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| Name | Class |
|---|---|
| Beat Childhood Cancer Research Consortium | UNKNOWN |
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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)).
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 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). |
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| 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). |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| 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. |
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| Number of Participants with Adverse Events as a Measure of Safety and Tolerability | To evaluate the overall safety profile of study treatment | 2 years plus 30 days |
| Number of Participants that are able to have vaccine produced and delivered |
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Inclusion Criteria:
High Risk Neuroblastoma-
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:
Renal: Serum creatinine ≤ upper limit of institutional normal.
Adequate liver function must be demonstrated, defined as:
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:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| BCC Enroll | Contact | 717-531-0003 | BCCEnroll@pennstatehealth.psu.edu |
| Name | Affiliation | Role |
|---|---|---|
| Giselle Sholler, MD | Beat Childhood Cancer at Penn State University | Study Chair |
| Duane Mitchell, M.D., Ph.D. | University of Florida | Study Chair |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of Florida | Recruiting | Gainesville | Florida | 32611 | United States |
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| Label | URL |
|---|---|
| Beat Childhood Cancer Consortium website | View source |
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| ID | Term |
|---|---|
| D009447 | Neuroblastoma |
| D000080443 | Diffuse Intrinsic Pontine Glioma |
| ID | Term |
|---|---|
| D018241 | Neuroectodermal Tumors, Primitive, Peripheral |
| D018242 | Neuroectodermal Tumors, Primitive |
| D018302 | Neoplasms, Neuroepithelial |
| D017599 | Neuroectodermal Tumors |
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To evaluable the feasibility of producing and administering the protocol directed therapy
| 2 years |
| Number of participants with progression free survival (PFS) during study | To determine the activity of treatments chosen based on Progression free survival (PFS) | 7 years |
| Number of participants with overall survival (OS) during study | To determine the activity of treatments chosen based on Overall Survival (OS) | 7 years |
| Determine the Overall Response Rate (ORR) of Participants using INSS Response Evaluation Criteria for NB and RANO criteria for DIPG | To determine the activity of treatments chosen based on Overall Response Rate (ORR) | 2 years |
| Levine Children's Hospital | Active, not recruiting | Charlotte | North Carolina | 28204 | United States |
| Penn State Milton S. Hershey Medical Center and Children's Hospital | Recruiting | Hershey | Pennsylvania | 17033 | United States |
|
| D009373 | Neoplasms, Germ Cell and Embryonal |
| D009370 | Neoplasms by Histologic Type |
| D009369 | Neoplasms |
| D009375 | Neoplasms, Glandular and Epithelial |
| D009380 | Neoplasms, Nerve Tissue |
| D005910 | Glioma |
| D020295 | Brain Stem Neoplasms |
| D015192 | Infratentorial Neoplasms |
| D001932 | Brain Neoplasms |
| D016543 | Central Nervous System Neoplasms |
| D009423 | Nervous System Neoplasms |
| D009371 | Neoplasms by Site |
| D001927 | Brain Diseases |
| D002493 | Central Nervous System Diseases |
| D009422 | Nervous System Diseases |