NMTRC 014, NMTT- Neuroblastoma Maintenance Therapy Trial Using Difluoromethylornithine (DFMO)
Study ID: STU 022016-028
Difluoromethylornithine (DFMo) will be used in an open label, single agent, multicenter, study for patients with neuroblastoma in remission. in this study subjects will receive 730 Days of oral difluoromethylornithine (DFMo) at a dose of 500 to 1000 mg/m2 BiD on each day of study. * Stratum 1: Subjects who are in remission at the completion of standard upfront CoG induction, consolidation and maintenance therapy as defined in the inclusion criteria. This stratum will provide a prospective evaluation of a patient population that enrolled on the anBL0032 study. * Stratum 2: neuroblastoma that is in first complete remission following standard upfront therapy different from that described for Stratum 1. * Stratum 3: Subjects who are in first remission after receiving any additional therapy for neuroblastoma that was refractory to standard induction/consolidation therapy. Refractory: neuroblastoma that failed to have a response of at least PR following induction chemotherapy and surgical resection of the primary tumor, but that has achieved CR following additional therapy. * Stratum 4: Subjects who have achieved a second or subsequent CR following relapse(s). Subjects who receive 730 days of DFMo will be considered as having completed protocol therapy.
1. 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. 2. All patients must be in complete remission (CR): i. No evidence of residual disease by CT/MRI and MIBG scan o Note: Patients with residual masses detected by CT/MRI who have negative PET scans can be considered to be in CR; biopsy confirmation may be considered if there is still reasonable concern for persistent disease but is not required. ii. No evidence of disease metastatic to bone marrow. 3. 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: i. intensive induction chemotherapy and (if feasible) resection of primary tumor, followed by: ii. consolidation with high-dose chemotherapy with ASCT and radiotherapy (see note below), followed by: iii. immunotherapy with Ch14.18/IL-2/GM-CSF (dinutuximab) and retinoic acid; 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: o No more than 10% tumor involvement (based on total nucleated cellular content) seen on any specimen from a bilateral bone marrow aspirate/biopsy. o 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: Neuroblastoma that failed to have a response of at least PR following induction chemotherapy and surgical resection of the primary tumor, but that has achieved CR following additional therapy. Stratum 4: Patients who have achieved a second or subsequent CR following relapse(s). 4. Pre-enrollment tumor survey: Prior to enrollment on this study, a determination of mandatory disease staging must be performed: * Tumor imaging studies including: CT or MRI, and MIBG scan (or PET if tumor is not MIBG avid) * Bilateral bone marrow aspirates and biopsy Clinical Protocol NMTT NMTRC014 Version 1.0 Issued 12 January 2016 Confidential Page 33 of 65 * This disease assessment is required for eligibility and preferably should be done within 2 weeks prior to enrollment, but must be done within a maximum of 4 weeks before enrollment. 5. Patients who had residual disease prior to post-ASCT radiotherapy must have had re-evaluation of irradiated residual tumors performed no earlier than 5 days after completing radiotherapy. As outlined above, patients with residual disease are eligible if PET negative; confirmation by biopsy is not required. 6. Timing from prior therapy: Stratum 1: Enrollment no later than 60 days after completion of upfront therapy, (last dose of cis-retinoic acid) with a maximum of 6 cycles of cis-retinoic acid maintenance therapy. Stratum 2, 3 and 4: Enrollment no later than 60 days from last dose of the most recent therapy. 7. Patients must have a Lansky or Karnofsky Performance Scale score of >= 50% (see Appendix II) and patients must have a life expectancy of >= 2 months. 8. All clinical and laboratory studies for organ functions to determine eligibility must be performed within 7 days prior to enrollment unless otherwise indicated below. 9. Patients must have adequate organ functions at the time of registration: * Hematological: Total absolute phagocyte count >=1000/[MICRO-SYMBOL]L (APC = (% neutrophils + % bands + % monocytes) x total WBC x 100) * Liver: Subjects must have adequate liver function as defined by AST and ALT <10x upper limit of normal * Renal: Adequate renal function defined as: Creatinine clearance or radioisotope GFR >= 70 mL/min/1.73 m2 or -A serum creatinine based on age/gender 10. Females of childbearing potential must have a negative pregnancy test. Patients of childbearing potential must agree to use an effective birth control method. Female patients who are lactating must agree to stop breast-feeding. 11. Written informed consent in accordance with institutional and FDA guidelines must be obtained from all subjects (or patients[Right Quote] legal representative).
- Cancer Related
- Healthy Volunteers
- UT Southwestern Principal Investigator
- Theodore W Laetsch
NEUROBLASTOMA AND MEDULLOBLASTOMA TRC