Antibodies

Antibodies, Monoclonal

Immunoglobulins

Araceli Diez-Fraile, PhD

Johan Abeloos, MD

The investigators aim to develop a prospective database in which patient demographics, surgical, dental, prosthetic and QOL parameters collected during consecutive visits within the framework of routine practice, are being registered for each oncological patient eligible for (immediate/delayed) fixed prosthodontic rehabilitation at time of oral cavity reconstruction

The number of patients requiring major ablative surgery in the oral cavity, including partial/radical mandibular or maxillary resection, due to a head and neck carcinoma, osteoradionecrosis (ORN), or medication-related osteonecrosis of the jaw (MRONJ) has not been accurately reported. Surgical reconstruction to restore oral function and aesthetics forms a challenge to maxillofacial surgeons, and greatly impacts patient' quality of life (QOL). Recently, an active collaboration between the surgeons of the Oral and Maxillofacial Surgery Unit and the prosthodontist (LB) of the Department of Dentistry at the General Hospital Saint-John Bruges led to the development of the "Oncology-bridge (O-bridge)" protocol, which offers (immediate/delayed) fixed prosthetic rehabilitation in a minimum of sessions and a strongly reduced two-week treatment time, consequently accelerating patient' improved QOL at a considerably reduced cost.

The investigators aim to develop a prospective database in which patient demographics, surgical, dental, prosthetic and QOL parameters collected during consecutive visits within the framework of routine practice, are being registered for each oncological patient eligible for (immediate/delayed) fixed prosthodontic rehabilitation at time of oral cavity reconstruction This could provide the investigators with more information about potential patient, surgical and prosthetic factors influencing short- and long-term biological and mechanical stability, as well as patient QOL. Moreover, registration of those results could function as a measurement of quality of care, and could be used for sample size calculation for future large prospective trials.

Prospective Registry of Prosthodontic Rehabilitation in Oncology Patients Undergoing Jaw Reconstruction

AZ Sint-Jan AV

Maxillofacial surgeon, Head of Department

Hypertension

Antihypertensive Agents

Patients will begin Intensive antihypertensive therapy to achieve the targeted blood pressure (targeted to the 50-75th percentile for age, sex, and height) on day 4 of Remission Induction on TOT17 and continue during steroid containing phases until the completion of reinduction II.

Patients will begin Conventional antihypertensive therapy to achieve the targeted blood pressure (targeted to the 90-95th percentile for age, sex, and height) on day 4 of Remission Induction on TOT17 and continue during steroid containing phases until the completion of reinduction II.

Receives intensive antihypertensive therapy

Intensive Antihypertensive Therapy

Receives conventional antihypertensive therapy

Conventional Antihypertensive Therapy

The symptom survey is comprised of the PROMIS Ped 25 profile, PROMIS pain interference 8a, PROMIS physical activity 8a, and PROMIS mobility 8a during induction (day 23-28), during week 17 of continuation (+/- 2 weeks), and continuation week 49 (+/- 3 weeks).

Symptom Survey

Patients will be interviewed by a trained examiner about their treatment and symptom burden on Week 49 of TOT17 Continuation Therapy. The interview will be recorded and will take about 30-45 minutes.

Semi-structured interview

Seth E. Karol, MD

This is a randomized unblinded Phase II clinical trial evaluating the impact of intensive antihypertensive control (targeted to the 50-75th percentile for age, sex, and height) compared to conventional antihypertensive control (targeted to the 90-95th percentile for age, sex, and height) on the incidence of radiographically extensive osteonecrosis in children and young adults receiving treatment for newly diagnosed acute lymphoblastic leukemia/lymphoma (ALL).

Primary Objective

* Compare the frequency of radiographically extensive osteonecrosis in patients receiving intensive compared to conventional antihypertensive therapy.

Secondary Objectives

* Evaluate the efficacy of intensive antihypertensive control compared to conventional antihypertensive control in the prevention of clinically significant (CTCAE Grade 2 or higher) and radiologically extensive osteonecrosis, overall and stratified by joints.
* Compare the frequency of clinically significant and radiographically extensive osteonecrosis in patients receiving antihypertensive therapy and historical controls.
* Compare blood pressures achieved in intensive and conventional arms using both pressures obtained as part of routine patient care and ambulatory blood pressure monitoring.
* Compare levels of vascular dysfunction as measured physiologically, radiographically, and in blood samples in patients receiving intensive compared to standard antihypertensive therapy.

Exploratory Objectives

* Identify predictive patterns of blood biomarkers which identify patients at high- risk of developing clinically significant osteonecrosis.
* Identify MRI findings during late induction which correlate with osteonecrosis lesions seen during reinduction.
* Identify patterns of diurnal blood pressure variation as measured by ambulatory blood pressure monitoring associated with the later development of osteonecrosis.
* Compare induction blood pressure control and intervention arm to echocardiographic changes at reinduction II.
* Evaluate patient-reported, health-related quality of life in patients during induction and after 1.5 years of therapy when many experience the symptoms of osteonecrosis.

Patient randomization will be stratified based on patient's location (Memphis vs. other), use of antihypertensives prior to randomization, and factors known to influence osteonecrosis risk, specifically sex and self-declared race (non-Hispanic white vs. other). A target systolic blood pressure range will be chosen for each participant based on their randomization arm, age, sex, and height.

Patients will be randomized on day 4 of induction therapy to either conventional or intensive blood pressure goals. Patients will be treated with antihypertensive therapy to achieve blood pressure control as indicated by their randomized arm. Therapy will be adjusted every 3-4 days as needed to achieve targeted control based on the mean of blood pressures obtained in that period. Treatment of hypertension to the target will continue until the completion of reinduction II therapy. Patients will be evaluated for osteonecrosis as indicated in their primary therapeutic protocol using MRI during reinduction II.

Patients will be asked to complete a symptom survey and a semi-structured interview.

Evaluation of the MRIs defining the primary endpoint will be performed by a blinded radiologist.

Hypertension Intervention to Reduce Osteonecrosis in Children With Acute Lymphoblastic Leukemia/Lymphoma

Individual participant de-identified datasets containing the variables analyzed in the published article will be made available (related to the study primary or secondary objectives contained in the publication). Supporting documents such as the protocol, statistical analyses plan, and informed consent are available through the CTG website for the specific study. Data used to generate the published article will be made available at the time of article publication. Investigators who seek access to individual level de-identified data will contact the computing team in the Department of Biostatistics (ClinTrialDataRequest@stjude.org) who will respond to the data request.

Involvement of \>=30% of the epiphyseal surface of either the hip or knee by prospective MRI during reinduction II

CTCAE grade 2 or high osteonecrosis vs. Total 16 matched controls

Comparison of repeated systolic and diastolic blood pressure measures between randomized treatment arms

Comparison between randomized treatment arms

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Genetic Risk of Osteonecrosis of the Jaw (ONJ) in Patients With Metastatic Cancer	NCT01325142	Bone Diseases Metastases Osteonecrosis Bisphosphonate-...		21 Years -	University of Michigan
Prolonged Protection From Bone Disease in Multiple Myeloma	NCT02286830	Multiple Myelom...	Zoledronic acid	18 Years -	Odense University Hospital
Intravenous Zoledronic Acid for the Treatment of Osteoporosis and Osteonecrosis in Children With Leukemia: A Pilot Study	NCT02632903	Osteoporosis Osteonecrosis Acute Lymphobla...	Zoledronic acid	8 Years - 16 Years	Children's Hospital of Eastern Ontario
Intravenous Zoledronic Acid for the Treatment of Osteoporosis and Osteonecrosis in Children With Leukemia: A Pilot Study	NCT02632903	Osteoporosis Osteonecrosis Acute Lymphobla...	Zoledronic acid	8 Years - 16 Years	Children's Hospital of Eastern Ontario
Prospective Registry of Prosthodontic Rehabilitation in Oncology Patients Undergoing Jaw Reconstruction	NCT02661139	Head and Neck C... Osteonecrosis Osteoradionecro...		-	AZ Sint-Jan AV
Prospective Registry of Prosthodontic Rehabilitation in Oncology Patients Undergoing Jaw Reconstruction	NCT02661139	Head and Neck C... Osteonecrosis Osteoradionecro...		-	AZ Sint-Jan AV
Prolonged Protection From Bone Disease in Multiple Myeloma	NCT02286830	Multiple Myelom...	Zoledronic acid	18 Years -	Odense University Hospital
Genetic Risk of Osteonecrosis of the Jaw (ONJ) in Patients With Metastatic Cancer	NCT01325142	Bone Diseases Metastases Osteonecrosis Bisphosphonate-...		21 Years -	University of Michigan
Hypertension Intervention to Reduce Osteonecrosis in Children With Acute Lymphoblastic Leukemia/Lymphoma	NCT04401267	Hypertension Osteonecrosis Osteonecrosis D...	Intensive Antih... Conventional An... Symptom Survey Semi-structured...	10 Years -	St. Jude Children's Research Hospital
Hypertension Intervention to Reduce Osteonecrosis in Children With Acute Lymphoblastic Leukemia/Lymphoma	NCT04401267	Hypertension Osteonecrosis Osteonecrosis D...	Intensive Antih... Conventional An... Symptom Survey Semi-structured...	10 Years -	St. Jude Children's Research Hospital
Prolonged Protection From Bone Disease in Multiple Myeloma	NCT02286830	Multiple Myelom...	Zoledronic acid	18 Years -	Odense University Hospital

Spots Global Cancer Trial Database for osteonecrosis