Antihypertensive Therapy for Leukemia

No longer 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests two approaches to managing high blood pressure in children and young adults undergoing treatment for newly diagnosed acute lymphoblastic leukemia, a type of blood cancer. The goal is to determine if more intensive blood pressure control can reduce the risk of osteonecrosis, a condition where bone tissue dies due to lack of blood supply. Participants are divided into two groups: one receiving intensive antihypertensive therapy and the other receiving conventional antihypertensive therapy. This trial suits those diagnosed with acute lymphoblastic leukemia or lymphoma who have started but not completed their initial treatment. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that intensive blood pressure treatment, which aims to lower blood pressure more aggressively, is generally well-tolerated. Studies have found that patients receiving this intensive treatment did not experience significantly different outcomes compared to those who did not, suggesting it is reasonably safe. For cancer survivors, in particular, intensive blood pressure control reduced the risk of heart problems without a noticeable increase in side effects.

High blood pressure can cause heart damage in cancer patients, affecting 33-68% of them. This underscores the importance of managing blood pressure carefully. While no clear evidence links blood pressure medication directly to cancer, studies on this topic remain inconclusive.

This trial tests both intensive and regular blood pressure treatments. Although safety data from other trials is promising, especially for intensive treatment, potential participants should consider their personal health conditions and discuss them with a healthcare provider. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about this trial because it explores whether intensive antihypertensive therapy can better manage blood pressure in leukemia patients undergoing treatment. Unlike conventional antihypertensive therapies that aim for higher blood pressure targets, this approach targets lower, more precise blood pressure ranges based on age, sex, and height. The goal is to see if more tightly controlled blood pressure can lead to better overall outcomes during intense treatment phases like remission induction and reinduction. By refining blood pressure management, researchers hope to improve the effectiveness and safety of leukemia treatments.

What evidence suggests that this trial's antihypertensive therapies could be effective for preventing osteonecrosis in leukemia patients?

Research shows that managing blood pressure more carefully might lower the risk of problems like bone tissue death (osteonecrosis) in patients with acute lymphoblastic leukemia (ALL). Studies in similar conditions suggest that maintaining blood pressure within a specific range can lead to better health outcomes. This trial will compare two approaches: Intensive Antihypertensive Therapy, which aims for a more stringent blood pressure target, and Conventional Antihypertensive Therapy, which follows standard targets. Although direct evidence on preventing osteonecrosis in ALL is limited, better blood flow may help protect bone health. Therefore, the trial will test if intensive blood pressure control can reduce the chances of developing osteonecrosis during ALL treatment. ^{6 7 8 9 10}

Who Is on the Research Team?

Seth E. Karol, MD

Principal Investigator

St. Jude Children's Research Hospital

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12050940/

Outcomes with intensive treatment for acute myeloid ... While survival of AML elderly patients remains poor, patients ≥60 years old overall have a 20% survival benefit at 5 years if they receive an alloHCT. While ...

2. nature.com nature.com/articles/s41375-025-02789-y

Intensive chemotherapy for high-risk acute lymphoblastic ... Among these, 53% (N = 10) achieved MRD < 0.1% at EOI, 26% (N = 5) had undetectable MRD, and three patients had no MRD data available. After ...

3. ashpublications.org ashpublications.org/blood/article/143/19/1903/514806/Management-of-ALL-in-adults-2024-ELN

Management of ALL in adults: 2024 ELN recommendations ... The primary end point, achievement of a complete molecular remission (CMR) after 1 cycle, was achieved in 78%. Furthermore, a favorable median survival of 36.5 ...

4. jhoonline.biomedcentral.com jhoonline.biomedcentral.com/articles/10.1186/s13045-023-01409-5

The evolution of acute lymphoblastic leukemia research and ... The CALGB trial showed a 3-year survival rate of 73%. Hyper-CVAD-based therapy (also a pediatric-inspired regimen developed in 1992, and which ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5520400/

Acute lymphoblastic leukemia: a comprehensive review and ... A second phase 2 study of 35 patients with CD22+ ALL in second salvage or later showed similar complete response rate (66%) and median overall survival (7.4 ...

6. ahajournals.org ahajournals.org/doi/10.1161/HYPERTENSIONAHA.123.22194?doi=10.1161/HYPERTENSIONAHA.123.22194

Effect of Intensive Blood Pressure Control on ... Intensive blood pressure control reduced risk of the primary cardiovascular outcome similarly for cancer survivors (hazard ratio, 0.70 [95% CI, ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10882584/

Long-term outcomes in patients with chronic lymphocytic ... Ibrutinib is an effective treatment for patients with chronic lymphocytic leukemia. Ibrutinib is a well tolerated therapy, however hypertension ...

8. withpower.com withpower.com/trial/phase-3-leukemia-9-2020-921d9

Antihypertensive Therapy for Leukemia · Info for Participants Hypertensive cardiotoxicity, which can occur in 33-68% of cancer patients undergoing treatment, is a significant side effect of both conventional and novel ...

9. thelancet.com thelancet.com/journals/lanonc/article/PIIS1470-2045(21)00033-4/fulltext

Antihypertensive treatment and risk of cancer: an individual ... Some studies have suggested a link between antihypertensive medication and cancer, but the evidence is so far inconclusive. Thus, we aimed to investigate ...

10. nejm.org nejm.org/doi/full/10.1056/NEJMoa1611179

Effect of Intensive Blood-Pressure Treatment on Patient ... Patient-reported outcomes among participants who received intensive treatment, which targeted a systolic blood pressure of less than 120 mm Hg, were similar