IRB Study Number 18-337
Status Recruiting
Phase Phase 2
Location Cleveland Clinic Main Campus
Institute Taussig Cancer Institute
Description
Primary Objective:
- To evaluate the efficacy of difluoromethylornithine (DFMO) as a single agent in preventing relapse in patients with high-risk neuroblastoma who are in remission, based upon:
- Event free survival (EFS) from time of enrollment.
Secondary Objectives:
- To evaluate the efficacy of difluoromethylornithine (DFMO) as a single agent in preventing relapse in patients with high-risk neuroblastoma who are in remission, based upon:
- Overall Survival (OS) from time of enrollment.
- EFS of the subset of patients with pre-immunotherapy Curie Scores >0.
- To develop a complete safety and tolerability profile of difluoromethylornithine (DFMO) as a single agent in pediatric and young adult patients with high risk neuroblastoma that is in remission.
- To further define the pharmacokinetics (PK) of DFMO in pediatric patients.
- Biological Correlates to minimally include:
- Blood: ODC SNP analysis in DNA isolated from nucleated cells, circulating DNA analysis, and explorative biomarker analysis.
Inclusion Criteria
- All patients must have a pathologically confirmed diagnosis of neuroblastoma, ≤ 30.99 years of age 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.
- All patients must be in complete remission (CR):
- No evidence of residual disease by CT/MRI and MIBG (or PET for patients who have a history of MIBG non-avid disease) scan.
- 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.
- Specific Criteria by Stratum:
- Stratum 1: All patients must have completed standard upfront therapy that replicates treatment which patients who were enrolled on ANBL0032 received, including:
- intensive induction chemotherapy and (if feasible) resection of primary tumor, followed by:
- consolidation with high-dose chemotherapy with ASCT and radiotherapy (see note below), followed by:
- Immunotherapy with Ch14.18/IL-2/GM-CSF (dinutuximab) and retinoic acid;
- Examples of such therapies include:
- Treatment as per A3973 protocol;
- Treatment as per POG 9341/9342 protocol;
- Treatment as per CCG3891;
- Enrollment on or following treatment as per ANBL02P1;
- Enrollment on or following treatment as per ANBL07P1.
- Tandem transplant patients are eligible if treated:
- On or as per ANBL0532;
- On or as per POG 9640;
- On or as per COG ANBL00P1; or,
- On or as CHP 594/DFCI 34-DAT.
- All subjects on Stratum 1 must have also met the following criteria:
- A pre-ASCT disease status evaluation that met International Neuroblastoma Response Criteria (INRC) for CR, VGPR, or PR for primary site, soft tissue metastases and bone metastases. Patients who meet those criteria must also meet the protocol-specified criteria for bone marrow response prior to ASCT as outlined below:
- No more than 10% tumor involvement (based on total nucleated cellular content) seen on any specimen from a bilateral bone marrow aspirate/biopsy.
- Because of potential sampling variation, patients who had a negative marrow at or following diagnosis, and then subsequently have a positive marrow-but with ≤ 10% tumor involvement-on any of the bilateral marrow aspirate/biopsy specimens done at or prior to pre-ASCT evaluation (which would be considered Progressive Disease by INRC), will still be considered eligible as long as the bone marrow is negative at the time of enrollment and there was no other evidence of progressive disease during upfront therapy.
- Note: Radiotherapy may be waived for patients who either have small adrenal masses which are completely resected at the time of diagnosis, or who never have an identifiable primary tumor. In this case please consult with Study Chairs to confirm eligibility.
- Stratum 2: Neuroblastoma that is in first complete remission following standard upfront therapy different from that described for Stratum 1.
- Stratum 3: Refractory Subjects- 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 that are now in first remission.
- Stratum 4: Subjects who have achieved a second or subsequent CR following relapse(s).
Exclusion Criteria
- BSA of <0.25 m2.
- 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.
