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

NCT02139397 | Completed Phase 1 Results DMC

• 1 other identifier: NMTRC010
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 6

Brief 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). This study will look at the safety and tolerability of DFMO in combination with bortezomib as well as the tumors response to this study drug.

Conditions

Neuroblastoma Recurrent

Outcome Measures

Primary Outcomes (1)

• 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.

  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

  Followed until off therapy, generally 1 year

• Determine the Progression Free Survival (PFS) of Participants Using Days Until Progression

  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

Study Arms (1)

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.

Drug: DFMO; Drug: Bortezomib

Interventions

DFMO DRUG

Also known as: D,L-ɑdifluoromethylornithine, Eflornithine

DFMO and Bortezomib

Bortezomib DRUG

Also known as: Velcade

DFMO and Bortezomib

Eligibility Criteria

• Age: Up to 21 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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.).
• 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:

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• Giselle Sholler: lead
• Beat NB Cancer Foundation: collaborator
• Because of Ezra: collaborator
• K C Pharmaceuticals Inc.: collaborator

Study Sites (6)

Arkansas Children's Hospital

Little Rock, Arkansas, 72202, United States

Location

Connecticut Children's Hospital

Hartford, Connecticut, 06106, United States

Location

Arnold Palmer Hospital for Children- MD Anderson

Orlando, Florida, 32806, United States

Location

Helen DeVos Children's Hospital

Grand Rapids, Michigan, 49503, United States

Location

Children's Mercy Hospitals and Clinics

Kansas City, Missouri, 64108, United States

Location

Medical University of South Carolina

Charleston, South Carolina, 29425, United States

Location

Related Links

• Beat Childhood Cancer Consortium website

MeSH Terms

Interventions

Eflornithine; Bortezomib

Intervention Hierarchy (Ancestors)

Ornithine; Amino Acids, Basic; Amino Acids; Amino Acids, Peptides, and Proteins; Amino Acids, Diamino; Boronic Acids; Acids, Noncarboxylic; Acids; Inorganic Chemicals; Boron Compounds; Organic Chemicals; Pyrazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Giselle Sholler, MD
• Organization: Beat Childhood Cancer

gsaulniersholler@pennstatehealth.psu.edu

7175310003

Study Officials

• Kathleen Neville, MD

  Children's Mercy Hospital Kansas City

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Beat Childhood Cancer Chair

Study Record Dates

• First Submitted: May 13, 2014
• First Posted: May 15, 2014
• Study Start: June 6, 2014
• Primary Completion: January 19, 2024
• Study Completion: January 19, 2024
• Last Updated: August 6, 2024
• Results First Posted: April 25, 2024

Record last verified: 2024-08

Locations

US (6)