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

• Status: Recruiting
• Trial end date: 2025-03-01
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: St. Jude Children's Research Hospital
• Collaborator: National Cancer Institute (NCI)
• Treatments: Antihypertensive Agents; Lisinopril

Criteria

Inclusion Criteria:

• Patient is being treated for newly diagnosed acute lymphoblastic leukemia or lymphoma (ALL) on the TOT17 protocol. Patients do not need to be hypertensive to enroll.

• Patient is 10 years of age or older at the time of enrollment on TOT17.

• Patient has completed ≤ 4 days of protocol therapy (patients are eligible on Day 4 of TOT17 therapy).

Exclusion Criteria:

• Moderate-severe renal dysfunction (glomerular filtration rate <45 ml/min/1.73m2).

• Down's syndrome (germline Trisomy 21) or other syndrome resulting in growth delay or alterations in stature.

• Chronic inability to ambulate. Patients with limitations in movement due to acute complications of leukemia/lymphoma are not excluded.

• Permanent contraindication to MRI evaluation.

• Participants who are pregnant or lactating. Males or females of reproductive potential must agree to use effective contraception for the duration of study participation.

• Inability or unwillingness of research participant or legal guardian/representative to give written informed consent.