Pediatric Precision Laboratory Advanced Neuroblastoma Therapy (PEDS-PLAN)

April 24, 2026 updated by: Giselle Sholler

A Study Using Molecular Guided Therapy With Induction Chemotherapy Followed by a Randomized Controlled Trial of Standard Immunotherapy With or Without DFMO Followed by DFMO Maintenance for Subjects With Newly Diagnosed High-Risk Neuroblastoma

A prospective open label, multicenter study to evaluate the feasibility and acute toxicity of using molecularly guided therapy in combination with standard therapy followed by a Randomized Controlled Trial of standard immunotherapy with or without DFMO followed by DFMO maintenance for Subjects with Newly Diagnosed High-Risk Neuroblastoma.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

500

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • Canada
  • United States
    • Alabama
      • Birmingham, Alabama, United States, 35233
        • Recruiting
        • University of Alabama/Children's of Alabama
        • Contact:
        • Principal Investigator:
          • Elizabeth Alva
    • Arkansas
      • Little Rock, Arkansas, United States, 72202
        • Recruiting
        • Arkansas Children's Hospital
        • Principal Investigator:
          • Kevin Bielamowicz
        • Contact:
    • California
      • Oakland, California, United States, 94609
        • Recruiting
        • UCSF Benioff Children's Hospital Oakland
        • Contact:
        • Principal Investigator:
          • Jennifer Michlitsch
      • San Diego, California, United States, 92123
        • Recruiting
        • Rady Children's Hospital
        • Contact:
        • Principal Investigator:
          • William Roberts
    • Connecticut
      • Hartford, Connecticut, United States, 06106
    • Florida
      • Miami, Florida, United States, 33155
      • Orlando, Florida, United States, 32806
      • Tampa, Florida, United States, 33614
        • Recruiting
        • St. Joseph's Children's Hospital
        • Principal Investigator:
          • Don Eslin
        • Contact:
    • Georgia
      • Augusta, Georgia, United States, 30912
        • Recruiting
        • Augusta University Health
        • Contact:
        • Principal Investigator:
          • Coleen McDonough
    • Hawaii
      • Honolulu, Hawaii, United States, 96813
        • Recruiting
        • Kapiolani Medical Center for Women and Children
        • Principal Investigator:
          • Randal Wada
        • Contact:
    • Idaho
      • Boise, Idaho, United States, 83712
        • Completed
        • St. Lukes
    • Illinois
      • Chicago, Illinois, United States, 60453
        • Completed
        • Advocate Aurora Research Institute
    • Kentucky
      • Louisville, Kentucky, United States, 40202
        • Recruiting
        • Norton Children's Research Institute/Affiliated with University of Louisville School of Medicine
        • Principal Investigator:
          • Michael Ferguson
        • Contact:
    • Michigan
      • Grand Rapids, Michigan, United States, 49503
    • Minnesota
      • Minneapolis, Minnesota, United States, 55404
        • Recruiting
        • Children's Hospital and Clinics of Minnesota
        • Contact:
        • Principal Investigator:
          • Jawhar Rawwas
    • Missouri
      • Kansas City, Missouri, United States, 64108
        • Completed
        • Children's Mercy Hospitals and Clinics
      • St Louis, Missouri, United States, 63104
        • Recruiting
        • Cardinal Glennon Children's Medical Center
        • Principal Investigator:
          • William Ferguson
        • Contact:
    • New Jersey
      • Hackensack, New Jersey, United States, 07601
        • Completed
        • Hackensack University Medical Center
    • North Carolina
      • Charlotte, North Carolina, United States, 28204
    • Oregon
      • Portland, Oregon, United States, 97227
        • Recruiting
        • Randall Children's Hospital
        • Contact:
        • Principal Investigator:
          • Jason Glover
    • Pennsylvania
      • Hershey, Pennsylvania, United States, 17033
    • South Carolina
      • Charleston, South Carolina, United States, 29425
        • Recruiting
        • Medical University of South Carolina
        • Principal Investigator:
          • Jaqueline Kraveka
        • Contact:
    • Texas
      • Austin, Texas, United States, 78723
        • Recruiting
        • Dell Children's Blood and Cancer Center
        • Contact:
        • Principal Investigator:
          • Virginia Harrod
      • Dallas, Texas, United States, 75235
        • Recruiting
        • Children's Medical Center
        • Principal Investigator:
          • Tanya Watt
        • Contact:

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.

Eligibility Criteria

Ages Eligible for Study

No older than 18 years (Child, Adult)

Accepts Healthy Volunteers

No

Description

Part A- CLOSED:

  1. Diagnosis: Subjects must have a diagnosis of neuroblastoma or ganglioneuroblastoma (nodular or intermixed) verified by histology or demonstration of clumps of tumor cells in bone marrow with elevated urinary catecholamine metabolites. Subjects with the following disease stages at diagnosis are eligible, if they meet the other specified criteria:

    a) Subjects with newly diagnosed neuroblastoma with INSS Stage 4 are eligible with the following: i. Age > 18 months (> 547 days) regardless of biologic features or ii. Age 12-18 months (365-547 days) with any of the following 3 unfavorable biologic features (MYCN amplification, unfavorable pathology and/or DNA index = 1) or iii. MYCN amplification (> 4-fold increase in MYCN signals as compared to reference signals), regardless of age or additional biologic features.

    b) Subjects with newly diagnosed neuroblastoma with INSS Stage 3 are eligible with the following: i. MYCN amplification (> 4-fold increase in MYCN signals as compared to reference signals), regardless of age or additional biologic features or ii. Age > 18 months (> 547 days) with unfavorable pathology, regardless of MYCN status.

    c) Subjects with newly diagnosed neuroblastoma with INSS Stage 2A/2B with MYCN amplification (> 4-fold increase in MYCN signals as compared to reference signals), regardless of age or additional biologic features.

  2. Subjects must be age ≤ 21 years at initial diagnosis
  3. Subjects must not have had prior systemic therapy except for localized emergency radiation to sites of life-threatening or function-threatening disease and/or no more than 1 cycle of chemotherapy per a low or intermediate risk neuroblastoma regimen (as per P9641, A3961, ANBL0531, or similar) prior to determination of MYCN amplification status and histology.
  4. Specimens will be obtained only in a non-significant risk manner and not solely for the purpose of investigational testing.

  5. Ability to tolerate PBSC collection: No known contraindication to PBSC collection. Examples of contraindications would include a weight or size less than that determined to be feasible at the collecting institution, or a physical condition that would limit the ability of the child to undergo apheresis catheter placement (if necessary) and/or the apheresis procedure.

    Part A and B both- Part A CLOSED, Part B- OPEN:

  6. Adequate Cardiac Function Defined As:

    1. Shortening fraction of ≥ 27% by echocardiogram, or
    2. Ejection fraction of ≥ 50% by radionuclide evaluation or echocardiogram.

  7. Adequate liver function must be demonstrated, defined as:

    c. Total bilirubin ≤ 1.5 x upper limit of normal (ULN) for age AND d. ALT (SGPT) < 10 x upper limit of normal (ULN) for age

  8. Subjects must have adequate renal function defined as a serum creatinine based on age/gender as follows:

    Age Maximum Serum Creatinine (mg/dL) Male Female 1 month to < 6 months 0.4 0.4 6 months to < 1 year 0.5 0.5 1 to < 2 years 0.6 0.6 2 to < 6 year 0.8 0.8 6 to < 10 years 1 1 10 to < 13 years 1.2 1.2 13 to < 16 years 1.5 1.4

    ≥ 16 years 1.7 1.4

  9. A negative serum pregnancy test is required for female participants of child bearing potential (≥13 years of age or after onset of menses)
  10. 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), levonorgestrol implants (Norplant), or medroxyprogesterone acetate injections (Depo-provera shots). If one of these cannot be used, contraceptive foam with a condom is recommended.

  11. Informed Consent: All subjects and/or legal guardians must sign informed written consent. Assent, when appropriate, will be obtained according to institutional guidelines.

    Part B- OPEN:

  12. All patients must have a pathologically confirmed diagnosis of neuroblastoma, be age ≤ 21 years at initial diagnosis, and classified as high risk by the criteria used by COG or SIOPEN at the time of diagnosis. Exception: patients who are initially diagnosed as non-high-risk neuroblastoma, but later converted (and/or relapsed) to high risk neuroblastoma are also eligible.
  13. Previous Therapy- subjects must fit into one of the strata categories listed in section 10.5 to be eligible to enroll on Part B of this study.

  14. Pre-enrollment tumor survey:

    Prior to enrollment on Part B, a determination of mandatory disease staging must be performed. Tumor imaging studies including CT or MRI, MIBG or PET, and VMA/HVA (PET scan should be done for patients with prior disease that was MIBG non-avid). Bone marrow aspirates and biopsies are required.

    This disease assessment is required for eligibility and should be done preferably within 2 weeks, but must be done within a maximum of 4 weeks before first dose of study drug.

  15. Timing- Enrollment to occur prior to Day + 120 post-transplant, preferably when the subject is within 28 days after completing local radiation therapy (if given).

Exclusion Criteria (Part A and B)

  1. Subjects who are 12-18 months of age with INSS Stage 4 and all stage 3 subjects with favorable biologic features (ie, nonamplified MYCN, favorable pathology, and DNA index > 1) are not eligible.
  2. Lactating females are not eligible unless they have agreed not to breastfeed their infants.
  3. Subjects receiving any investigational drug concurrently.
  4. Subjects with any other medical condition, including but not limited to 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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Standard Immunotherapy without DFMO
One of the following drugs will be chosen for each subject based on molecular guided results: ceritinib, dasatinib, sorafenib or vorinostat. This will be followed standard immunotherapy with Dinutuximab/GM-CSF/IL-2 and isotretinoin. At the end of immunotherapy, DFMO will be given to all subjects BID for 730 days.
Drug: Ceritinib
One of the following drugs will be chosen for each subject based on molecular guided results: Ceritinib, dasatinib, sorafenib or vorinostat. This will be followed by consolidation, immunotherapy +/- DFMO, and then all subjects will receive DFMO for 2 years as maintenance.
Other Names:
  • Zykadia
Drug: dasatinib
One of the following drugs will be chosen for each subject based on molecular guided results: Ceritinib, dasatinib, sorafenib or vorinostat. This will be followed by consolidation, immunotherapy +/- DFMO, and then all subjects will receive DFMO for 2 years as maintenance.
Other Names:
  • Sprycel
Drug: sorafenib
One of the following drugs will be chosen for each subject based on molecular guided results: Ceritinib, dasatinib, sorafenib or vorinostat. This will be followed by consolidation, immunotherapy +/- DFMO, and then all subjects will receive DFMO for 2 years as maintenance.
Other Names:
  • Nexavar
Drug: vorinostat
One of the following drugs will be chosen for each subject based on molecular guided results: Ceritinib, dasatinib, sorafenib or vorinostat. This will be followed by consolidation, immunotherapy +/- DFMO, and then all subjects will receive DFMO for 2 years as maintenance.
Other Names:
  • ZOLINZA
Active Comparator: Standard Immunotherapy with DFMO
One of the following drugs will be chosen for each subject based on molecular guided results: ceritinib, dasatinib, sorafenib or vorinostat. This will be followed standard immunotherapy with Dinutuximab/GM-CSF/IL-2 and isotretinoin PLUS 1000mg/m2 BID of DFMO. At the end of immunotherapy, all subjects will go on to receive DFMO BID for 730 days.
Drug: Ceritinib
One of the following drugs will be chosen for each subject based on molecular guided results: Ceritinib, dasatinib, sorafenib or vorinostat. This will be followed by consolidation, immunotherapy +/- DFMO, and then all subjects will receive DFMO for 2 years as maintenance.
Other Names:
  • Zykadia
Drug: dasatinib
One of the following drugs will be chosen for each subject based on molecular guided results: Ceritinib, dasatinib, sorafenib or vorinostat. This will be followed by consolidation, immunotherapy +/- DFMO, and then all subjects will receive DFMO for 2 years as maintenance.
Other Names:
  • Sprycel
Drug: sorafenib
One of the following drugs will be chosen for each subject based on molecular guided results: Ceritinib, dasatinib, sorafenib or vorinostat. This will be followed by consolidation, immunotherapy +/- DFMO, and then all subjects will receive DFMO for 2 years as maintenance.
Other Names:
  • Nexavar
Drug: vorinostat
One of the following drugs will be chosen for each subject based on molecular guided results: Ceritinib, dasatinib, sorafenib or vorinostat. This will be followed by consolidation, immunotherapy +/- DFMO, and then all subjects will receive DFMO for 2 years as maintenance.
Other Names:
  • ZOLINZA
Drug: DFMO
DFMO will be given to Arm B during immunotherapy and then for 2 years as maintenance to all subjects completing immunotherapy.
Other Names:
  • Eflornithine, α-difluoromethylornithine

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of days from start of therapy to date of first relapse
Time Frame: Up to 8 years

To measure the response of treatments chosen based on:

• Event free survival (EFS)
Up to 8 years
Number of subjects that have a targeted agent chosen for treatment.
Time Frame: 2 years

At completion of the induction therapy, the investigators will determine feasibility of adding molecularly guided targeted therapy to standard of care chemotherapy. Feasibility will be defined as:

  1. Subject has a targeted agent identified
  2. Receives 75% of dosing of medications while on study protocol during cycles 3-6
  3. Subject is not removed from study due to targeted agent drug related toxicity.
2 years
Number of subjects that receive 75% of dosing of medications while on study protocol during cycles 3-6.
Time Frame: 2 years

At completion of the induction therapy, the investigators will determine feasibility of adding molecularly guided targeted therapy to standard of care chemotherapy. Feasibility will be defined as:

  1. Subject has a targeted agent identified
  2. Receives 75% of dosing of medications while on study protocol during cycles 3-6
  3. Subject is not removed from study due to targeted agent drug related toxicity.
2 years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of days that subjects remain alive
Time Frame: 3 years plus 5 years follow up

To measure the response of treatments chosen based on:

  • Overall response rate (ORR) after induction therapy
  • Overall survival (OS)
3 years plus 5 years follow up
Overall Response Rate (ORR) of Participants by the presence of radiologically assessable disease by cross-sectional CT or MRI imaging and/or by MIBG or PET scans.
Time Frame: Up to 8 years

To measure the response of treatments chosen based on:

• Overall response rate (ORR) after induction therapy
Up to 8 years
Number of participants with treatment-related adverse events as assessed by CTCAE v4.0
Time Frame: 3 years
To compare toxicity effects of difluoromethylornithine (DFMO) in combination with Dinutuximab/GM-CSF/IL-2 and isotretinoin versus Dinutuximab/GM-CSF/IL-2 and isotretinoin alone.
3 years
Amount of pain medicine required by Arm A versus Arm B
Time Frame: 3 years
To compare level of pain medicine needed during immunotherapy in patients receiving difluoromethylornithine (DFMO) in combination with Dinutuximab/GM-CSF/IL-2 and Isotretinoin versus those receiving Dinutuximab/GM-CSF/IL-2 and isotretinoin alone.
3 years
Number of subjects required to go off therapy due to treatment-related adverse events as assessed by CTCAE v4.0.
Time Frame: 1 year

At completion of the induction therapy, the investigators will determine feasibility of adding molecularly guided targeted therapy to standard of care chemotherapy. Feasibility will be defined as:

  1. Subject has a targeted agent identified
  2. Receives 75% of dosing of medications while on study protocol during cycles 3-6
  3. Subject is not removed from study due to targeted agent drug related toxicity.
1 year

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Giselle Sholler

Collaborators

Beat NB Cancer Foundation
K C Pharmaceuticals Inc.
Team Parker for Life
Dell, Inc.

Investigators

  • Study Chair: Giselle Sholler, MD, Beat Childhood Cancer

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

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 Major Dates

Study Start (Actual)

September 1, 2015

Primary Completion (Estimated)

September 1, 2030

Study Completion (Estimated)

September 1, 2035

Study Registration Dates

First Submitted

September 22, 2015

First Submitted That Met QC Criteria

September 23, 2015

First Posted (Estimated)

September 24, 2015

Study Record Updates

Last Update Posted (Actual)

April 28, 2026

Last Update Submitted That Met QC Criteria

April 24, 2026

Last Verified

April 1, 2026

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • NMTRC012

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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