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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT02139397
Recruitment Status : Active, not recruiting
First Posted : May 15, 2014
Last Update Posted : April 28, 2022
Beat NB Cancer Foundation
Because of Ezra
K C Pharmaceuticals Inc.
Information provided by (Responsible Party):
Wake Forest University Health Sciences

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.

Condition or disease Intervention/treatment Phase
Neuroblastoma Recurrent Drug: DFMO Drug: Bortezomib Phase 1 Phase 2

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 16 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase I/II Trial of DFMO in Combination With Bortezomib in Patients With Relapsed or Refractory Neuroblastoma
Actual Study Start Date : May 2014
Estimated Primary Completion Date : December 2022
Estimated Study Completion Date : December 2023

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Neuroblastoma
Drug Information available for: Bortezomib

Arm Intervention/treatment
Experimental: DFMO and Bortezomib
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
Other Names:
  • D,L-ɑdifluoromethylornithine
  • Eflornithine

Drug: Bortezomib
Other Name: Velcade

Primary Outcome Measures :
  1. Number of Participants with Adverse Events as a Measure of Safety and Tolerability [ Time Frame: 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.

  2. Determine the Overall Response Rate (ORR) of Participants using RECIST criteria [ Time Frame: 3 years ]
    To determine the overall response rate (ORR) by the presence of radiologically assessable disease by cross-sectional imaging and in MIBG or PET scans.

Secondary Outcome Measures :
  1. Number of Participants with Adverse Events as a Measure of Safety and Tolerability [ Time Frame: 3 years ]
    Phase II- To continue to determine the safety and tolerability of DFMO in combination with bortezomib in subjects with relapsed or refractory neuroblastoma.

  2. Determine the Progression Free Survival (PFS) of Participants using days until progression [ Time Frame: 3 years ]

    To evaluate the activity of DFMO in combination with bortezomib based on:

    - Progression free survival (PFS)

  3. Correlate PET scan changes with Progression Free Survival [ Time Frame: 3 years ]
    For subjects followed with PET scan: comparison of changes in PET activity and correlation with PFS

  4. Biology studies [ Time Frame: 3 years ]
    Urine, blood, bone marrow and tumor biological Correlates will be explored. Dose effect of DFMO on biological correlates will also be explored.

  5. Correlate urinary polyamine levels with response and progression of disease in neuroblastoma. [ Time Frame: 3 years ]
    Correlation of urinary polyamine levels with response and progression of disease in neuroblastoma.

Information from the National Library of Medicine

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Ages Eligible for Study:   up to 21 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • 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 MIBG or 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:

    1. Subjects must have adequate liver function as defined by:

      • AST and ALT <5x upper limit of normal
      • Serum bilirubin must be ≤ 2.0 mg/dl
    2. 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 RBC 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.

Exclusion Criteria:

  • Lansky score <50%
  • BSA (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:

    1. Myelosuppressive chemotherapy: Must not have received within 2 weeks of enrollment onto this study (6 weeks if prior nitrosourea).
    2. Hematopoietic growth factors: At least 5 days since the completion of therapy with a growth factor.
    3. 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.
    4. Immunotherapy: At least 6 weeks since the completion of any type of immunotherapy, e.g. tumor vaccines.
    5. Monoclonal antibodies: At least 7 days or 3 half-lives, whichever is longer, must have elapsed since prior treatment with a monoclonal antibody.
    6. XRT: At least 14 days since the last treatment except for radiation delivered with palliative intent to a non-target site.
    7. 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02139397

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United States, Arkansas
Arkansas Children's Hospital
Little Rock, Arkansas, United States, 72202
United States, Connecticut
Connecticut Children's Hospital
Hartford, Connecticut, United States, 06106
United States, Florida
Arnold Palmer Hospital for Children- MD Anderson
Orlando, Florida, United States, 32806
United States, Michigan
Helen DeVos Children's Hospital
Grand Rapids, Michigan, United States, 49503
United States, Missouri
Children's Mercy Hospitals and Clinics
Kansas City, Missouri, United States, 64108
United States, South Carolina
Medical University of South Carolina
Charleston, South Carolina, United States, 29425
Sponsors and Collaborators
Wake Forest University Health Sciences
Beat NB Cancer Foundation
Because of Ezra
K C Pharmaceuticals Inc.
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Study Chair: Kathleen Neville, MD Children's Mercy Hospital Kansas City
Additional Information:
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Responsible Party: Wake Forest University Health Sciences
ClinicalTrials.gov Identifier: NCT02139397    
Other Study ID Numbers: NMTRC010
First Posted: May 15, 2014    Key Record Dates
Last Update Posted: April 28, 2022
Last Verified: February 2022
Additional relevant MeSH terms:
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Neuroectodermal Tumors, Primitive, Peripheral
Neuroectodermal Tumors, Primitive
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Antineoplastic Agents
Trypanocidal Agents
Antiprotozoal Agents
Antiparasitic Agents
Anti-Infective Agents
Ornithine Decarboxylase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action