Precision medicine and cell therapy for children with brain and neuroblastoma cancers

PEACH TRIAL- Precision mEdicine and Adoptive Cellular tHerapy for the Treatment of Recurrent Neuroblastoma and Newly Diagnosed Diffuse Intrinsic Pontine Glioma (DIPG)

This study is testing a new treatment that combines targeted therapy with immune cell therapy to see if it helps children with tough brain cancers like DIPG and neuroblastoma.

Quick facts

• Phase: Phase 1
• Study type: Interventional
• Enrollment: 24 (estimated)
• Ages: 1 Year to 30 Years
• Sex: All
• Sponsor: University of Florida (Academic / other)
• Drugs / interventions: chemotherapy, radiation
• Locations: 3 sites (Gainesville, Florida and 2 other locations)
• Trial ID: NCT04837547 on ClinicalTrials.gov

What this trial studies

This Phase I open-label, multicenter study aims to evaluate the safety, feasibility, and maximum tolerated dose of a novel treatment combining molecular targeted therapy with adoptive cell therapy for children diagnosed with Diffuse Intrinsic Pontine Glioma (DIPG) or recurrent neuroblastoma. The approach involves using tumor mRNA-pulsed autologous dendritic cells and tumor-specific expanded lymphocytes to enhance the immune response against the cancer. Participants will undergo biopsy to obtain tumor material for the treatment, which is designed for patients with high-risk or refractory conditions. The study will assess the effectiveness of this innovative therapy in a pediatric population.

Who should consider this trial

Good fit: Ideal candidates include children aged 3 to 30 years with newly diagnosed DIPG or recurrent neuroblastoma who have no effective curative therapy options.

Not a fit: Patients with cancers that are not high-risk neuroblastoma or DIPG, or those who do not meet the age or biopsy consent criteria, may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could provide a new therapeutic option for children with aggressive brain tumors and neuroblastoma, potentially improving survival rates.

How similar studies have performed: While this approach is innovative, similar studies combining targeted therapies with adoptive cell therapies have shown promise in other cancers, suggesting potential for success in this context.

Eligibility criteria

Inclusion Criteria:

* Subjects must have proven pediatric cancer with confirmation at diagnosis or at the time of recurrence/progression and clinical determination of disease for which there is no known effective curative therapy or disease that is refractory to established proven therapies fitting into one of the following categories:
* Disease Status:

High Risk Neuroblastoma-

1. Patients that have relapsed following standard of care therapy or having progressed during standard of care therapy and non-responsive/progressive to accepted curative chemotherapy.
2. Neuroblastoma must be age \>12 months at enrollment

Diffuse Intrinsic Pontine (or other brain stem) Glioma

1. Newly-diagnosed patients willing to undergo biopsy
2. Must be within 2 months of diagnosis and prior to starting radiation
3. DIPG must be ≥ 3 years of age at enrollment

   * All subjects must be age ≤ 30 years at enrollment
   * Patient and/or parents/guardian willing to consent to biopsy for obtaining tumor material for confirmatory diagnosis and/or tumor RNA extraction and amplification.
   * Subjects must have measurable disease as defined Per section 8 at the time of biopsy and tumor must be accessible for biopsy. Tumor samples submitted for analysis must contain \>30% viable tumor tissue to qualify. In addition, subjects with NB disease confined to the bone marrow are eligible to enroll if the degree of marrow involvement is expected to be \>30%.
   * Current disease state must be one for which there is currently no known effective therapy
   * Specimens will be obtained only in a non-significant risk manner and not solely for the purpose of investigational testing.
   * Lansky or Karnofsky Score must be ≥ 60
   * Bone Marrow:

     1. ANC (Absolute neutrophil count) ≥ 1000/µl (unsupported)
     2. Platelets ≥ 100,000/µl (can be transfused)
     3. Hemoglobin \> 8 g/dL (can be transfused)
   * Renal: Serum creatinine ≤ upper limit of institutional normal.
   * Adequate liver function must be demonstrated, defined as:

     1. Total bilirubin ≤ 1.5 x upper limit of normal (ULN) for age AND
     2. ALT (SGPT) ≤ 3 times upper limit of normal (ULN) for age
     3. AST (SGOT) ≤ 3 times upper limit of normal (ULN) for age.
   * Subjects with CNS disease currently taking steroids must have been on a stable dose of steroids for at least one week prior to their biopsy and must not have progressive hydrocephalus at enrollment.
   * A negative serum pregnancy test is required for female participants of childbearing potential (≥13 years of age or after onset of menses)
   * Both male and female post-pubertal study subjects need to agree to use one of the more effective birth control methods during treatment and for six months after treatment is stopped. These methods include total abstinence (no sex), oral contraceptives ("the pill"), an intrauterine device (IUD), levonorgestrel implants (Norplant), or medroxyprogesterone acetate injections (Depo-provera shots). If one of these cannot be used, contraceptive foam with a condom is recommended.
   * Informed Consent: All subjects and/or legal guardians must sign informed written consent. Assent, when appropriate, will be obtained according to institutional guidelines
   * Post-Biopsy: Patients with post-biopsy neurological deficits should have deficits that are stable for a minimum of 1 week prior to registration.

Exclusion Criteria:

* Absence of tumor on biopsy specimen or a diagnosis other than NBL or glioma on biopsy
* Known autoimmune or immunosuppressive disease or human immunodeficiency virus infection.
* Subjects with significant renal, cardiac, pulmonary, hepatic or other organ dysfunction.
* Prior allergic reaction to GM-CSF or Td.
* Subjects who have received any cytotoxic chemotherapy within the last 7 days prior to biopsy or focal radiotherapy in the case of patients with diffuse intrinsic pontine (or other brain stem) gliomas
* Subjects with NBL who have received any radiotherapy to the primary sample site within the last 14 days (radiation may be included in treatment decision after biopsy).
* Subjects receiving any investigational drug concurrently.
* Subjects with uncontrolled serious infections or a life-threatening illness (unrelated to tumor)
* Subjects with any other medical condition, including malabsorption syndromes, mental illness or substance abuse, deemed by the Investigator to be likely to interfere with the interpretation of the results or which would interfere with a subject's ability to sign or the legal guardian's ability to sign the informed consent, and subject's ability to cooperate and participate in the study

Where this trial is running

Gainesville, Florida and 2 other locations

• University of Florida — Gainesville, Florida, United States (Recruiting)
• Levine Children's Hospital — Charlotte, North Carolina, United States (Active_not_recruiting)
• Penn State Milton S. Hershey Medical Center and Children's Hospital — Hershey, Pennsylvania, United States (Recruiting)

Study contacts

• Study coordinator: G Bergendahl, MSN

Conditions Neuroblastoma; Diffuse Intrinsic Pontine Glioma