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Completed

NCT Number: NCT04401267

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

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.

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Key information

Conditions

Hypertension Bone Diseases Cardiovascular Diseases Hematologic Diseases Hemic and Lymphatic Diseases Immune System Diseases Immunoproliferative Disorders Leukemia Leukemia, Lymphoid Lymphatic Diseases Lymphoproliferative Disorders Musculoskeletal Diseases Necrosis Neoplasms Neoplasms by Histologic Type Osteonecrosis Osteonecrosis Due to Drug Pathologic Processes Pathological Conditions, Signs and Symptoms Precursor Cell Lymphoblastic Leukemia-Lymphoma Vascular Diseases

Age range

10 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

St. Jude Affiliate Clinic - Novant Health Hemby Children's Hospital, Charlotte, North Carolina, United States

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About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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.

Treatment and study plan

Intensive Antihypertensive Therapy

Drug

Receives intensive antihypertensive therapy

Other names: Hypotensive Therapy

Conventional Antihypertensive Therapy

Drug

Receives conventional antihypertensive therapy

Other names: Hypotensive Therapy

Symptom Survey

Other

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 names: Survey

semi-structured interview

Other

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.

Other names: Interview

Primary outcomes

  1. Extensive Radiographic Osteonecrosis

    Time frame: during reinduction II therapy, approximately 9 months into therapy.

    Involvement of >=30% of the epiphyseal surface of either the hip or knee by prospective MRI during reinduction II

Secondary outcomes

  1. Rate of Clinically Significant Osteonecrosis

    Time frame: any time during leukemia therapy, approximately 2.5 years

    CTCAE grade 2 or high osteonecrosis

  2. Rate of Clinically Significant Osteonecrosis vs. Historical Control

    Time frame: any time during leukemia therapy, approximately 2.5 years

    CTCAE grade 2 or high osteonecrosis vs. Total 16 (TOTVXI-NCT00549848) matched controls

  3. Blood Pressure Control on Trial

    Time frame: first 9 months of therapy

    Comparison of repeated systolic and diastolic blood pressure measures between randomized treatment arms

  4. Biomarkers of Vascular Dysfunction - eNO Synthetase (pg/mL)

    Time frame: 3 weeks and 9 months into therapy

    Comparison between randomized treatment arms

  5. Biomarker of Vascular Dysfunction - Von Willebrand Factor (%)

    Time frame: 3 weeks and 9 months into therapy

    Comparison between randomized treatment arms

  6. Biomarker of Vascular Dysfunction - TNF-alpha (pg/mL)

    Time frame: 3 weeks and 9 months into therapy

    Comparison between randomized treatment arms

  7. Biomarker of Vascular Dysfunction - D-dimer (µg/mL)

    Time frame: 3 weeks and 9 months into therapy

    Comparison between randomized treatment arms

  8. Biomarker of Vascular Dysfunction - PAI-1 (AU/mL)

    Time frame: 3 weeks and 9 months into therapy

    Comparison between randomized treatment arms

  9. Biomarker of Vascular Dysfunction - E-selectin (ng/mL)

    Time frame: 3 weeks and 9 months into therapy

    Comparison between randomized treatment arms

  10. Biomarker of Vascular Dysfunction - ICAM-1 (ng/mL)

    Time frame: 3 weeks and 9 months into therapy

    Comparison between randomized treatment arms

  11. Biomarker of Vascular Dysfunction - Arterial Elasticity (ml/mmHg)

    Time frame: 3 weeks and 3 months into therapy

    Comparison between randomized treatment arms

  12. Biomarker of Vascular Dysfunction - Pulse Wave Velocity (m/Sec)

    Time frame: 3 weeks and 3 months into therapy

    Comparison between randomized treatment arms

  13. Magnetic Resonance Imaging (MRI) of Right and Left Hip and Knee

    Time frame: 3 weeks and 9 months into therapy

    Comparison between randomized treatment arms on proportions of MRI identified lesions >= 30%.

Sponsors and collaborators

Lead sponsor

St. Jude Children's Research Hospital

Other

Collaborators

  • National Cancer Institute (NCI)

Registry information

Important dates

Study start
2020
Primary completion
2023
Study completion
2025
First posted
May 26, 2020
Registry last updated
Jul 20, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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