NCT04401267

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

• Status: Completed
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 51 (actual)
• Sponsor: St. Jude Children's Research Hospital · Academic / Other
• Sex: All
• Age: 10 Years
• Healthy volunteers: Not accepted

Summary

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.

Detailed description

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.

Conditions

• Hypertension
• Osteonecrosis
• Osteonecrosis Due to Drug

Interventions

Type	Name	Description
DRUG	Intensive Antihypertensive Therapy	Receives intensive antihypertensive therapy
DRUG	Conventional Antihypertensive Therapy	Receives conventional antihypertensive therapy
OTHER	Symptom Survey	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).
OTHER	Semi-structured interview	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.

Timeline

• Start date: 2020-10-15
• Primary completion: 2023-09-25
• Completion: 2025-10-07
• First posted: 2020-05-26
• Last updated: 2025-11-03
• Results posted: 2024-07-11

Locations

2 sites across 1 country: United States

Regulatory

• FDA-regulated drug study