Vaccine Response After Cancer Therapy in Pediatric Patients

Overseen By Sceria Jenkins, RN

Age: < 65

Sex: Any

Trial Phase: Phase 2

Sponsor: Atrium Health

Disqualifiers: Immunodeficiency, Pregnancy, Severe infection, 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: 6

64 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines the effectiveness of vaccines for children who have completed cancer treatment. It aims to determine if administering vaccines earlier, three months post-treatment, enhances protection against infections. The trial will compare two vaccination methods: single booster shots versus a full series of shots. Children who have recently completed systemic cancer therapy and may be at risk for infections are suitable candidates for this study. As a Phase 2 trial, this research focuses on evaluating the treatment's effectiveness in an initial, smaller group, providing an opportunity to contribute to significant findings in pediatric cancer recovery.

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 team or your doctor.

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

Research shows that vaccines are generally safe for children who have survived cancer, although their responses can vary. Studies indicate that most children develop a strong immune response after receiving a single booster vaccine. However, not all children respond the same way, and some might need an extra dose for better protection. In one study, children who received a third dose of a COVID-19 vaccine showed a higher response rate.

For the staged revaccination series, evidence suggests that many children achieve protective levels against diseases like tetanus after revaccination. Specifically, one study found that 82.6% of children had sufficient antibodies to protect against tetanus after receiving their shots again. Safety data from various studies show that vaccines are well-tolerated, with no major safety concerns reported, meaning any side effects are usually mild.

Overall, both methods of revaccination appear safe for children who have completed cancer treatment. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about this trial because it explores how pediatric cancer patients respond to vaccines after undergoing cancer therapy, a critical area with limited data. This trial is unique as it compares two approaches: Arm A focuses on delivering single booster doses based on initial titer levels, while Arm B employs a staged revaccination series for those with low baseline titers. This approach helps tailor vaccination strategies to individual needs, potentially offering better protection for vulnerable patients who have completed cancer treatment. By assessing the efficacy of these tailored vaccine strategies, the trial aims to improve long-term immunity in pediatric cancer survivors.

What evidence suggests that this trial's treatments could be effective for pediatric cancer survivors?

Research has shown that many children who survive cancer have weaker immune systems after treatment, increasing their risk of infections. Studies suggest that booster vaccines can help these children regain immunity. For instance, after treatment, 67% to 71% of children were protected against diseases like tetanus and measles, but fewer were protected against infections like hepatitis B.

In this trial, participants will be randomized into different treatment arms to evaluate the effectiveness of vaccination strategies. Arm A will test single booster shots, while Arm B will test a full revaccination series. Both methods aim to determine which best helps these children strengthen their defenses against serious diseases. ^{1 2 6 7 8}

Who Is on the Research Team?

Ashley Hinson, MD

Principal Investigator

Wake Forest University Health Sciences

Are You a Good Fit for This Trial?

This trial is for pediatric cancer survivors aged 2-21 who've finished their cancer therapy within the last 60 days. They should be able to perform daily activities (with some assistance if needed) and comply with study procedures. It's not for those treated only with surgery or radiotherapy, with severe vaccine allergies, immune deficiencies, pregnancy, or active severe infections.

Inclusion Criteria

Written informed consent, HIPAA authorization for release of personal health information, and assent, when applicable from the subject, parent, or legal guardian

My cancer was confirmed by tests and is being treated by Levine Children's Hospital.

I have had cancer before and received at least one round of treatment for it.

Exclusion Criteria

My cancer was treated with only surgery, radiation, or monitoring.

You have had a serious allergic reaction to a vaccine or any of its ingredients in the past.

I do not have a severe infection right now.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Baseline Assessment

Lab evaluations for immune function at baseline

1 visit

1 visit (in-person)

Vaccination Phase

Participants receive either single booster vaccines or a full revaccination series starting at 3 months post therapy

3-9 months

3 visits (in-person) at 3, 6, and 9 months

Follow-up

Participants are monitored for immune response and infection rates at 12 and 24 months post therapy

24 months

2 visits (in-person) at 12 and 24 months

What Are the Treatments Tested in This Trial?

Interventions

• Vaccine

Trial Overview The study evaluates how well pediatric cancer survivors' immune systems work after treatment and how they respond to vaccinations given earlier than usual—at just 3 months post therapy. The goal is to see if this timing or revaccination can better protect against serious infections.

How Is the Trial Designed?

Group I: Arm B - Staged revaccination series Experimental Treatment 1 Intervention

Those subjects randomized to Arm B, the full revaccination series, will receive applicable vaccines when titers are low (below normal range) at baseline. When indicated, non-live vaccines will be given at the 3, 6, and 9 month visits, live vaccines will be given at the 6 and 9 month visit. Subjects who have negative/undetectable titers to any vaccine at the 24 month visit will receive boosters to each applicable vaccine.

Group II: Arm A - Single booster vaccines Experimental Treatment 1 Intervention

Those subjects randomized to Arm A, single dose vaccine boosters, will receive non live vaccine boosters at the 3 month visit. Boosters for live vaccines will be given at the 6 month visit. Boosters will only be given as applicable for low titers tested at the baseline assessment visit. Subjects who have negative/undetectable titers to any vaccine at the 24 month visit will receive boosters to each applicable vaccine.

Who Is Running the Clinical Trial?

Atrium Health

Lead Sponsor

Trials

122

Recruited

34,900+

Wake Forest University Health Sciences

Lead Sponsor

Trials

1,432

Recruited

2,506,000+

Atrium Health Levine Cancer Institute

Collaborator

Trials

30

Recruited

4,700+

Published Research Related to This Trial

In a study of 46 children with cancer, those who had received chemotherapy or immunotherapy for more than 6 weeks before vaccination showed a significantly higher response to the COVID-19 vaccine, with 94.4% achieving good T-cell responses.

A third dose of the vaccine increased the antibody response in patients treated for less than 6 weeks, raising the percentage of good antibody responders from 39.3% to 70%, highlighting the importance of booster doses for this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immune Response following BNT162b2 mRNA COVID-19 Vaccination in Pediatric Cancer Patients. Schmidt, KLJ., Dautzenberg, NMM., Hoogerbrugge, PM., et al.[2023]

Children with cancer often have weakened immune systems due to their illness and intensive chemotherapy, which can affect their response to vaccines.

This review emphasizes the need for tailored vaccination programs for these children, as current data on the safety and efficacy of standard vaccines in this population is limited, highlighting a gap that requires further research.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Vaccinations in children with cancer. Esposito, S., Cecinati, V., Brescia, L., et al.[2010]

In a study of 78 children with cancer, only 26.9% showed a seroconversion response to hepatitis B vaccination after receiving a higher dose of the vaccine during chemotherapy, compared to 100% in healthy controls, indicating a significantly impaired immune response in the cancer group.

By the 12th month of follow-up, only 31.9% of children with cancer had protective antibody levels, suggesting that the current vaccination strategy is insufficient and highlighting the need for more effective vaccines or booster strategies for this vulnerable population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Seroconversion in response to a reinforced primary hepatitis B vaccination in children with cancer]. Villena, R., Zubieta, M., Hurtado, C., et al.[2016]

A response-based re-vaccination schedule for non-transplant pediatric cancer survivors was tested, showing that most patients developed protective antibody levels after receiving vaccines 3 months post-treatment.

This approach suggests that vaccination can be effectively tailored to the individual immune recovery of pediatric cancer survivors, enhancing their protection against infections.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dynamic re-immunization of off-treatment childhood cancer survivors: An implementation feasibility study. Han, JH., Harmoney, KM., Dokmeci, E., et al.[2018]

In a study involving 56 children who had completed chemotherapy, those who received a DTP booster vaccination showed a significant and sustained increase in protective antibody levels compared to the control group.

Despite high baseline immunity to diphtheria, tetanus, and pertussis, a notable percentage of children remained susceptible to measles, mumps, rubella, and hepatitis B, highlighting the importance of booster vaccinations post-chemotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Humoral immune response after post-chemotherapy booster diphtheria-tetanus-pertussis vaccine in pediatric oncology patients. Cheng, FW., Leung, TF., Chan, PK., et al.[2008]

In pediatric cancer patients undergoing chemotherapy, a higher absolute lymphocyte count before vaccination is associated with a better immune response to the H1N1 influenza vaccine.

This study highlights the importance of monitoring lymphocyte levels in predicting vaccination efficacy, which can help optimize vaccination strategies for vulnerable populations like children with cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Absolute lymphocyte count predicts the response to new influenza virus H1N1 vaccination in pediatric cancer patients. Mavinkurve-Groothuis, AM., van der Flier, M., Stelma, F., et al.[2021]

Children undergoing cancer treatment may experience a loss of immunity from prior vaccinations, particularly for diseases like varicella, influenza, and hepatitis B, which can lead to diminished responses to vaccines during and after therapy.

While inactivated vaccines (like those for tetanus and diphtheria) are generally safe and effective in this population, live attenuated vaccines pose significant risks and should be used cautiously, as they can lead to morbidity in immunocompromised children.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Active immunization of children with leukemia and other malignancies. Ridgway, D., Wolff, LJ.[2019]

In a study of 26 pediatric oncology patients, only 36.4% showed an adequate B-cell response and 77.8% showed an adequate T-cell response after SARS-CoV-2 vaccination, indicating a suboptimal immune response in this vulnerable population.

The study suggests that booster doses will be necessary for better protection against COVID-19 in these patients, and that monitoring blood counts may not effectively guide the timing of these boosters.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

SARS-CoV-2 vaccination response in pediatric oncology patients. D'Souza, AM., Thomas, M., Gnanamony, M., et al.[2023]

Children with acute lymphocytic leukemia (ALL) experience a temporary reduction in specific antibody levels after intensified chemotherapy, with protection levels for various vaccines ranging from 17% to 100%.

Most children showed a positive response to revaccination, indicating that while chemotherapy affects immunity, their immunological memory is preserved and can be restored with additional vaccinations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Loss of antibodies and response to (re-)vaccination in children after treatment for acute lymphocytic leukemia: a systematic review. van Tilburg, CM., Sanders, EA., Rovers, MM., et al.[2018]

In a study of 45 children aged 1-18 with solid tumors undergoing or recently completed chemotherapy, the influenza vaccine significantly increased antibody levels, demonstrating a strong immune response post-vaccination.

The study found that 86-97% of the children achieved protective antibody levels after receiving two doses of the vaccine, suggesting that annual vaccination is beneficial for this vulnerable population to prevent influenza-related complications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Assessment of the immune response to trivalent split influenza vaccine in children with solid tumors. Bektas, O., Karadeniz, C., Oguz, A., et al.[2009]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12399832/

Immune Reconstitution and Need for Booster Vaccinations ... Most patients recover immune function by 6 months after therapy; however, some remain deficient for years [1, 16]. Infectious complications, ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12197624/

Deficits in Long-Term Vaccine Immunity Among Childhood ... Following completed cancer therapy, revaccination of the most intensely treated patients with a DTP vaccine was seen in 98 of 146 (67.1%) of ...

3. cancer.gov cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2024-06507

Single Booster Versus Full Revaccination After Completion ... This phase II trial compares the effect of a single booster vaccination versus full revaccination of pediatric cancer patients with abnormal vaccine ...

4. sciencedirect.com sciencedirect.com/science/article/pii/S2468124520300425

Immunisation in children with cancer treated with standard ... The improving outcome of childhood cancers has led to increase in number of survivors needing comprehensive care during and after treatment of cancer.

5. journals.lww.com journals.lww.com/jpho-online/fulltext/2024/01000/vaccine_immunity_in_children_after_hematologic.15.aspx

Vaccine Immunity in Children After Hematologic Cancer... At the end of chemotherapy, 67% to 71% of patients were protected against tetanus, varicella, and measles; 40% remained protected against hepatitis B; and 27% ...

6. onlinelibrary.wiley.com onlinelibrary.wiley.com/doi/abs/10.1002/pbc.28565

Vaccination in pediatric cancer survivors: Vaccination rates ... Most childhood cancer survivors resume vaccinations postchemotherapy. Considerable variability exists in vaccination timing after chemotherapy.

7. publications.aap.org publications.aap.org/pediatrics/article/156/3/e2024070209/203030/Immune-Response-to-COVID-19-Vaccination-in

Immune Response to COVID-19 Vaccination in Children ... Most, not all, children with cancer developed neutralizing antibodies after COVID-19 vaccination. A third dose increased response rate.

8. mdpi.com mdpi.com/2076-393X/13/6/617

Deficits in Long-Term Vaccine Immunity Among Childhood ... Our findings reveal that vaccines are underutilized among CCSs. There was considerable variability in the rates of revaccination based on the type of malignancy ...