Hypertension Intervention to Reduce Osteonecrosis in Children With Acute Lymphoblastic Leukemia/Lymphoma
3 other identifiers
interventional
51
1 country
2
Brief 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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P25-P50 for phase_2 hypertension
Started Oct 2020
Longer than P75 for phase_2 hypertension
2 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
May 13, 2020
CompletedFirst Posted
Study publicly available on registry
May 26, 2020
CompletedStudy Start
First participant enrolled
October 15, 2020
CompletedPrimary Completion
Last participant's last visit for primary outcome
September 25, 2023
CompletedResults Posted
Study results publicly available
July 11, 2024
CompletedStudy Completion
Last participant's last visit for all outcomes
October 7, 2025
CompletedNovember 3, 2025
October 1, 2025
2.9 years
May 13, 2020
June 14, 2024
October 29, 2025
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Extensive Radiographic Osteonecrosis
Involvement of \>=30% of the epiphyseal surface of either the hip or knee by prospective MRI during reinduction II
during reinduction II therapy, approximately 9 months into therapy.
Secondary Outcomes (13)
Rate of Clinically Significant Osteonecrosis
any time during leukemia therapy, approximately 2.5 years
Rate of Clinically Significant Osteonecrosis vs. Historical Control
any time during leukemia therapy, approximately 2.5 years
Blood Pressure Control on Trial
first 9 months of therapy
Biomarkers of Vascular Dysfunction - eNO Synthetase (pg/mL)
3 weeks and 9 months into therapy
Biomarker of Vascular Dysfunction - Von Willebrand Factor (%)
3 weeks and 9 months into therapy
- +8 more secondary outcomes
Study Arms (2)
Intensive Antihypertensive Therapy
EXPERIMENTALPatients 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.
Conventional Antihypertensive Therapy
ACTIVE COMPARATORPatients 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.
Interventions
Receives intensive antihypertensive therapy
Receives conventional antihypertensive therapy
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).
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.
Eligibility Criteria
You may qualify if:
- 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).
You may not qualify if:
- 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.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (2)
St. Jude Affiliate Clinic - Novant Health Hemby Children's Hospital
Charlotte, North Carolina, 28204, United States
St. Jude Children's Research Hospital
Memphis, Tennessee, 38105, United States
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Seth Karol, MD
- Organization
- St. Jude Children's Research Hospital
Study Officials
- PRINCIPAL INVESTIGATOR
Seth E. Karol, MD
St. Jude Children's Research Hospital
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- OTHER
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- RANDOMIZED
- Masking
- SINGLE
- Who Masked
- OUTCOMES ASSESSOR
- Masking Details
- Evaluation of the MRIs defining the primary endpoint will be performed by a blinded radiologist.
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
May 13, 2020
First Posted
May 26, 2020
Study Start
October 15, 2020
Primary Completion
September 25, 2023
Study Completion
October 7, 2025
Last Updated
November 3, 2025
Results First Posted
July 11, 2024
Record last verified: 2025-10
Data Sharing
- IPD Sharing
- Will share
- Shared Documents
- STUDY PROTOCOL, SAP, ICF
- Time Frame
- Data will be made available at the time of article publication.
- Access Criteria
- Data will be provided to researchers following a formal request with the following information: full name of requestor, affiliation, data set requested, and timing of when data is needed. As an informational point, the lead statistician and study principal investigator will be informed that primary results datasets have been requested.
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.