Hypertension, Osteonecrosis, Osteonecrosis Due to Drug
Conditions
Keywords
Acute Lymphoblastic Leukemia, Children, Hypertension, Osteonecrosis, Osteonecrosis Due to Drug
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.
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.
Interventions
DRUGIntensive Antihypertensive Therapy
Receives intensive antihypertensive therapy
DRUGConventional Antihypertensive Therapy
Receives conventional antihypertensive therapy
OTHERSymptom 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).
OTHERSemi-structured 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.
Sponsors
St. Jude Children's Research Hospital
National Cancer Institute (NCI)
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Masking description
Evaluation of the MRIs defining the primary endpoint will be performed by a blinded radiologist.
Eligibility
Sex/Gender
ALL
Age
10 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Extensive Radiographic Osteonecrosis | 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
| Measure | Time frame | Description |
|---|---|---|
| Rate of Clinically Significant Osteonecrosis | any time during leukemia therapy, approximately 2.5 years | CTCAE grade 2 or high osteonecrosis |
| Rate of Clinically Significant Osteonecrosis vs. Historical Control | any time during leukemia therapy, approximately 2.5 years | CTCAE grade 2 or high osteonecrosis vs. Total 16 (TOTVXI-NCT00549848) matched controls |
| Blood Pressure Control on Trial | first 9 months of therapy | Comparison of repeated systolic and diastolic blood pressure measures between randomized treatment arms |
| Biomarkers of Vascular Dysfunction - eNO Synthetase (pg/mL) | 3 weeks and 9 months into therapy | Comparison between randomized treatment arms |
| Biomarker of Vascular Dysfunction - Von Willebrand Factor (%) | 3 weeks and 9 months into therapy | Comparison between randomized treatment arms |
| Biomarker of Vascular Dysfunction - TNF-alpha (pg/mL) | 3 weeks and 9 months into therapy | Comparison between randomized treatment arms |
| Biomarker of Vascular Dysfunction - D-dimer (µg/mL) | 3 weeks and 9 months into therapy | Comparison between randomized treatment arms |
| Biomarker of Vascular Dysfunction - PAI-1 (AU/mL) | 3 weeks and 9 months into therapy | Comparison between randomized treatment arms |
| Biomarker of Vascular Dysfunction - E-selectin (ng/mL) | 3 weeks and 9 months into therapy | Comparison between randomized treatment arms |
| Biomarker of Vascular Dysfunction - ICAM-1 (ng/mL) | 3 weeks and 9 months into therapy | Comparison between randomized treatment arms |
| Biomarker of Vascular Dysfunction - Arterial Elasticity (ml/mmHg) | 3 weeks and 3 months into therapy | Comparison between randomized treatment arms |
| Biomarker of Vascular Dysfunction - Pulse Wave Velocity (m/Sec) | 3 weeks and 3 months into therapy | Comparison between randomized treatment arms |
| Magnetic Resonance Imaging (MRI) of Right and Left Hip and Knee | 3 weeks and 9 months into therapy | Comparison between randomized treatment arms on proportions of MRI identified lesions \>= 30%. |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORSeth E. Karol, MD
St. Jude Children's Research Hospital
Participant flow
Recruitment details
A total of 51 patients were enrolled into the study from 15OCT2020 to 28DEC2022. Of those, one patient was found to be ineligible to the study. Therefore, only 50 eligible patients will be included in the analyses of the study.
Participants by arm
| Arm | Count |
|---|---|
| Conventional (Standard) 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. | 25 |
| 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. | 25 |
| Total | 50 |
Baseline characteristics
| Characteristic | Conventional (Standard) Antihypertensive Therapy | Intensive Antihypertensive Therapy | Total |
|---|---|---|---|
| Age, Continuous | 13.93 years | 14.01 years | 13.98 years |
| Race/Ethnicity, Customized Black | 7 Participants | 6 Participants | 13 Participants |
| Race/Ethnicity, Customized Missing | 1 Participants | 2 Participants | 3 Participants |
| Race/Ethnicity, Customized Other | 4 Participants | 1 Participants | 5 Participants |
| Race/Ethnicity, Customized White | 13 Participants | 16 Participants | 29 Participants |
| Sex: Female, Male Female | 9 Participants | 10 Participants | 19 Participants |
| Sex: Female, Male Male | 16 Participants | 15 Participants | 31 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 25 | 1 / 25 |
| other Total, other adverse events | 24 / 25 | 24 / 25 |
| serious Total, serious adverse events | 22 / 25 | 22 / 25 |
Outcome results
Primary
Extensive Radiographic Osteonecrosis
Involvement of \>=30% of the epiphyseal surface of either the hip or knee by prospective MRI during reinduction II
Time frame: during reinduction II therapy, approximately 9 months into therapy.
Population: There were 21 of the 25 patients in conventional group, and 23 of the 25 patients in Intensive group reached reinduction II and had the MRI measurement during reinduction II.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Conventional (Standard) Antihypertensive Therapy | Extensive Radiographic Osteonecrosis | >=30% | 1 Participants |
| Conventional (Standard) Antihypertensive Therapy | Extensive Radiographic Osteonecrosis | <30% | 20 Participants |
| Intensive Antihypertensive Therapy | Extensive Radiographic Osteonecrosis | >=30% | 2 Participants |
| Intensive Antihypertensive Therapy | Extensive Radiographic Osteonecrosis | <30% | 21 Participants |
p-value: 0.7139Fisher Exact
Secondary
Biomarker of Vascular Dysfunction - Arterial Elasticity (ml/mmHg)
Comparison between randomized treatment arms
Time frame: 3 weeks and 3 months into therapy
Population: Two patients on the Conventional Arm and Intensive Arm, Week3, did not have the required measurement. Seven patients on the Conventional Arm and 8 patients on the Intensive Arm, Month3, did not have the required measurement.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Conventional (Standard) Antihypertensive Therapy | Biomarker of Vascular Dysfunction - Arterial Elasticity (ml/mmHg) | Week3 | 11.60 ml/mmHg |
| Conventional (Standard) Antihypertensive Therapy | Biomarker of Vascular Dysfunction - Arterial Elasticity (ml/mmHg) | Month3 | 12.30 ml/mmHg |
| Intensive Antihypertensive Therapy | Biomarker of Vascular Dysfunction - Arterial Elasticity (ml/mmHg) | Week3 | 10.70 ml/mmHg |
| Intensive Antihypertensive Therapy | Biomarker of Vascular Dysfunction - Arterial Elasticity (ml/mmHg) | Month3 | 10.40 ml/mmHg |
Secondary
Biomarker of Vascular Dysfunction - D-dimer (µg/mL)
Comparison between randomized treatment arms
Time frame: 3 weeks and 9 months into therapy
Population: Nine patients on the Conventional Arm and 8 patients on the Intensive Arm, Week3, did not have the required measurement. Four patients on the Conventional Arm and 5 patients on the Intensive Arm, Month9, did not have the required measurement.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Conventional (Standard) Antihypertensive Therapy | Biomarker of Vascular Dysfunction - D-dimer (µg/mL) | Week3 | 0.85 µg/mL |
| Conventional (Standard) Antihypertensive Therapy | Biomarker of Vascular Dysfunction - D-dimer (µg/mL) | Month9 | 0.44 µg/mL |
| Intensive Antihypertensive Therapy | Biomarker of Vascular Dysfunction - D-dimer (µg/mL) | Week3 | 0.60 µg/mL |
| Intensive Antihypertensive Therapy | Biomarker of Vascular Dysfunction - D-dimer (µg/mL) | Month9 | 0.29 µg/mL |
Secondary
Biomarker of Vascular Dysfunction - E-selectin (ng/mL)
Comparison between randomized treatment arms
Time frame: 3 weeks and 9 months into therapy
Population: One patient on the Conventional Arm and 2 patients on the Intensive Arm, Week3, did not have the required measurement. Five patients on the Conventional Arm and the Intensive Arm, Month9, did not have the required measurement.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Conventional (Standard) Antihypertensive Therapy | Biomarker of Vascular Dysfunction - E-selectin (ng/mL) | Week3 | 23.53 ng/mL |
| Conventional (Standard) Antihypertensive Therapy | Biomarker of Vascular Dysfunction - E-selectin (ng/mL) | Month9 | 65.16 ng/mL |
| Intensive Antihypertensive Therapy | Biomarker of Vascular Dysfunction - E-selectin (ng/mL) | Week3 | 23.24 ng/mL |
| Intensive Antihypertensive Therapy | Biomarker of Vascular Dysfunction - E-selectin (ng/mL) | Month9 | 53.68 ng/mL |
Secondary
Biomarker of Vascular Dysfunction - ICAM-1 (ng/mL)
Comparison between randomized treatment arms
Time frame: 3 weeks and 9 months into therapy
Population: One patient on the Conventional Arm and 2 patients on the Intensive Arm, Week3, did not have the required measurement. Five patients on the Conventional Arm and the Intensive Arm, Month9, did not have the required measurement.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Conventional (Standard) Antihypertensive Therapy | Biomarker of Vascular Dysfunction - ICAM-1 (ng/mL) | Week3 | 328.79 ng/mL |
| Conventional (Standard) Antihypertensive Therapy | Biomarker of Vascular Dysfunction - ICAM-1 (ng/mL) | Month9 | 629.13 ng/mL |
| Intensive Antihypertensive Therapy | Biomarker of Vascular Dysfunction - ICAM-1 (ng/mL) | Week3 | 314.22 ng/mL |
| Intensive Antihypertensive Therapy | Biomarker of Vascular Dysfunction - ICAM-1 (ng/mL) | Month9 | 639.25 ng/mL |
Secondary
Biomarker of Vascular Dysfunction - PAI-1 (AU/mL)
Comparison between randomized treatment arms
Time frame: 3 weeks and 9 months into therapy
Population: Nine patients on the Conventional Arm and the Intensive Arm, Week3, did not have the required measurement. Four patients on the Conventional Arm and 7 patients on the Intensive Arm, Month9, did not have the required measurement.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Conventional (Standard) Antihypertensive Therapy | Biomarker of Vascular Dysfunction - PAI-1 (AU/mL) | Week3 | 17.85 AU/mL |
| Conventional (Standard) Antihypertensive Therapy | Biomarker of Vascular Dysfunction - PAI-1 (AU/mL) | Month9 | 38.00 AU/mL |
| Intensive Antihypertensive Therapy | Biomarker of Vascular Dysfunction - PAI-1 (AU/mL) | Week3 | 15.80 AU/mL |
| Intensive Antihypertensive Therapy | Biomarker of Vascular Dysfunction - PAI-1 (AU/mL) | Month9 | 41.10 AU/mL |
Secondary
Biomarker of Vascular Dysfunction - Pulse Wave Velocity (m/Sec)
Comparison between randomized treatment arms
Time frame: 3 weeks and 3 months into therapy
Population: Two patients on the Conventional Arm and 3 patients on the Intensive Arm, Week3, did not have the required measurement. Eight patients on the Conventional Arm and on the Intensive Arm, Month3, did not have the required measurement.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Conventional (Standard) Antihypertensive Therapy | Biomarker of Vascular Dysfunction - Pulse Wave Velocity (m/Sec) | Week3 | 5.00 m/sec |
| Conventional (Standard) Antihypertensive Therapy | Biomarker of Vascular Dysfunction - Pulse Wave Velocity (m/Sec) | Month3 | 5.00 m/sec |
| Intensive Antihypertensive Therapy | Biomarker of Vascular Dysfunction - Pulse Wave Velocity (m/Sec) | Week3 | 5.35 m/sec |
| Intensive Antihypertensive Therapy | Biomarker of Vascular Dysfunction - Pulse Wave Velocity (m/Sec) | Month3 | 5.30 m/sec |
Secondary
Biomarker of Vascular Dysfunction - TNF-alpha (pg/mL)
Comparison between randomized treatment arms
Time frame: 3 weeks and 9 months into therapy
Population: One patient on the Conventional Arm and 2 patients on the Intensive Arm, Week3, did not have the required measurement. Five patients on the Conventional Arm and Intensive Arm, Month9, did not have the required measurement.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Conventional (Standard) Antihypertensive Therapy | Biomarker of Vascular Dysfunction - TNF-alpha (pg/mL) | Week3 | 0.87 pg/mL |
| Conventional (Standard) Antihypertensive Therapy | Biomarker of Vascular Dysfunction - TNF-alpha (pg/mL) | Month9 | 1.56 pg/mL |
| Intensive Antihypertensive Therapy | Biomarker of Vascular Dysfunction - TNF-alpha (pg/mL) | Week3 | 0.79 pg/mL |
| Intensive Antihypertensive Therapy | Biomarker of Vascular Dysfunction - TNF-alpha (pg/mL) | Month9 | 1.44 pg/mL |
Secondary
Biomarker of Vascular Dysfunction - Von Willebrand Factor (%)
Comparison between randomized treatment arms
Time frame: 3 weeks and 9 months into therapy
Population: Nine patients on the Conventional Arm and 10 on the Intensive Arm, Week3, did not have the required measurement. Four patients on the Conventional Arm and Intensive Arm, Month9, did not have the required measurement.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Conventional (Standard) Antihypertensive Therapy | Biomarker of Vascular Dysfunction - Von Willebrand Factor (%) | Week3 | 195.00 percentage (%) |
| Conventional (Standard) Antihypertensive Therapy | Biomarker of Vascular Dysfunction - Von Willebrand Factor (%) | Month9 | 211.00 percentage (%) |
| Intensive Antihypertensive Therapy | Biomarker of Vascular Dysfunction - Von Willebrand Factor (%) | Week3 | 191.00 percentage (%) |
| Intensive Antihypertensive Therapy | Biomarker of Vascular Dysfunction - Von Willebrand Factor (%) | Month9 | 164.00 percentage (%) |
Secondary
Biomarkers of Vascular Dysfunction - eNO Synthetase (pg/mL)
Comparison between randomized treatment arms
Time frame: 3 weeks and 9 months into therapy
Population: Seven patients on the Conventional Arm and Intensive Arm, Week3, did not have the required measurement. Fourteen patients on the Conventional Arm and Intensive Arm, Month9, did not have the required measurement.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Conventional (Standard) Antihypertensive Therapy | Biomarkers of Vascular Dysfunction - eNO Synthetase (pg/mL) | Week3 | 187.78 pg/mL |
| Conventional (Standard) Antihypertensive Therapy | Biomarkers of Vascular Dysfunction - eNO Synthetase (pg/mL) | Month9 | 193.28 pg/mL |
| Intensive Antihypertensive Therapy | Biomarkers of Vascular Dysfunction - eNO Synthetase (pg/mL) | Week3 | 267.03 pg/mL |
| Intensive Antihypertensive Therapy | Biomarkers of Vascular Dysfunction - eNO Synthetase (pg/mL) | Month9 | 266.53 pg/mL |
Secondary
Blood Pressure Control on Trial
Comparison of repeated systolic and diastolic blood pressure measures between randomized treatment arms
Time frame: first 9 months of therapy
Population: Three patients on the Conventional Arm did not have the required measurement. Four patients on the Intensive Arm did not have the required measurement.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Conventional (Standard) Antihypertensive Therapy | Blood Pressure Control on Trial | Systolic Blood at Pressure at Month9 | 114.00 mmHg |
| Conventional (Standard) Antihypertensive Therapy | Blood Pressure Control on Trial | Diastolic Blood Pressure at Month9 | 70.00 mmHg |
| Intensive Antihypertensive Therapy | Blood Pressure Control on Trial | Systolic Blood at Pressure at Month9 | 117.00 mmHg |
| Intensive Antihypertensive Therapy | Blood Pressure Control on Trial | Diastolic Blood Pressure at Month9 | 74.00 mmHg |
Secondary
Magnetic Resonance Imaging (MRI) of Right and Left Hip and Knee
Comparison between randomized treatment arms on proportions of MRI identified lesions \>= 30%.
Time frame: 3 weeks and 9 months into therapy
Population: Four Conventional Arm patients and 2 Intensive Arm patients did not have Week3 right hip (R hip), left hip (L hip), right knee (R knee) and left knee (L knee) MRI.~Five Conventional and Intensive Arm patients did not have Month9 R hip MRI. Four Conventional Arm patients and 5 Intensive Arm patients did not have a Month9 L hip and R knee MRI.~Three Conventional Arm patients and 5 Intensive Arm patients did not have a Month9 L knee MRI.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Conventional (Standard) Antihypertensive Therapy | Magnetic Resonance Imaging (MRI) of Right and Left Hip and Knee | >=30% at Week3 | 1 Participants |
| Conventional (Standard) Antihypertensive Therapy | Magnetic Resonance Imaging (MRI) of Right and Left Hip and Knee | <30% at Week3 | 20 Participants |
| Conventional (Standard) Antihypertensive Therapy | Magnetic Resonance Imaging (MRI) of Right and Left Hip and Knee | <30% at Month9 | 17 Participants |
| Conventional (Standard) Antihypertensive Therapy | Magnetic Resonance Imaging (MRI) of Right and Left Hip and Knee | >=30% at Month9 | 3 Participants |
| Intensive Antihypertensive Therapy | Magnetic Resonance Imaging (MRI) of Right and Left Hip and Knee | <30% at Month9 | 16 Participants |
| Intensive Antihypertensive Therapy | Magnetic Resonance Imaging (MRI) of Right and Left Hip and Knee | >=30% at Week3 | 2 Participants |
| Intensive Antihypertensive Therapy | Magnetic Resonance Imaging (MRI) of Right and Left Hip and Knee | <30% at Week3 | 21 Participants |
| Intensive Antihypertensive Therapy | Magnetic Resonance Imaging (MRI) of Right and Left Hip and Knee | >=30% at Month9 | 4 Participants |
| Conventional (Standard) Antihypertensive Therapy-MRI-Left Hip | Magnetic Resonance Imaging (MRI) of Right and Left Hip and Knee | <30% at Week3 | 20 Participants |
| Conventional (Standard) Antihypertensive Therapy-MRI-Left Hip | Magnetic Resonance Imaging (MRI) of Right and Left Hip and Knee | >=30% at Month9 | 3 Participants |
| Conventional (Standard) Antihypertensive Therapy-MRI-Left Hip | Magnetic Resonance Imaging (MRI) of Right and Left Hip and Knee | >=30% at Week3 | 1 Participants |
| Conventional (Standard) Antihypertensive Therapy-MRI-Left Hip | Magnetic Resonance Imaging (MRI) of Right and Left Hip and Knee | <30% at Month9 | 18 Participants |
| Intensive Antihypertensive Therapy-MRI-Left Hip | Magnetic Resonance Imaging (MRI) of Right and Left Hip and Knee | >=30% at Month9 | 4 Participants |
| Intensive Antihypertensive Therapy-MRI-Left Hip | Magnetic Resonance Imaging (MRI) of Right and Left Hip and Knee | >=30% at Week3 | 2 Participants |
| Intensive Antihypertensive Therapy-MRI-Left Hip | Magnetic Resonance Imaging (MRI) of Right and Left Hip and Knee | <30% at Week3 | 21 Participants |
| Intensive Antihypertensive Therapy-MRI-Left Hip | Magnetic Resonance Imaging (MRI) of Right and Left Hip and Knee | <30% at Month9 | 16 Participants |
| Conventional (Standard) Antihypertensive Therapy-MRI-Right Knee | Magnetic Resonance Imaging (MRI) of Right and Left Hip and Knee | >=30% at Month9 | 3 Participants |
| Conventional (Standard) Antihypertensive Therapy-MRI-Right Knee | Magnetic Resonance Imaging (MRI) of Right and Left Hip and Knee | <30% at Month9 | 18 Participants |
| Conventional (Standard) Antihypertensive Therapy-MRI-Right Knee | Magnetic Resonance Imaging (MRI) of Right and Left Hip and Knee | >=30% at Week3 | 1 Participants |
| Conventional (Standard) Antihypertensive Therapy-MRI-Right Knee | Magnetic Resonance Imaging (MRI) of Right and Left Hip and Knee | <30% at Week3 | 20 Participants |
| Intensive Antihypertensive Therapy-MRI-Right Knee | Magnetic Resonance Imaging (MRI) of Right and Left Hip and Knee | <30% at Week3 | 22 Participants |
| Intensive Antihypertensive Therapy-MRI-Right Knee | Magnetic Resonance Imaging (MRI) of Right and Left Hip and Knee | >=30% at Week3 | 1 Participants |
| Intensive Antihypertensive Therapy-MRI-Right Knee | Magnetic Resonance Imaging (MRI) of Right and Left Hip and Knee | <30% at Month9 | 16 Participants |
| Intensive Antihypertensive Therapy-MRI-Right Knee | Magnetic Resonance Imaging (MRI) of Right and Left Hip and Knee | >=30% at Month9 | 4 Participants |
| Conventional (Standard) Antihypertensive Therapy-MRI-Left Knee | Magnetic Resonance Imaging (MRI) of Right and Left Hip and Knee | >=30% at Week3 | 1 Participants |
| Conventional (Standard) Antihypertensive Therapy-MRI-Left Knee | Magnetic Resonance Imaging (MRI) of Right and Left Hip and Knee | <30% at Week3 | 20 Participants |
| Conventional (Standard) Antihypertensive Therapy-MRI-Left Knee | Magnetic Resonance Imaging (MRI) of Right and Left Hip and Knee | >=30% at Month9 | 3 Participants |
| Conventional (Standard) Antihypertensive Therapy-MRI-Left Knee | Magnetic Resonance Imaging (MRI) of Right and Left Hip and Knee | <30% at Month9 | 19 Participants |
| Intensive Antihypertensive Therapy-MRI-Left Knee | Magnetic Resonance Imaging (MRI) of Right and Left Hip and Knee | >=30% at Month9 | 4 Participants |
| Intensive Antihypertensive Therapy-MRI-Left Knee | Magnetic Resonance Imaging (MRI) of Right and Left Hip and Knee | >=30% at Week3 | 1 Participants |
| Intensive Antihypertensive Therapy-MRI-Left Knee | Magnetic Resonance Imaging (MRI) of Right and Left Hip and Knee | <30% at Week3 | 22 Participants |
| Intensive Antihypertensive Therapy-MRI-Left Knee | Magnetic Resonance Imaging (MRI) of Right and Left Hip and Knee | <30% at Month9 | 16 Participants |
Secondary
Rate of Clinically Significant Osteonecrosis
CTCAE grade 2 or high osteonecrosis
Time frame: any time during leukemia therapy, approximately 2.5 years
Secondary
Rate of Clinically Significant Osteonecrosis vs. Historical Control
CTCAE grade 2 or high osteonecrosis vs. Total 16 matched controls
Time frame: any time during leukemia therapy, approximately 2.5 years