Antihypertensive Therapy for Leukemia

Recruiting at 2 trial locations

Overseen By Seth E. Karol, MD

Age: Any Age

Sex: Any

Trial Phase: Phase 2

Sponsor: St. Jude Children's Research Hospital

Must be taking: Antihypertensives

Disqualifiers: Renal dysfunction, Down's syndrome, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 3

51 Participants Needed

Trial Summary

What is the purpose of this trial?

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.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

What data supports the effectiveness of antihypertensive therapy for leukemia?

Antihypertensive therapy, particularly using renin angiotensin system inhibitors, has been shown to reduce the incidence of arterial thrombotic events in patients with chronic myeloid leukemia and hypertension, suggesting potential benefits in managing blood pressure in leukemia patients. ^{1 2 3 4 5}

Is antihypertensive therapy generally safe for humans?

Antihypertensive drugs are widely used and generally considered safe, with a well-documented benefit for heart health. However, in cancer patients, these drugs can sometimes cause high blood pressure, which needs to be managed carefully during treatment. ^{6 7 8 9 10}

How does Intensive Antihypertensive Therapy differ from other treatments for leukemia?

Intensive Antihypertensive Therapy is unique because it specifically targets high blood pressure, a common complication in leukemia patients, which can be aggravated by the disease and its treatments. This therapy may help manage hypertension that arises due to the leukemic process or as a side effect of chemotherapy, potentially preventing life-threatening complications. ^{2 5 7 11 12}

Research Team

Seth E. Karol, MD

Principal Investigator

St. Jude Children's Research Hospital

Eligibility Criteria

This trial is for children and young adults over 10 years old with newly diagnosed acute lymphoblastic leukemia/lymphoma, who are not hypertensive. They must be able to undergo MRI scans, not have severe kidney issues or growth-altering syndromes, and agree to use contraception if applicable.

Inclusion Criteria

I am 10 years old or older.

I have completed up to 4 days of my current treatment plan.

I am currently being treated for ALL following the TOT17 protocol.

Exclusion Criteria

I cannot walk due to long-term conditions, not because of recent leukemia/lymphoma complications.

My kidney function is significantly reduced.

Inability or unwillingness of research participant or legal guardian/representative to give written informed consent.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Induction Therapy

Patients begin induction therapy and are randomized to either intensive or conventional antihypertensive therapy on day 4.

9 months

Regular visits every 3-4 days for blood pressure adjustments

Reinduction II Therapy

Continuation of antihypertensive therapy until the completion of reinduction II. Patients are evaluated for osteonecrosis using MRI.

Approximately 9 months into therapy

MRI evaluations during reinduction II

Follow-up

Participants are monitored for safety and effectiveness after treatment, including evaluation of osteonecrosis and blood pressure control.

2.5 years

Treatment Details

Interventions

• Conventional Antihypertensive Therapy
• Intensive Antihypertensive Therapy

Trial Overview The study compares intensive antihypertensive therapy (aiming for lower blood pressure targets) versus conventional therapy (higher targets) in reducing osteonecrosis risk during leukemia/lymphoma treatment. It includes surveys, interviews, and monitoring of blood pressure and vascular health.

Participant Groups

Group I: Intensive Antihypertensive Therapy Experimental Treatment 3 Interventions

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.

Group II: Conventional Antihypertensive Therapy Active Control 3 Interventions

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.

Who Is Running the Clinical Trial?

St. Jude Children's Research Hospital

Lead Sponsor

Trials

451

Recruited

5,326,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Findings from Research

Hypertensive cardiotoxicity, which can occur in 33-68% of cancer patients undergoing treatment, is a significant side effect of both conventional and novel cancer therapies, highlighting the need for careful monitoring of blood pressure during treatment.

Interestingly, while hypertension is a common side effect, it can also indicate a positive response to cancer treatment, creating a paradox where managing hypertension is crucial yet may also reflect treatment efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hypertensive Cardiotoxicity in Cancer Treatment-Systematic Analysis of Adjunct, Conventional Chemotherapy, and Novel Therapies-Epidemiology, Incidence, and Pathophysiology. Chung, R., Tyebally, S., Chen, D., et al.[2020]

References

1. England pubmed.ncbi.nlm.nih.gov

Resistance to antihypertensive drugs targeting Renin-Angiotensin-Aldosterone-System in cancer patients: a case series. [2020]

2. England pubmed.ncbi.nlm.nih.gov

High incidence of hypertension in children presenting with acute lymphoblastic leukemia. [2019]

3. Germany pubmed.ncbi.nlm.nih.gov

[Recent intervention studies with antihypertensive drugs and their influence on guidelines]. [2013]

4. Germany pubmed.ncbi.nlm.nih.gov

Renin angiotensin system inhibitors reduce the incidence of arterial thrombotic events in patients with hypertension and chronic myeloid leukemia treated with second- or third-generation tyrosine kinase inhibitors. [2021]

5. United States pubmed.ncbi.nlm.nih.gov

Hypertension in childhood cancer: a frequent complication of certain tumor sites. [2011]

6. England pubmed.ncbi.nlm.nih.gov

Antihypertensive therapy and the risk of malignancies. [2013]

7. United States pubmed.ncbi.nlm.nih.gov

Cardiovascular toxic effects of VM26 in the treatment of acute lymphatic leukemia. Presentation of two cases. [2022]

8. Switzerland pubmed.ncbi.nlm.nih.gov

Hypertensive Cardiotoxicity in Cancer Treatment-Systematic Analysis of Adjunct, Conventional Chemotherapy, and Novel Therapies-Epidemiology, Incidence, and Pathophysiology. [2020]

9. England pubmed.ncbi.nlm.nih.gov

Hypertension in Cardio-Oncology Clinic: an update on etiology, assessment, and management. [2023]

10. United States pubmed.ncbi.nlm.nih.gov

Antihypertensive Drugs and Risk of Cancer: Between Scylla and Charybdis. [2021]

11. United States pubmed.ncbi.nlm.nih.gov

Can renal leukemic infiltration cause hypertension in children? [2011]

12. Israel pubmed.ncbi.nlm.nih.gov

[Multicenter community-based trial of amlodipine in hypertension in Israel]. [2013]