Virtual Reality for Acute Lymphoblastic Leukemia

(VIRALL Trial)

Overseen By Alissa Groisser, MD

Age: Any Age

Sex: Any

Trial Phase: Academic

Sponsor: Children's National Research Institute

Disqualifiers: Relapsed, Refractory, Ultrasound guided, others

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

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 20

Duration: Approximately 20 procedures over the course of treatment

40 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

Over 90% of children and adolescents diagnosed with acute lymphoblastic leukemia (ALL) will survive long term. Part of the successful treatment that patients receive is the delivery of chemotherapy directly into their spinal fluid via a spinal tap. This takes place approximately 20 times over the course of treatment. Most children and adolescents receive general anesthesia during this procedure to manage pain and anxiety. It is now understood that general anesthesia contributes to impairments in brain functioning in the long term. Therefore, it is important to identify ways to manage pain and anxiety during these procedures that does not include general anesthesia. The investigators propose to test whether virtual reality (VR: a technology that provides immersive experiences utilizing content uploaded on a headset), used with local anesthesia and the option for an anti-anxiety medication will be an adequate replacement for general anesthesia for participants 7 years of age and over, with ALL in the maintenance phase of treatment.

Will I have to stop taking my current medications?

The trial protocol does not specify whether you need to stop taking your current medications. However, since the focus is on using virtual reality instead of general anesthesia, it seems unlikely that you would need to stop other medications.

Is Virtual Reality Therapy safe for humans?

There is no specific safety data available for Virtual Reality Therapy in the context of acute lymphoblastic leukemia, but general safety information for VR therapy in other conditions suggests it is generally safe for humans. ^{1 2 3 4 5}

How is Virtual Reality Therapy different from other treatments for acute lymphoblastic leukemia?

Virtual Reality Therapy is unique because it uses immersive technology to potentially help manage symptoms and improve the quality of life for patients, rather than directly targeting the leukemia cells like traditional chemotherapy or stem cell transplantation. ^{6 7 8 9 10}

What data supports the effectiveness of the treatment Virtual Reality Therapy for Acute Lymphoblastic Leukemia?

Research shows that virtual reality can help reduce pain and anxiety in children with cancer, including those receiving treatments like chemotherapy. It provides a fun and engaging distraction, making medical procedures less stressful and more comfortable for young patients. ^{11 12 13 14 15}

Are You a Good Fit for This Trial?

This trial is for children and adolescents over 7 years old with acute lymphoblastic leukemia (ALL) who are in the maintenance phase of treatment. They must be scheduled to receive spinal taps as part of their therapy but cannot participate if they have conditions that make VR use unsafe or have had previous adverse reactions to local anesthesia or anti-anxiety medications.

Inclusion Criteria

My initial diagnosis was either ALL or Lymphoma.

I am currently in the maintenance phase of my treatment.

I have 2 more maintenance treatments left.

Exclusion Criteria

My condition has returned or didn't respond to treatment.

Already does LPs without anesthesia

I have had an ultrasound-guided lumbar puncture before.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive intrathecal chemotherapy with pain and anxiety management using VR, local anesthesia, and optional anxiolytics during lumbar punctures

Approximately 20 procedures over the course of treatment

20 visits (in-person)

Follow-up

Participants are monitored for feasibility and acceptability of VR as an alternative to general anesthesia

1-3 months

What Are the Treatments Tested in This Trial?

Interventions

• Virtual Reality

Trial Overview The study is testing whether using a Virtual Reality headset, along with local anesthesia and optional anti-anxiety medication, can effectively manage pain and anxiety during spinal taps, as an alternative to general anesthesia.

How Is the Trial Designed?

Group I: VR Arm Experimental Treatment 1 Intervention

Pain and anxiety management in this arm will include: topical numbing cream 30 minutes prior to the scheduled procedure, option for a 0.05mg/kg (max 2 mg) oral/IV dose of lorazepam. VR headsets will be donned. After sterile cleaning of the lumbar spine area, lidocaine will be injected between L3-4 or L4-5 for local anesthetic. A 22-gauge needle of appropriate length (1.5, 2.5, 3.5 inch) will be used to access the intrathecal space. Cerebral spinal fluid will be collected for evaluation (standard procedure) and IT chemotherapy will be administered.

Group II: GA Arm Active Control 1 Intervention

Pain and anxiety in this arm will be managed with general anesthesia, usually propofol, which is the current standard of care at Children's National Hospital.

Virtual Reality is already approved in United States for the following indications:

Approved in United States as Virtual Reality Therapy for:

• Functional Dyspepsia
• Irritable Bowel Syndrome (IBS)
• Gastroparesis

Who Is Running the Clinical Trial?

Children's National Research Institute

Lead Sponsor

Trials

227

Recruited

258,000+

Rally Foundation for Childhood Cancer Research

Collaborator

Trials

6

Recruited

500+

Rally Foundation for Childhood Cancer Research

Collaborator

Trials

6

Recruited

500+

Published Research Related to This Trial

Virtual reality (VR) interventions have been shown to significantly reduce symptoms of anxiety, depression, pain, and fatigue in cancer patients, based on a meta-analysis of 6 studies.

The findings suggest that while VR is effective for managing acute symptoms during cancer treatment, further research is needed to explore its benefits for long-term side effects in cancer survivorship care.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Meta-Analysis of the Efficacy of Virtual Reality-Based Interventions in Cancer-Related Symptom Management. Zeng, Y., Zhang, JE., Cheng, ASK., et al.[2020]

The study involving 14 children aged 6 to 18 with acute lymphoblastic leukemia (ALL) demonstrated that virtual reality (VR) technology can effectively reduce perceived pain during L-asparaginase (L-ASP) intramuscular injections, with 8 out of 14 patients reporting less pain after using VR.

Caregivers observed that VR not only improved the children's pain perception but also led to less resistance and crying during the procedure, suggesting that VR can enhance the overall experience of painful treatments in pediatric oncology.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immersive Virtual Reality to Distract From Pain in Children Treated With L-asparaginase by Intramuscular Injection. Chiu, CC., Lin, YT., Wang, Y., et al.[2023]

A study involving 90 pediatric oncology patients and their caregivers found that an Immersive VR therapeutic intervention was highly acceptable and satisfactory, with minimal adverse effects reported by patients.

Healthcare professionals expressed favorable perceptions of the VR technology, indicating it was easy to use and useful, suggesting strong potential for future implementation in pediatric oncology settings to improve patient quality of life.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Feasibility, Acceptability, and Clinical Implementation of an Immersive Virtual Reality Intervention to Address Psychological Well-Being in Children and Adolescents With Cancer. Tennant, M., McGillivray, J., Youssef, GJ., et al.[2021]

Virtual reality interventions significantly reduce pain and anxiety in children and adolescents undergoing cancer treatment, with medium effect sizes of 0.60 for anxiety and -0.667 for pain based on a meta-analysis of seven randomized controlled trials.

Age was identified as an important factor influencing the effectiveness of virtual reality for pain management, highlighting the need for further large-scale randomized controlled trials to strengthen the evidence for its use in pediatric oncology.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effectiveness of Virtual Reality in Anxiety and Pain Management in Children and Adolescents Receiving Cancer Treatment: A Systematic Review and Meta-analysis of Randomized Controlled Trials. Ozturk, CS., Toruner, EK.[2023]

Virtual reality (VR) technologies have been found to effectively reduce pain, pulse rates, and distress in pediatric cancer patients during invasive treatments, highlighting its potential as a supportive care tool.

The effectiveness of VR is enhanced by high-fidelity features and personalized experiences, suggesting that tailored VR applications could improve patient comfort and pain management during procedures.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Use of virtual reality in the supportive care management of paediatric patients with cancer. Yap, KY., Koh, DWH., Lee, VSJ., et al.[2021]

A study involving 257 children and adolescents with leukemia and lymphoma revealed that fatigue was the most severe adverse event reported both before and after treatment, affecting 68.1% of participants at the start and 67% after treatment.

Gastrointestinal symptoms, such as nausea and abdominal pain, were also prevalent, with little change in severity or interference over time, indicating that despite supportive care, many children continue to experience significant symptoms during therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Longitudinal use of patient reported outcomes in pediatric leukemia and lymphoma reveals clinically relevant symptomatic adverse events. Jacobs, SS., Withycombe, JS., Castellino, SM., et al.[2022]

A study involving 281 children with acute lymphoblastic leukemia (ALL) showed significant impairments in health-related quality of life (HR-QoL) during the first year of chemotherapy, as reported by both parents and children.

Children receiving intramuscular asparaginase experienced greater treatment and procedural anxiety compared to those receiving intravenous asparaginase, highlighting the impact of treatment type on HR-QoL, particularly during intensive therapy phases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Impairment of health-related quality of life for children with acute lymphoblastic leukemia over the first year of therapy: A report from the DFCI ALL Consortium. Welch, JJG., Flamand, Y., Stevenson, KE., et al.[2023]

In a study involving 34 children aged 10-15 years in long-term remission from acute lymphoblastic leukemia, combined rehabilitation including balneotherapy showed positive effects on heart rate and circulation asymmetry.

The treatment was found to be safe, with no reported side effects, indicating its potential as a beneficial adjunct therapy for these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Experience in using hydrotherapy in children with acute lymphoblastic leukemia at a sanatorium]. Filippov, EG., Bukhny, AF., Finogenova, NA., et al.[2007]

CD19-directed CAR-T cell therapy has shown a remarkable complete remission rate of 94% in patients with refractory/relapsed B-cell acute lymphoblastic leukemia (ALL), significantly outperforming traditional chemotherapy.

Despite its high efficacy, CAR-T therapy is associated with serious complications such as cytokine release syndrome and neurotoxicity, which pose challenges for its clinical application and are linked to high relapse rates.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Advances of CD19-directed chimeric antigen receptor-modified T cells in refractory/relapsed acute lymphoblastic leukemia. Wei, G., Ding, L., Wang, J., et al.[2023]

Acute lymphocytic leukemia (ALL) in children, once a fatal disease, is now curable in nearly half of cases due to extensive research and treatment advancements at St. Jude Children's Research Hospital since 1962.

While survival rates have improved, there is a need to identify 'high-risk' patients who may not respond well to standard treatments, prompting ongoing research to modify therapies for better outcomes while managing long-term treatment-related toxicities.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Childhood acute lymphocytic leukemia: progress and problems in treatment. Bowman, WP.[2018]

Acute lymphoblastic leukemia (ALL) is very responsive to initial chemotherapy, but adult long-term survival rates remain low at under 35% due to high relapse rates, highlighting the need for effective post-remission therapies.

Allogeneic donor stem cell transplantation, particularly using unrelated donor (URD) and umbilical cord blood (UCB) allografts, has shown promise in providing an anti-leukemia effect and improving survival outcomes for patients in their first complete remission.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Unrelated donor allogeneic transplantation for adult acute lymphoblastic leukemia: a review. Bachanova, V., Weisdorf, D.[2008]

Recent advancements in treatment for acute lymphoblastic leukemia (ALL) have significantly improved outcomes, especially for older adults and patients with relapsed or refractory disease, through the introduction of novel therapies.

Emerging treatments include targeted tyrosine kinase inhibitors, immune-based therapies like blinatumomab and inotuzumab ozogamicin, and CAR T cell therapies, which are reshaping the treatment landscape and offering new options at diagnosis and during salvage therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Novel Therapies in the Treatment of Adult Acute Lymphoblastic Leukemia. Gavralidis, A., Brunner, AM.[2022]

Recent advancements in treating acute lymphoblastic leukemia (ALL) include new targeted therapies, particularly in immunotherapy, which are changing the treatment landscape.

Innovative approaches such as antibody-based therapies (including monoclonal antibodies and CAR T cells) are being developed, especially for specific subtypes of ALL, indicating a shift away from traditional chemotherapy towards more personalized treatment options.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Novel Therapies in Acute Lymphoblastic Leukemia. Phelan, KW., Advani, AS.[2022]

A case of isolated ovarian relapse of acute lymphoblastic leukemia occurred 7 years after initial treatment, highlighting the potential for late relapses even in patients who appear to be in remission.

The standard treatment for such relapses involves surgical removal of the ovarian mass followed by chemotherapy, which is consistent with approaches for other types of relapses in this disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Isolated ovarian relapse of pre-B acute lymphoblastic leukemia: a case report. Berretta, R., Barone, A., Rolla, M., et al.[2009]

Acute lymphoblastic leukemia (ALL) can be cured in about one third of adult patients, but treatment outcomes vary widely due to individual clinical and genetic factors, which help determine risk classes for tailored therapies.

Modern treatment approaches, including chemotherapy, stem-cell transplantation, and targeted therapies, are improving long-term survival rates for ALL, with ongoing studies aiming for a cure rate of 50% or more.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Modern therapy of acute lymphoblastic leukemia. Bassan, R., Hoelzer, D.[2022]

Citations

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

Meta-Analysis of the Efficacy of Virtual Reality-Based Interventions in Cancer-Related Symptom Management. [2020]

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

Immersive Virtual Reality to Distract From Pain in Children Treated With L-asparaginase by Intramuscular Injection. [2023]

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

Feasibility, Acceptability, and Clinical Implementation of an Immersive Virtual Reality Intervention to Address Psychological Well-Being in Children and Adolescents With Cancer. [2021]

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

Effectiveness of Virtual Reality in Anxiety and Pain Management in Children and Adolescents Receiving Cancer Treatment: A Systematic Review and Meta-analysis of Randomized Controlled Trials. [2023]

5. England pubmed.ncbi.nlm.nih.gov

Use of virtual reality in the supportive care management of paediatric patients with cancer. [2021]

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

Longitudinal use of patient reported outcomes in pediatric leukemia and lymphoma reveals clinically relevant symptomatic adverse events. [2022]

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

Impairment of health-related quality of life for children with acute lymphoblastic leukemia over the first year of therapy: A report from the DFCI ALL Consortium. [2023]

8. Russia (Federation) pubmed.ncbi.nlm.nih.gov

[Experience in using hydrotherapy in children with acute lymphoblastic leukemia at a sanatorium]. [2007]

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

Advances of CD19-directed chimeric antigen receptor-modified T cells in refractory/relapsed acute lymphoblastic leukemia. [2023]

10. Canada pubmed.ncbi.nlm.nih.gov

Childhood acute lymphocytic leukemia: progress and problems in treatment. [2018]

11. England pubmed.ncbi.nlm.nih.gov

Unrelated donor allogeneic transplantation for adult acute lymphoblastic leukemia: a review. [2008]

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

Novel Therapies in the Treatment of Adult Acute Lymphoblastic Leukemia. [2022]

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

Novel Therapies in Acute Lymphoblastic Leukemia. [2022]

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

Isolated ovarian relapse of pre-B acute lymphoblastic leukemia: a case report. [2009]

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

Modern therapy of acute lymphoblastic leukemia. [2022]