PEACH TRIAL- Precision Medicine and Adoptive Cellular Therapy

NCT04837547 | Active Not Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: BCC017
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 3

Brief Summary

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)).

Conditions

Neuroblastoma; Diffuse Intrinsic Pontine Glioma

Outcome Measures

Primary Outcomes (1)

• Number of Participants with Dose Limiting Toxicities as a Measure of Safety and Tolerability

  To evaluate the dose-limiting toxicities (DLTs) and to establish the maximum tolerated dose (MTD) of treating children with molecular targeted therapy in combination with adoptive cellular therapy

  2 years

Secondary Outcomes (5)

• Number of Participants with Adverse Events as a Measure of Safety and Tolerability

  2 years plus 30 days

• Number of Participants that are able to have vaccine produced and delivered

  2 years

• Number of participants with progression free survival (PFS) during study

  7 years

• Number of participants with overall survival (OS) during study

  7 years

• Determine the Overall Response Rate (ORR) of Participants using INSS Response Evaluation Criteria for NB and RANO criteria for DIPG

  2 years

Study Arms (2)

Arm 1: Subjects with Diffuse Intrinsic Pontine Glioma (DIPG).

EXPERIMENTAL

This Phase I study is will utilize a standard 3+3 dose escalation design to establish the MTD and will evaluate the following three pre-specified dose levels of xALT: Dose Level 1: 3 x10\^7 cells/kg Dose Level +1: 3 x10\^8 cells/kg Dose Level -1: 3 x10\^6 cells/kg The dose escalation scheme will be evaluated for Arm 1 and Arm 2 separately. For each Study Arm, a minimum of 4 DLT evaluable subjects and a maximum of 12 DLT evaluable subjects will be enrolled (a total of 8 to 24 DLT evaluable subjects).

Biological: Tumor-specific ex vivo expanded autologous lymphocyte transfer (TTRNA-xALT)

Arm 2: Relapsed/Refractory Neuroblastoma (NB)

EXPERIMENTAL

This Phase I study is will utilize a standard 3+3 dose escalation design to establish the MTD and will evaluate the following three pre-specified dose levels of xALT: Dose Level 1: 3 x10\^7 cells/kg Dose Level +1: 3 x10\^8 cells/kg Dose Level -1: 3 x10\^6 cells/kg The dose escalation scheme will be evaluated for Arm 1 and Arm 2 separately. For each Study Arm, a minimum of 4 DLT evaluable subjects and a maximum of 12 DLT evaluable subjects will be enrolled (a total of 8 to 24 DLT evaluable subjects).

Biological: Tumor-specific ex vivo expanded autologous lymphocyte transfer (TTRNA-xALT)

Interventions

Tumor-specific ex vivo expanded autologous lymphocyte transfer (TTRNA-xALT) BIOLOGICAL

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 vivo.

Also known as: xALT

Arm 1: Subjects with Diffuse Intrinsic Pontine Glioma (DIPG).; Arm 2: Relapsed/Refractory Neuroblastoma (NB)

Eligibility Criteria

• Age: 1 Year - 30 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Beat Childhood Cancer Research Consortium: collaborator
• University of Florida: lead

Study Sites (3)

University of Florida

Gainesville, Florida, 32611, United States

Location

Levine Children's Hospital

Charlotte, North Carolina, 28204, United States

Location

Penn State Milton S. Hershey Medical Center and Children's Hospital

Hershey, Pennsylvania, 17033, United States

Location

Related Links

• Beat Childhood Cancer Consortium website

MeSH Terms

Conditions

Neuroblastoma; Diffuse Intrinsic Pontine Glioma

Condition Hierarchy (Ancestors)

Neuroectodermal Tumors, Primitive, Peripheral; Neuroectodermal Tumors, Primitive; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue; Glioma; Brain Stem Neoplasms; Infratentorial Neoplasms; Brain Neoplasms; Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Study Officials

• Giselle Sholler, MD

  Beat Childhood Cancer at Penn State University

  STUDY CHAIR

• Duane Mitchell, M.D., Ph.D.

  University of Florida

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 6, 2021
• First Posted: April 8, 2021
• Study Start: September 20, 2021
• Primary Completion (Estimated): September 1, 2027
• Study Completion (Estimated): September 1, 2032
• Last Updated: April 28, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (3)