RECRUITING

PEACH TRIAL- Precision Medicine and Adoptive Cellular Therapy

Conditions

Neuroblastoma Diffuse Intrinsic Pontine Glioma

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

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)).

Official Title

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

Quick Facts

Study Start:2021-09-20

Study Completion:2032-09

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT04837547

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:1 Year to 30 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:CHILD, ADULT

Inclusion Criteria	Exclusion 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: 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 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.	* 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

Inclusion Criteria

Exclusion 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:
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
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.

* 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

Contacts and Locations

Study Contact

G Bergendahl, MSN

CONTACT

(704) 355-1220

genevieve.bergendahl@atriumhealth.org

Principal Investigator

Giselle Sholler, MD

STUDY_CHAIR

Beat Childhood Cancer at Atrium Health

Duane Mitchell, M.D., Ph.D.

STUDY_CHAIR

University of Florida

Study Locations (Sites)

University of Florida

Gainesville, Florida, 32611

United States

Levine Children's Hospital

Charlotte, North Carolina, 28204

United States

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

Hershey, Pennsylvania, 17033

United States

Collaborators and Investigators

Sponsor: University of Florida

Giselle Sholler, MD, STUDY_CHAIR, Beat Childhood Cancer at Atrium Health
Duane Mitchell, M.D., Ph.D., STUDY_CHAIR, University of Florida

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2021-09-20

Study Completion Date2032-09

Study Record Updates

Study Start Date2021-09-20

Study Completion Date2032-09

Terms related to this study

Additional Relevant MeSH Terms

Neuroblastoma
Diffuse Intrinsic Pontine Glioma