Phase 2
N=51
Hypertension Intervention to Reduce Osteonecrosis in Children With Acute Lymphoblastic Leukemia/Lymphoma
Hypertension · Osteonecrosis · Osteonecrosis Due to Drug
Bottom Line
View on ClinicalTrials.gov: NCT04401267 ↗Enrolled (actual)
51
Serious AEs
88.0%
Results posted
Jul 2024
Primary outcome: Primary: Extensive Radiographic Osteonecrosis — 20; 21; 1; 2 Participants — p=0.7139
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 2
- Interventions
- Intensive Antihypertensive Therapy (Drug); Conventional Antihypertensive Therapy (Drug); Symptom Survey (Other); Semi-structured interview (Other)
- Age
- Pediatric, Adult, Older Adult · 10+ yrs
- Sex
- All
- Sponsor
- St. Jude Children's Research Hospital
- Primary completion
- Sep 2023
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Extensive Radiographic Osteonecrosis |
20; 21; 1; 2 | 0.7139 |
| SECONDARY Rate of Clinically Significant Osteonecrosis |
— | — |
| SECONDARY Rate of Clinically Significant Osteonecrosis vs. Historical Control |
— | — |
| SECONDARY Blood Pressure Control on Trial |
114.00; 117.00; 70.00; 74.00 | — |
| SECONDARY Biomarkers of Vascular Dysfunction - eNO Synthetase (pg/mL) |
187.78; 267.03; 193.28; 266.53 | — |
| SECONDARY Biomarker of Vascular Dysfunction - Von Willebrand Factor (%) |
195.00; 191.00; 211.00; 164.00 | — |
| SECONDARY Biomarker of Vascular Dysfunction - TNF-alpha (pg/mL) |
0.87; 0.79; 1.56; 1.44 | — |
| SECONDARY Biomarker of Vascular Dysfunction - D-dimer (µg/mL) |
0.85; 0.60; 0.44; 0.29 | — |
| SECONDARY Biomarker of Vascular Dysfunction - PAI-1 (AU/mL) |
17.85; 15.80; 38.00; 41.10 | — |
| SECONDARY Biomarker of Vascular Dysfunction - E-selectin (ng/mL) |
23.53; 23.24; 65.16; 53.68 | — |
| SECONDARY Biomarker of Vascular Dysfunction - ICAM-1 (ng/mL) |
328.79; 314.22; 629.13; 639.25 | — |
| SECONDARY Biomarker of Vascular Dysfunction - Arterial Elasticity (ml/mmHg) |
11.60; 10.70; 12.30; 10.40 | — |
| SECONDARY Biomarker of Vascular Dysfunction - Pulse Wave Velocity (m/Sec) |
5.00; 5.35; 5.00; 5.30 | — |
| SECONDARY Magnetic Resonance Imaging (MRI) of Right and Left Hip and Knee |
1; 2; 1; 2; 1; 1 | — |
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.
Eligibility Criteria
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.
Data sourced from ClinicalTrials.gov (NCT04401267). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.