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

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.

Conditions

• Hypertension
• Osteonecrosis
• Osteonecrosis Due to Drug

Interventions

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.

Sponsors & Collaborators

• National Cancer Institute (NCI)

  collaborator NIH

• St. Jude Children's Research Hospital

  lead OTHER

Principal Investigators

• Seth E. Karol, MD · St. Jude Children's Research Hospital

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

SINGLE

Model

PARALLEL

Eligibility

Min Age

10 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2020-10-15

Primary Completion

2023-09-25

Completion

2025-10-07

FDA Drug

Yes

Countries

• United States

Study Locations