Hypertension Intervention to Reduce Osteonecrosis in Children With Acute Lymphoblastic Leukemia/Lymphoma
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 51
- 试验地点
- 3
- 主要终点
- Extensive Radiographic Osteonecrosis
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Single (Outcomes Assessor)
盲法说明
Evaluation of the MRIs defining the primary endpoint will be performed by a blinded radiologist.
入排标准
- 年龄范围
- 10 Years 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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 TOT
- •Patient has completed ≤ 4 days of protocol therapy (patients are eligible on Day 4 of TOT17 therapy).
排除标准
- •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.
研究组 & 干预措施
Intensive Antihypertensive Therapy
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.
干预措施: Intensive Antihypertensive Therapy (Drug)
Intensive Antihypertensive Therapy
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.
干预措施: Symptom Survey (Other)
Intensive Antihypertensive Therapy
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.
干预措施: Semi-structured interview (Other)
Conventional Antihypertensive Therapy
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.
干预措施: Conventional Antihypertensive Therapy (Drug)
Conventional Antihypertensive Therapy
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.
干预措施: Symptom Survey (Other)
Conventional Antihypertensive Therapy
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.
干预措施: Semi-structured interview (Other)
结局指标
主要结局
Extensive Radiographic Osteonecrosis
时间窗: 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
次要结局
- Biomarker of Vascular Dysfunction - D-dimer (µg/mL)(3 weeks and 9 months into therapy)
- Biomarker of Vascular Dysfunction - PAI-1 (AU/mL)(3 weeks and 9 months into therapy)
- Biomarker of Vascular Dysfunction - Arterial Elasticity (ml/mmHg)(3 weeks and 3 months into therapy)
- Biomarker of Vascular Dysfunction - Pulse Wave Velocity (m/Sec)(3 weeks and 3 months into therapy)
- Biomarker of Vascular Dysfunction - Von Willebrand Factor (%)(3 weeks and 9 months into therapy)
- Biomarker of Vascular Dysfunction - ICAM-1 (ng/mL)(3 weeks and 9 months into therapy)
- Biomarker of Vascular Dysfunction - E-selectin (ng/mL)(3 weeks and 9 months into therapy)
- Rate of Clinically Significant Osteonecrosis(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 - TNF-alpha (pg/mL)(3 weeks and 9 months into therapy)
- Magnetic Resonance Imaging (MRI) of Right and Left Hip and Knee(3 weeks and 9 months into therapy)
- Rate of Clinically Significant Osteonecrosis vs. Historical Control(any time during leukemia therapy, approximately 2.5 years)