This phase II trial compares the effect of intensive (for example higher dose) therapy with medications used to treat high blood pressure versus standard therapy using lower dose of blood pressure medications for the reduction of osteonecrosis in children with acute lymphoblastic leukemia or lymphoma. High blood pressure (hypertension) can lead to a long-term complication called “osteonecrosis”. Osteonecrosis is a condition in which there is a loss of blood flow to bone tissue, which causes the bone to die. It is most common in the hips, knees, shoulders, and ankles. This study may help researchers find out if treating patients with intensive therapy is the same, better, or worse than treating patients with standard therapy.
Study sponsor and potential other locations can be found on ClinicalTrials.gov for NCT04401267.
PRIMARY OBJECTIVE:
I. Compare the frequency of radiographically extensive osteonecrosis in patients receiving intensive compared to conventional antihypertensive therapy.
SECONDARY OBJECTIVES:
I. Evaluate the efficacy of intensive antihypertensive control compared to conventional antihypertensive control in the prevention of clinically significant (Common Terminology Criteria for Adverse Events [CTCAE] grade 2 or higher) and radiologically extensive osteonecrosis, overall and stratified by joints.
II. Compare the frequency of clinically significant and radiographically extensive osteonecrosis in patients receiving antihypertensive therapy and historical controls.
III. Compare blood pressures achieved in intensive and conventional arms using both pressures obtained as part of routine patient care and ambulatory blood pressure monitoring.
IV. Compare levels of vascular dysfunction as measured physiologically, radiographically, and in blood samples in patients receiving intensive compared to standard antihypertensive therapy.
EXPLORATORY OBJECTIVES:
I. Identify predictive patterns of blood biomarkers which identify patients at high-risk of developing clinically significant osteonecrosis.
II. Identify magnetic resonance imaging (MRI) findings during late induction which correlate with osteonecrosis lesions seen during reinduction.
III. Identify patterns of diurnal blood pressure variation as measured by ambulatory blood pressure monitoring associated with the later development of osteonecrosis.
IV. Compare induction blood pressure control and intervention arm to echocardiographic changes at reinduction II.
V. 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.
OUTLINE: Patients are randomized to 1 of 2 arms.
ARM A (STANDARD): Patients receive anti-hypertensive therapy beginning on day 4 to keep blood pressure within the 90-95th percentile for age, sex, and height in the absence of disease progression or unacceptable toxicity. Patients also complete surveys over 20-30 minutes once on day 23-28 then on week 17 and 49. Patients may participate in an interview about their treatment and symptom burden over 30-45 minutes on week 49.
ARM B (INTENSIVE): Patients receive anti-hypertensive therapy beginning on day 4 to keep blood pressure within the 50-75th percentile for age, sex, and height in the absence of disease progression or unacceptable toxicity. Patients also complete surveys over 20-30 minutes once on day 23-28 then on week 17 and 49. Patients may participate in an interview about their treatment and symptom burden over 30-45 minutes on week 49.
Lead OrganizationSaint Jude Children's Research Hospital
Principal InvestigatorSeth Evan Karol
