PEACH TRIAL- Precision Medicine and Adoptive Cellular Therapy

Official title

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

Overview

A Phase I open-label, multicenter study, to evaluate the safety, feasibility, and maximum tolerated dose (MTD) of treating children with newly diagnosed DIPG or recurrent neuroblastoma with molecular targeted therapy in combination with adoptive cell therapy (Total tumor mRNA-pulsed autologous Dendritic Cells (DCs) (TTRNA-DCs), Tumor-specific ex vivo expanded autologous lymphocyte transfer (TTRNA-xALT) and Autologous G-CSF mobilized Hematopoietic Stem Cells (HSCs)).

Interventions

• Biological Tumor-specific ex vivo expanded autologous lymphocyte transfer (TTRNA-xALT)
  There will be two immunotherapy products manufactured and administered to subjects enrolled on this trial. The first product will be autologous dendritic cells (DCs) loaded with total tumor messenger ribonucleic acid (mRNA) (TTRNA) derived from malignant tumors. The second product will be autologous T lymphocytes stimulated ex vivo against TTRNA antigens for autologous transfer (TTRNA-xALT). DCs are professional antigen-presenting cells critical for the initiation of B and T-cell responses in vi

Primary outcome measures

• Number of Participants with Dose Limiting Toxicities as a Measure of Safety and Tolerability [Time frame: 2 years]

Secondary outcome measures (5)

• Number of Participants with Adverse Events as a Measure of Safety and Tolerability [Time frame: 2 years plus 30 days]
• Number of Participants that are able to have vaccine produced and delivered [Time frame: 2 years]
• Number of participants with progression free survival (PFS) during study [Time frame: 7 years]
• Number of participants with overall survival (OS) during study [Time frame: 7 years]
• Determine the Overall Response Rate (ORR) of Participants using INSS Response Evaluation Criteria for NB and RANO criteria for DIPG [Time frame: 2 years]

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-

• 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.
• Neuroblastoma must be age >12 months at enrollment

Diffuse Intrinsic Pontine (or other brain stem) Glioma

• Newly-diagnosed patients willing to undergo biopsy
• Must be within 2 months of diagnosis and prior to starting radiation
• 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 or bone marrow must be accessible for biopsy. Tumor or bone marrow samples submitted for analysis must contain >20% viable tumor tissue to qualify. Note: Subjects with NB who are expected to have no evidence of disease after surgical removal of their tumor are still eligible for this trial if their disease would normally require adjuvant chemotherapy treatment after surgery despite NED status.
• 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:

• ANC (Absolute neutrophil count) ≥ 1000/µl (unsupported- >24 hrs off G-CSF and 7 days off neulasta)
• Platelets ≥ 100,000/µl (can be transfused)
• Hemoglobin > 8 g/dL (can be transfused)
• Renal: Serum creatinine ≤ upper limit of institutional normal.
• Adequate liver function must be demonstrated, defined as:

• Total bilirubin ≤ 1.5 x upper limit of normal (ULN) for age AND
• ALT (SGPT) ≤ 3 times upper limit of normal (ULN) for age
• 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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Non-randomized

Model

Sequential

Masking

Open label

Primary purpose

Treatment

Study locations

United States · 3 centers

• University of Florida — Gainesville
• Levine Children's Hospital — Charlotte
• Penn State Milton S. Hershey Medical Center and Children's Hospital — Hershey

Identifiers

NCT: NCT04837547 · BCC017

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗