NeuroblastomaPhase 2NCT04301843
Eflornithine (DFMO) and Etoposide for Relapsed/Refractory Neuroblastoma
A Phase 2 study testing Eflornithine in people with Neuroblastoma, run by Giselle Sholler at 29 sites in 2 countries.
Trial summary
Difluoromethylornithine (DFMO) will be used in an open label, multicenter, study in combination with etoposide for subjects with relapsed/refractory neuroblastoma. Read more about this study
- Who is it for?
- Ages Up to 31 years
- Conditions the study is for
- Neuroblastoma
- What is being tested?
- Eflornithine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 131 participants
- Where
- 29 sitesin 2 countries
- Study dates
- 25 Sep 2020to 1 Oct 2033
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Up to 31 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- All patients must have a pathologically confirmed diagnosis of neuroblastoma, ≤ 30.99 years of age with history of relapsed/refractory neuroblastoma.
- All patients must have completed upfront therapy with at least 4 cycles of aggressive multi-drug chemotherapy.
- Specific Criteria by Arm:
- Arms 1 and 2:
- Subjects with no active disease:
- No evidence of residual disease by CT/MRI and MIBG scan (or PET for patients who have a history of MIBG non-avid disease).
Show all 33Show fewer
- o Note: Patients with residual masses detected by CT/MRI may be considered in CR if their MIBG is negative or if MIBG positive and evaluated by PET and found to have negative PET scans; biopsy confirmation may be considered if there is still reasonable concern for persistent disease but is not required.
- No evidence of disease metastatic to bone marrow.
- Arm 3 [CLOSED TO ENROLLMENT]:
- Measurable or evaluable disease, including at least one of the following:
- Measurable tumor by CT or MRI; or a positive MIBG and PET; or positive bone marrow biopsy/aspirate in at least one site.
- Timing from prior therapy: Enrollment (first dose of DFMO) no later than 60 days from last dose of the most recent therapy.
- Subjects must have fully recovered from the acute toxic effects of all prior anti- cancer chemotherapy and be within the following timelines:
- Myelosuppressive chemotherapy: Must not have received within 2 weeks of enrollment onto this study (6 weeks if prior nitrosourea).
- Hematopoietic growth factors: At least 5 days since the completion of therapy with a growth factor.
- Biologic (anti-neoplastic agent): At least 7 days since the completion of therapy with a biologic agent. For agents that have known adverse events occurring beyond 7 days after administration, this period must be extended beyond the time during which adverse events are known to occur. The duration of this interval must be discussed with the Study Chair.
- Immunotherapy: At least 6 weeks since the completion of any type of immunotherapy, e.g. tumor vaccines, CAR-T cells.
- Anti-GD2 Monoclonal antibodies: At least 2 weeks must have elapsed since prior treatment with a monoclonal antibody.
- XRT: At least 14 days since the last treatment except for radiation delivered with palliative intent to a non-target site.
- Stem Cell Transplant:
- Allogeneic: No evidence of active graft vs. host disease
- Allo/Auto: ≥ 2 months must have elapsed since transplant.
- MIBG Therapy: At least 8 weeks since treatment with MIBG therapy
- Subjects must have a Lansky or Karnofsky Performance Scale score of 60% or higher.
- Life expectancy > 2 months
- All clinical and laboratory studies for organ functions to determine eligibility must be performed within 7 days prior to first dose of study drug unless otherwise indicated below.
- Subjects must have adequate organ functions at the time of registration:
- Hematological: Total absolute neutrophil count ANC ≥750/μL
- Liver: Subjects must have adequate liver function as defined by AST and ALT <5x upper limit of normal (Normal=45), Bilirubin <1.5x upper limit normal (Normal=1.0). Normal PT, PTT, fibrinogen.
- Renal: Estimated Glomerular Filtration rate (eGFR) as calculated from the Bedside Schwartz equation (in units of mL/min/1.73 m2) or via radioisotope GFR of ≥ 70.
- The Bedside Schwartz equation is: [(0.413) X (Height in cm)] / SCr
- Subjects of childbearing potential must have a negative pregnancy test. Subjects of childbearing potential must agree to use an effective birth control method. Subjects who are lactating must agree to stop breast-feeding.
- Written informed consent in accordance with institutional and FDA guidelines must be obtained from all subjects (or patients' legal representative).
Who cannot join
- BSA of <0.25 m2.
- Subjects that received DFMO at a dose higher than 1000mg/m2 BID prior to this study are not eligible.
- Subjects that received a dose of DFMO in combination with etoposide are not eligible.
- Investigational Drugs: Subjects who are currently receiving another investigational drug are excluded from participation.
- Anti-cancer Agents: Subjects who are currently receiving other anticancer agents are not eligible. Subjects must have fully recovered from hematological and bone marrow suppression effects of prior chemotherapy.
- Infection: Subjects who have an uncontrolled infection are not eligible until the infection is judged to be well controlled in the opinion of the investigator.
- Subjects who, in the opinion of the investigator, may not be able to comply with the safety monitoring requirements of the study, or in whom compliance is likely to be suboptimal, should be excluded.
Trial locations and contacts
29 sites in 2 countries.
29 sites in 2 countries
United States24 sites
Augusta University Health
Augusta, Georgia, 30912
Dell Children's Blood and Cancer Center
Austin, Texas, 78723
University of Alabama/Children's of Alabama
Birmingham, Alabama, 35201
Medical University of South Carolina
Charleston, South Carolina, 29425
Levine Children's Hospital
Charlotte, North Carolina, 28204
Cleveland Clinic Children's
Cleveland, Ohio, 44195
Children's Medical Center Dallas
Dallas, Texas, 75235
Helen DeVos Children's Hospital
Grand Rapids, Michigan, 49503
Hackensack University Medical Center
Hackensack, New Jersey, 07601
Connecticut Children's Hospital
Hartford, Connecticut, 06106
Penn State Milton S. Hershey Medical Center and Children's Hospital
Hershey, Pennsylvania, 17033
University of Iowa
Iowa City, Iowa, 52242
Children's Mercy Hospitals and Clinics
Kansas City, Missouri, 64108
Arkansas Children's Hospital
Little Rock, Arkansas, 72202
Norton Children's Research Institute/Affiliated with University of Louisville School of Medicine
Louisville, Kentucky, 40201
Medical College of Wisconsin
Milwaukee, Wisconsin, 53226
Children's Hospital and Clinics of Minnesota
Minneapolis, Minnesota, 55404
Children's Hospital of The King's Daughters
Norfolk, Virginia, 23507
UCSF Benioff Children's Hospital Oakland
Oakland, California, 94609
Arnold Palmer Hospital for Children
Orlando, Florida, 32806
Hasbro Children's Hospital
Providence, Rhode Island, 02901
Rady Children's Hospital
San Diego, California, 92123
Cardinal Glennon Children's Hospital
St Louis, Missouri, 63104
St. Joseph's Children's Hospital
Tampa, Florida, 33614
Canada5 sites
Alberta Children's Hospital
Calgary, Alberta, AB T3B 6A8
UHC Sainte-Justine
Montreal, Quebec, QC H3S 2G4
Montreal Children's Hospital
Montreal, Quebec, QC H4A 3H9
CHUQ
Québec, Quebec, QC G1V 4W6
CancerCare Manitoba
Winnipeg, Manitoba, MB R3E 0V9
About this study
Official title: Phase II Trial of Eflornithine (DFMO) and Etoposide for Relapsed/Refractory Neuroblastoma
Difluoromethylornithine (DFMO) will be used in an open label, multicenter, study in combination with etoposide for subjects with relapsed/refractory neuroblastoma.
Read the detailed description
Difluoromethylornithine (DFMO) will be used in an open label, multicenter, study in combination with etoposide for subjects with relapsed/refractory neuroblastoma.
In this study subjects will receive six 21-day cycles of Etoposide and DFMO followed by an additional 630 days of DFMO alone.
Subjects will be evaluated in 3 arms:
- Arm 1: Subjects who show no active disease after receiving any additional therapy for neuroblastoma that was refractory to standard induction/consolidation therapy.
Refractory: Subjects with progressive disease on upfront therapy OR did not have at least PR on induction OR required additional second line therapy to achieve remission who are now in first remission.
- Arm 2: Subjects who have previously relapsed and currently show no active disease (in CR2 or greater).
- Arm 3: Subjects who are relapsed or refractory with active disease.- CLOSED TO ENROLLMENT
- Conditions
- Neuroblastoma
- Being tested
- Eflornithine
- Medical subject headings
- Neuroblastoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
EflornithineDrug
Also called DFMO, difluoromethylornithine
DFMO (difluoromethylornithine) will be given at a dose of 1000 mg/m2 BID on each day of study.
| Study group | Role | What they receive |
|---|---|---|
| Eflornithine (DFMO) | Experimental | In this study subjects will receive six 21-day cycles of Etoposide and DFMO followed by an additional 630 days of DFMO alone.
Etoposide will be given at 50 mg/m2/dose PO daily for the first 14 days of each 21 days until 6 cycles of etoposide are completed.
DFMO (difluoromethylornithine) will be given at a dose of 1000 mg/m2 BID on each day of study. Receives: Drug: Eflornithine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of participants with event free survival (EFS) during study
To evaluate the efficacy of difluoromethylornithine (DFMO) in combination with etoposide in patients with relapsed/refractory neuroblastoma, based upon:
- Event free survival (EFS) from time of enrollment.
Measured: 2 years plus 5 years follow up
Secondary outcomes (3)
Length of time that participants experience Overall Survival (OS)
To evaluate the efficacy of difluoromethylornithine (DFMO) in combination with etoposide in patients with relapsed/refractory neuroblastoma, based upon:
- Overall Survival (OS) from time of enrollment.
Measured: 7 years
Determine the Overall Response Rate (ORR) of Participants using INSS Response Evaluation Criteria.
To evaluate the efficacy of difluoromethylornithine (DFMO) in combination with etoposide in patients with relapsed/refractory neuroblastoma, based upon:
- Response Rate for patients with active disease (Arm 3) using International Neuroblastoma Staging System (INSS) Response Evaluation Criteria.
Measured: 2 years
Number of Participants with Adverse Events as a Measure of Safety and Tolerability
To monitor the safety and tolerability profile of difluoromethylornithine (DFMO) in combination with etoposide in pediatric and young adult patients with relapsed/refractory neuroblastoma.
Measured: 2 years plus 30 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Mar 2020
- Study start25 Sep 2020
- Primary completion1 Oct 2028 (estimated)
- Study completion1 Oct 2033 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for NeuroblastomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 131 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Giselle Sholler
- Sponsor type
- University, hospital or other
- Collaborators
- K C Pharmaceuticals Inc., Beat NB Cancer Foundation, Team Parker for Life, USWM, LLC
- Responsible party
- Sponsor-investigator, Giselle Sholler, Milton S. Hershey Medical Center
- Investigators
- Giselle Sholler, MD, Study chair, Beat Childhood Cancer
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04301843
- Sponsor's protocol ID
- BCC015
- Status last verified
- Sep 2026
- First submitted
- 6 Mar 2020
- Last updated
- 3 Sep 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
- Expanded access
- Available
Study at a glance
From the registry record, last updated by the sponsor on 3 Sep 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase II Trial of Eflornithine (DFMO) and Etoposide for Relapsed/Refractory Neuroblastoma
- ClinicalTrials.gov ID
- NCT04301843
- Acronym / sponsor ID
- BCC015
- Conditions
- Neuroblastoma
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 131 participants (estimated)
- Lead sponsor
- Giselle ShollerUniversity, hospital or other
- Collaborators
- K C Pharmaceuticals Inc., Beat NB Cancer Foundation, Team Parker for Life, USWM, LLC
- Study start
- 25 Sep 2020 (actual)
- Primary completion
- 1 Oct 2028 (estimated)
- Study completion
- 1 Oct 2033 (estimated)
- First posted
- 10 Mar 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Difluoromethylornithine (DFMO) will be used in an open label, multicenter, study in combination with etoposide for subjects with relapsed/refractory neuroblastoma.
Detailed description
Difluoromethylornithine (DFMO) will be used in an open label, multicenter, study in combination with etoposide for subjects with relapsed/refractory neuroblastoma.
In this study subjects will receive six 21-day cycles of Etoposide and DFMO followed by an additional 630 days of DFMO alone.
Subjects will be evaluated in 3 arms:
- Arm 1: Subjects who show no active disease after receiving any additional therapy for neuroblastoma that was refractory to standard induction/consolidation therapy.
Refractory: Subjects with progressive disease on upfront therapy OR did not have at least PR on induction OR required additional second line therapy to achieve remission who are now in first remission.
- Arm 2: Subjects who have previously relapsed and currently show no active disease (in CR2 or greater).
- Arm 3: Subjects who are relapsed or refractory with active disease.- CLOSED TO ENROLLMENT
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Eflornithine (DFMO) | Experimental | Drug: EflornithineIn this study subjects will receive six 21-day cycles of Etoposide and DFMO followed by an additional 630 days of DFMO alone. Etoposide will be given at 50 mg/m2/dose PO daily for the first 14 days of each 21 days until 6 cycles of etoposide are completed. DFMO (difluoromethylornithine) will be given at a dose of 1000 mg/m2 BID on each day of study. |
Who may qualify
- Ages
- Up to 31 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (33 listed)
- All patients must have a pathologically confirmed diagnosis of neuroblastoma, ≤ 30.99 years of age with history of relapsed/refractory neuroblastoma.
- All patients must have completed upfront therapy with at least 4 cycles of aggressive multi-drug chemotherapy.
- Specific Criteria by Arm:
- No evidence of residual disease by CT/MRI and MIBG scan (or PET for patients who have a history of MIBG non-avid disease).
- o Note: Patients with residual masses detected by CT/MRI may be considered in CR if their MIBG is negative or if MIBG positive and evaluated by PET and found to have negative PET scans; biopsy confirmation may be considered if there is still reasonable concern for persistent disease but is not required.
Key exclusion criteria (7 listed)
- BSA of <0.25 m2.
- Subjects that received DFMO at a dose higher than 1000mg/m2 BID prior to this study are not eligible.
- Subjects that received a dose of DFMO in combination with etoposide are not eligible.
- Investigational Drugs: Subjects who are currently receiving another investigational drug are excluded from participation.
- Anti-cancer Agents: Subjects who are currently receiving other anticancer agents are not eligible. Subjects must have fully recovered from hematological and bone marrow suppression effects of prior chemotherapy.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| EflornithineAlso: DFMO, difluoromethylornithineDFMO (difluoromethylornithine) will be given at a dose of 1000 mg/m2 BID on each day of study. | Drug | Eflornithine (DFMO) |
Primary outcome
Number of participants with event free survival (EFS) during study
Time frame: 2 years plus 5 years follow up
To evaluate the efficacy of difluoromethylornithine (DFMO) in combination with etoposide in patients with relapsed/refractory neuroblastoma, based upon: o Event free survival (EFS) from time of enrollment.
3 secondary outcomes
Length of time that participants experience Overall Survival (OS)
Time frame: 7 years
Determine the Overall Response Rate (ORR) of Participants using INSS Response Evaluation Criteria.
Time frame: 2 years
Number of Participants with Adverse Events as a Measure of Safety and Tolerability
Time frame: 2 years plus 30 days
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Sep 2026.
- Beat Childhood Cancer Consortium websiteLink provided by the sponsor.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Giselle Sholler, MD study chair
Beat Childhood Cancer
29 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Eflornithine in people with Neuroblastoma, run by Giselle Sholler at 29 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 33 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 3 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 29 sites in United States, Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of participants with event free survival (EFS) during study (time frame: 2 years plus 5 years follow up). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Sep 2026.