HypertensionPhase 2NCT04401267
Hypertension Intervention to Reduce Osteonecrosis in Children With Acute Lymphoblastic Leukemia/Lymphoma
A Phase 2 study testing Intensive Antihypertensive Therapy, Conventional Antihypertensive Therapy and Symptom Survey in people with Hypertension and Osteonecrosis, run by St. Jude Children's Research Hospital at 2 sites in United States.
Trial 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… Read more about this study
- Who is it for?
- Ages 10 years and older
- Conditions the study is for
- Hypertension, Osteonecrosis, Osteonecrosis Due to Drug
- What is being tested?
- Intensive Antihypertensive Therapy, Conventional Antihypertensive Therapy and Symptom Survey
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 51 participants
- Where
- 2 sitesUnited States
- Study dates
- 15 Oct 2020to 7 Oct 2025
- Phase
- Phase 2
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 10 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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).
Who cannot join
- 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.
Trial locations and contacts
2 sites in 1 country.
United States2 sites
St. Jude Affiliate Clinic - Novant Health Hemby Children's Hospital
Charlotte, North Carolina, 28204
St. Jude Children's Research Hospital
Memphis, Tennessee, 38105
About this study
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
Read more
- 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.
Read the 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
- Being tested
- Intensive Antihypertensive Therapy, Conventional Antihypertensive Therapy, Symptom Survey, Semi-structured interview
- Keywords
- Acute Lymphoblastic Leukemia, Children, Hypertension, Osteonecrosis, Osteonecrosis Due to Drug
- Medical subject headings
- Hypertension, Osteonecrosis, Precursor Cell Lymphoblastic Leukemia-Lymphoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Intensive Antihypertensive TherapyDrug
Also called Hypotensive Therapy
Receives intensive antihypertensive therapy
Conventional Antihypertensive TherapyDrug
Also called Hypotensive Therapy
Receives conventional antihypertensive therapy
Symptom SurveyOther
Also called 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).
Semi-structured interviewOther
Also called 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.
| Study group | Role | What they receive |
|---|---|---|
| Intensive Antihypertensive Therapy | Experimental | 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. Receives: Drug: Intensive Antihypertensive Therapy; Other: Symptom Survey; Other: Semi-structured interview |
| Conventional Antihypertensive Therapy | Active comparator | 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: Drug: Conventional Antihypertensive Therapy; Other: Symptom Survey; Other: Semi-structured interview |
What is being measured
The primary outcome is the main question the study is designed to answer.
Extensive Radiographic Osteonecrosis
Involvement of >=30% of the epiphyseal surface of either the hip or knee by prospective MRI during reinduction II
Measured: during reinduction II therapy, approximately 9 months into therapy.
Secondary outcomes (13)
Rate of Clinically Significant Osteonecrosis
CTCAE grade 2 or high osteonecrosis
Measured: any time during leukemia therapy, approximately 2.5 years
Rate of Clinically Significant Osteonecrosis vs. Historical Control
CTCAE grade 2 or high osteonecrosis vs. Total 16 (TOTVXI-NCT00549848) matched controls
Measured: any time during leukemia therapy, approximately 2.5 years
Blood Pressure Control on Trial
Comparison of repeated systolic and diastolic blood pressure measures between randomized treatment arms
Measured: first 9 months of therapy
Biomarkers of Vascular Dysfunction - eNO Synthetase (pg/mL)
Comparison between randomized treatment arms
Measured: 3 weeks and 9 months into therapy
Biomarker of Vascular Dysfunction - Von Willebrand Factor (%)
Comparison between randomized treatment arms
Measured: 3 weeks and 9 months into therapy
Biomarker of Vascular Dysfunction - TNF-alpha (pg/mL)
Comparison between randomized treatment arms
Measured: 3 weeks and 9 months into therapy
Biomarker of Vascular Dysfunction - D-dimer (µg/mL)
Comparison between randomized treatment arms
Measured: 3 weeks and 9 months into therapy
Biomarker of Vascular Dysfunction - PAI-1 (AU/mL)
Comparison between randomized treatment arms
Measured: 3 weeks and 9 months into therapy
Biomarker of Vascular Dysfunction - E-selectin (ng/mL)
Comparison between randomized treatment arms
Measured: 3 weeks and 9 months into therapy
Biomarker of Vascular Dysfunction - ICAM-1 (ng/mL)
Comparison between randomized treatment arms
Measured: 3 weeks and 9 months into therapy
Biomarker of Vascular Dysfunction - Arterial Elasticity (ml/mmHg)
Comparison between randomized treatment arms
Measured: 3 weeks and 3 months into therapy
Biomarker of Vascular Dysfunction - Pulse Wave Velocity (m/Sec)
Comparison between randomized treatment arms
Measured: 3 weeks and 3 months into therapy
Magnetic Resonance Imaging (MRI) of Right and Left Hip and Knee
Comparison between randomized treatment arms on proportions of MRI identified lesions >= 30%.
Measured: 3 weeks and 9 months into therapy
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 May 2020
- Study start15 Oct 2020
- Primary completion25 Sep 2023
- Study completion7 Oct 2025
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for HypertensionStudies of the same condition, open and under way.
- More trials run by St. Jude Children's Research HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 51 participants (actual)
Sponsor and investigators
- Lead sponsor
- St. Jude Children's Research Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Responsible party
- Sponsor
- Investigators
- Seth E. Karol, MD, Principal investigator, St. Jude Children's Research Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04401267
- Sponsor's protocol ID
- HYPERION
- Other IDs
- 1K08CA250418, NCI-2020-03603
- Status last verified
- Jul 2026
- First submitted
- 13 May 2020
- Last updated
- 20 Jul 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: 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.