Neuroblastoma RecurrentPhase 1/2NCT02139397

Study of Difluoromethylornithine (DFMO) in Combination With Bortezomib for Relapsed or Refractory Neuroblastoma

A Phase 1/2 study testing DFMO and Bortezomib in people with Neuroblastoma Recurrent, run by Giselle Sholler at 6 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

The purpose of this research study is to evaluate an investigational drug (DFMO) in combination with bortezomib, for relapsed and refractory neuroblastoma. DFMO is an investigational drug because it has not been approved by the U.S. Food and Drug Administration (FDA). Read more about this study

Who is it for?: Ages Up to 21 years
Conditions the study is for: Neuroblastoma Recurrent
What is being tested?: DFMO and Bortezomib
Type of treatment: Pill or oral medicine, Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 16 participants
Where: 6 sitesUnited States
Study dates: 6 Jun 2014to 19 Jan 2024
Phase: Phase 1/2
Are there results?: Yes, posted in the registrySummary in the doctors' view

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 21 years
All sexes
No healthy volunteers
Child, Adult

Who may be able to join

Age: ≤ 21 years at the time of diagnosis.
Diagnosis: Histologic verification at either the time of original diagnosis or relapse of neuroblastoma.
Disease Status: For the purposes of this study, aggressive multidrug chemotherapy is defined as chemotherapy including 2 or more agents that must include an alkylating agent and a platinum-containing compound. Patients must have one of the following:
First episode of recurrent disease following completion of aggressive multi-drug frontline therapy.
First episode of progressive disease during aggressive multi-drug frontline therapy.
Primary resistant/refractory disease detected at the conclusion of at least 4 cycles of aggressive multidrug induction chemotherapy on or according to a high-risk neuroblastoma protocol (examples include Children's Oncology Group trials: A3973, ANBL0532, ANBL09P1, etc.).

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Measurable or evaluable disease, including at least one of the following: Measureable tumor by CT or MRI; or A positive meta-iodobenzylguanidine (MIBG) or positron emission computed tomography (PET) scan; or Positive bone marrow biopsy/aspirate.
Current disease state must be one for which there is currently no known curative therapy or no additional therapies proven to prolong survival with an acceptable quality of life.
A negative urine pregnancy test is required for female subjects of child bearing potential (onset of menses or ≥13 years of age).
Organ Function Requirements:
Subjects must have adequate liver function as defined by:
AST (aspartate aminotransferase) and alanine aminotransferase (ALT) <5x upper limit of normal
Serum bilirubin must be ≤ 2.0 mg/dl
Subjects must have adequate Bone Marrow function defined as:
For patients without bone marrow involvement:
Peripheral absolute neutrophil count (ANC) ≤ 750/uL
Platelet count 50,000/uL (transfusion independent, defined as not receiving platelet transfusions within a 7 day period prior to enrollment. Exception: Patients that are platelet dependent due to previous extensive treatment- e.g. - MIBG therapy).
Hemoglobin ≥ 8.0 g/dL (may receive red blood cell transfusions) Patients known to have bone marrow involvement with neuroblastoma are eligible provided that minimum ANC and platelet count criteria are met but are not evaluable for hematological toxicity.
Subjects must have adequate renal function defined as: Serum creatinine based on age/gender.
Informed Consent: All subjects and/or legal guardians must sign informed written consent. Assent, when appropriate, will be obtained according to institutional guidelines.

Who cannot join

Lansky score <50%
BSA (body surface area) body surface body surface m2 of <0.25
Prior Therapy- Patients 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.

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Immunotherapy: At least 6 weeks since the completion of any type of immunotherapy, e.g. tumor vaccines.
Monoclonal antibodies: At least 7 days or 3 half-lives, whichever is longer, must have elapsed since prior treatment with a monoclonal antibody.
Radiotherapy: At least 14 days since the last treatment except for radiation delivered with palliative intent to a non-target site.
Stem Cell Transplant or Rescue: No evidence of active graft vs. host disease and ≥ 2 months must have elapsed since transplant.
Investigational Drugs: Subjects who have received another investigational drug within the last 14 days are excluded from participation.
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

6 sites in 1 country.

City, postcode or hospital

6 sites in 1 country

United States6 sites

Medical University of South Carolina
Charleston, South Carolina, 29425
Helen DeVos Children's Hospital
Grand Rapids, Michigan, 49503
Connecticut Children's Hospital
Hartford, Connecticut, 06106
Children's Mercy Hospitals and Clinics
Kansas City, Missouri, 64108
Arkansas Children's Hospital
Little Rock, Arkansas, 72202
Arnold Palmer Hospital for Children- MD Anderson
Orlando, Florida, 32806

Other trials in United States

About this study

Official title: A Phase I/II Trial of DFMO in Combination With Bortezomib in Patients With Relapsed or Refractory Neuroblastoma

Conditions: Neuroblastoma Recurrent
Being tested: DFMO, Bortezomib

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

DFMODrug
Also called D,L-ɑdifluoromethylornithine, Eflornithine
BortezomibDrug
Also called Velcade

Study groups in NCT02139397
Study group	Role	What they receive
DFMO and Bortezomib	Experimental	Subjects will take DFMO by mouth 2 times a day for each day of a 21 day cycle and Bortezomib will be given by IV push on days 1, 4, and 8 of each 21 day cycle. Receives: Drug: DFMO; Drug: Bortezomib

What is being measured

The primary outcome is the main question the study is designed to answer.

Number of Participants With Adverse Events as a Measure of Safety and Tolerability
Phase I- To determine the safety and tolerability of DFMO in combination with bortezomib at 3 dose levels of DFMO: 1500mg/m2 twice daily, 2000mg/m2 twice daily, and 2500mg/m2 twice daily in subjects with relapsed or refractory neuroblastoma who receive one full cycle of this dose.
Phase II- Study did not enroll to Phase II. Study completed at end of Phase I.
Measured: Adverse Events were collected starting with the date of the first dose of study drug until 30 days after last dose of study drug, ongoing related adverse events were continued to be followed until resolution, on average 6 months.

Secondary outcomes (2)

Determine the Overall Response Rate (ORR) of Participants Using RECIST Criteria
To determine the overall response rate (ORR) by the presence of radiologically assessable disease by cross-sectional imaging and in MIBG (meta-iodobenzylguanidine) or PET (positron emission computed tomography) scans. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by CT or MRI imaging and/or by MIBG or PET scans: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Progressive Disease (PD), At least a 20% increase in the sum of the disease measurements for measurable lesions, Stable Disease, Neither sufficient decrease to qualify for PR or sufficient increase to qualify for PD from study entry. Overall Response (OR) = CR + PR.
Measured: Followed until off therapy, generally 1 year
Determine the Progression Free Survival (PFS) of Participants Using Days Until Progression
Time to progression (PFS), defined as the period from the start of the treatment until the criteria for progression are met taking as reference the screening measurements. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), as at least a 20% increase in the sum of the disease measurements for measurable lesions, taking as reference the smallest disease measurement recorded since the start of treatment (nadir), and minimum 5 mm increase over the nadir or the appearance of one or more new lesions or appearance of positive bone marrow.
Measured: From date of start of treatment until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 1 year

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

6 Jun 201419 Jan 2024

First posted15 May 2014 (estimated)
Study start6 Jun 2014
Primary completion19 Jan 2024
Study completion19 Jan 2024

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Other trials for Neuroblastoma RecurrentStudies 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 1/2
Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Enrolment: 16 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT02139397
Sponsor's protocol ID: NMTRC010
Status last verified: Aug 2024
First submitted: 13 May 2014
Last updated: 6 Aug 2024
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

RecruitingPhase 1/2
Testing the Addition of Iberdomide to Therapy in People With Neuroblastoma That Has Come Back, Not Responded to Treatment, or Gotten Worse
Recurrent Ganglioneuroblastoma, Recurrent Neuroblastoma
Active, not recruitingPhase 2
Ensartinib in Treating Patients With Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin Lymphoma, or Histiocytic Disorders With ALK or ROS1 Genomic Alterations (A Pediatric MATCH Treatment Trial)
Advanced Malignant Solid Neoplasm, Malignant Solid Neoplasm
Active, not recruitingPhase 2
Erdafitinib in Treating Patients With Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin Lymphoma, or Histiocytic Disorders With FGFR Mutations (A Pediatric MATCH Treatment Trial)
Advanced Malignant Solid Neoplasm, Recurrent Childhood Ependymoma
Active, not recruitingPhase 2
Tipifarnib for the Treatment of Advanced Solid Tumors, Lymphoma, or Histiocytic Disorders With HRAS Gene Alterations, a Pediatric MATCH Treatment Trial
Malignant Solid Neoplasm, Recurrent Adrenal Gland Pheochromocytoma
Active, not recruitingPhase 2
Selpercatinib for the Treatment of Advanced Solid Tumors, Lymphomas, or Histiocytic Disorders With Activating RET Gene Alterations, a Pediatric MATCH Treatment Trial
Hematopoietic and Lymphatic System Neoplasm, Recurrent Ependymoma

All Neuroblastoma Recurrent trials

Study at a glance

From the registry record, last updated by the sponsor on 6 Aug 2024. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Phase I/II Trial of DFMO in Combination With Bortezomib in Patients With Relapsed or Refractory Neuroblastoma
ClinicalTrials.gov ID: NCT02139397
Acronym / sponsor ID: NMTRC010
Conditions: Neuroblastoma Recurrent
Phase: Phase 1/2
Study type: Interventional
Recruitment status: Completed
Enrolment: 16 participants (actual)
Lead sponsor: Giselle ShollerUniversity, hospital or other
Collaborators: Beat NB Cancer Foundation, Because of Ezra, K C Pharmaceuticals Inc.
Study start: 6 Jun 2014 (actual)
Primary completion: 19 Jan 2024 (actual)
Study completion: 19 Jan 2024 (actual)
First posted: 15 May 2014 (estimated)
Results: Posted 25 Apr 2024

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Study design

Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Number of arms: 1

Arm	Type	Receives
DFMO and Bortezomib	Experimental	Drug: DFMO, Drug: BortezomibSubjects will take DFMO by mouth 2 times a day for each day of a 21 day cycle and Bortezomib will be given by IV push on days 1, 4, and 8 of each 21 day cycle.

Who may qualify

Ages: Up to 21 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Child, Adult

Key inclusion criteria (20 listed)

Age: ≤ 21 years at the time of diagnosis.
Diagnosis: Histologic verification at either the time of original diagnosis or relapse of neuroblastoma.
Disease Status: For the purposes of this study, aggressive multidrug chemotherapy is defined as chemotherapy including 2 or more agents that must include an alkylating agent and a platinum-containing compound. Patients must have one of the following:
First episode of recurrent disease following completion of aggressive multi-drug frontline therapy.
First episode of progressive disease during aggressive multi-drug frontline therapy.

Key exclusion criteria (13 listed)

Lansky score <50%
BSA (body surface area) body surface body surface m2 of <0.25
Prior Therapy- Patients must have fully recovered from the acute toxic effects of all prior anti- cancer chemotherapy and be within the following timelines:
Investigational Drugs: Subjects who have received another investigational drug within the last 14 days are excluded from participation.
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.

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
DFMOAlso: D,L-ɑdifluoromethylornithine, Eflornithine	Drug	DFMO and Bortezomib
BortezomibAlso: Velcade	Drug	DFMO and Bortezomib

Primary outcome

Number of Participants With Adverse Events as a Measure of Safety and Tolerability
Time frame: Adverse Events were collected starting with the date of the first dose of study drug until 30 days after last dose of study drug, ongoing related adverse events were continued to be followed until resolution, on average 6 months.
Phase I- To determine the safety and tolerability of DFMO in combination with bortezomib at 3 dose levels of DFMO: 1500mg/m2 twice daily, 2000mg/m2 twice daily, and 2500mg/m2 twice daily in subjects with relapsed or refractory neuroblastoma who receive one full cycle of this dose. Phase II- Study did not enroll to Phase II. Study completed at end of Phase I.

2 secondary outcomes

Determine the Overall Response Rate (ORR) of Participants Using RECIST Criteria
Time frame: Followed until off therapy, generally 1 year
Determine the Progression Free Survival (PFS) of Participants Using Days Until Progression
Time frame: From date of start of treatment until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 1 year

Results and safety

Results posted to the registry on 25 Apr 2024, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Phase I: Difluoromethylornithine (DFMO) 1500 mg/m^2	3	3
Phase I: DFMO 2000 mg/m^2	7	7
Phase I: DFMO 2500 mg/m^2	6	6
Phase 2	0	0

Primary outcome: Number of Participants With Adverse Events as a Measure of Safety and Tolerability

Time frame: Adverse Events were collected starting with the date of the first dose of study drug until 30 days after last dose of study drug, ongoing related adverse events were continued to be followed until resolution, on average 6 months.. Count of participants. Unit: Participants

Measure	Phase I: DFMO 1500 mg/m^2 n = 3	Phase I: DFMO 2000 mg/m^2" n = 7	Phase I: DFMO 2500 mg/m^2" n = 6	Phase 2 n = 0
Value	2	1	3	–

Population analysed: All subjects that took at least one dose of DFMO

2 secondary outcomes are reported in the full results.

Adverse events

Time frame: Adverse Events were collected starting with the date of the first dose of study drug until 30 days after last dose of study drug, ongoing related adverse events were continued to be followed until resolution, on average of 1 year.. Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Phase I: DFMO 1500 mg/m^2	0 of 3 (0%)	2 of 3 (66.7%)	0 of 3
Phase I: DFMO 2000 mg/m^2	1 of 7 (14.3%)	1 of 7 (14.3%)	1 of 7
Phase I: DFMO 2500 mg/m^2	1 of 6 (16.7%)	3 of 6 (50%)	1 of 6

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 6 Aug 2024.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Beat Childhood Cancer Consortium websiteLink provided by the sponsor.

Related trials for Neuroblastoma Recurrent

RecruitingPhase 1/2
Testing the Addition of Iberdomide to Therapy in People With Neuroblastoma That Has Come Back, Not Responded to Treatment, or Gotten Worse
Recurrent Ganglioneuroblastoma, Recurrent Neuroblastoma
Active, not recruitingPhase 2
Ensartinib in Treating Patients With Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin Lymphoma, or Histiocytic Disorders With ALK or ROS1 Genomic Alterations (A Pediatric MATCH Treatment Trial)
Advanced Malignant Solid Neoplasm, Malignant Solid Neoplasm
Active, not recruitingPhase 2
Erdafitinib in Treating Patients With Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin Lymphoma, or Histiocytic Disorders With FGFR Mutations (A Pediatric MATCH Treatment Trial)
Advanced Malignant Solid Neoplasm, Recurrent Childhood Ependymoma
Active, not recruitingPhase 2
Tipifarnib for the Treatment of Advanced Solid Tumors, Lymphoma, or Histiocytic Disorders With HRAS Gene Alterations, a Pediatric MATCH Treatment Trial
Malignant Solid Neoplasm, Recurrent Adrenal Gland Pheochromocytoma
Active, not recruitingPhase 2
Selpercatinib for the Treatment of Advanced Solid Tumors, Lymphomas, or Histiocytic Disorders With Activating RET Gene Alterations, a Pediatric MATCH Treatment Trial
Hematopoietic and Lymphatic System Neoplasm, Recurrent Ependymoma

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.

Kathleen Neville, MD study chair

Children's Mercy Hospital Kansas City

6 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing DFMO and Bortezomib in people with Neuroblastoma Recurrent, run by Giselle Sholler at 6 sites in United States.

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 20 inclusion and 13 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: finished, as of the sponsor's last update on 6 Aug 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 6 sites in United States. 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 combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

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?

Yes. Results are posted in the registry (first posted 25 Apr 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

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 Adverse Events as a Measure of Safety and Tolerability (time frame: Adverse Events were collected starting with the date of the first dose of study drug until 30 days after last dose of study drug, ongoing related adverse events were continued to be followed until resolution, on average 6 months.). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02139397.

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 6 Aug 2024; AzTrials last refreshed its copy on 7 Nov 2026.