Neuroblastoma Maintenance Therapy Trial
Purpose
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 750 mg/m2 ± 250 mg/m2 BID (strata 1, 2, 3, and 4) OR 2500 mg/m2 BID (stratum 1B) on each day of study. This study will focus on the use of DFMO in high risk neuroblastoma patients that are in remission as a strategy to prevent recurrence.
Condition
- Neuroblastoma
Eligibility
- Eligible Ages
- Between 1 Year and 30 Years
- Eligible Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- All patients must have a pathologically confirmed diagnosis of neuroblastoma, < 30.99 years of age and classified as high risk 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): 1. No evidence of residual disease on scan 2. No evidence of disease metastatic to bone marrow. - Specific Criteria by Stratum: Stratum 1/1B: 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 stem cell transplant and radiotherapy, followed by: immunotherapy with Ch14.18/IL-2/GM-CSF (dinutuximab) and retinoic acid;. All subjects on Stratum 1/B must have also met the following criteria: • A pre-transplant disease status evaluation that met International Neuroblastoma Response Criteria (INRC) for CR (complete response), VGPR (very good partial response), or PR (partial response) 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 transplant 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. 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). - Pre-enrollment tumor survey: Prior to enrollment on this study, a determination of mandatory disease staging must be performed: - Tumor imaging studies including - Bilateral bone marrow aspirates and biopsy - 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. - Timing from prior therapy: Stratum 1/1B: 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. - Patients must have a Lansky or Karnofsky Performance Scale score of > 50% and patients must have a life expectancy of ≥ 2 months. - All clinical and laboratory studies for organ functions to determine eligibility must be performed within 7 days prior to enrollment unless otherwise indicated below. - Patients must have adequate organ functions at the time of registration: - Hematological: Total absolute phagocyte count ≥1000/μL - Liver: Subjects must have adequate liver function - Renal: Adequate renal function - 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. - Written informed consent in accordance with institutional and FDA (food and drug administration) guidelines must be obtained from all subjects (or patients' legal representative).
Exclusion Criteria
- BSA (Body Surface Area) 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.
Study Design
- Phase
- Phase 2
- Study Type
- Interventional
- Allocation
- N/A
- Intervention Model
- Single Group Assignment
- Primary Purpose
- Prevention
- Masking
- None (Open Label)
Arm Groups
| Arm | Description | Assigned Intervention |
|---|---|---|
|
Experimental Difluoromethylornithine (DFMO) |
Subjects will receive 730 Days of oral difluoromethylornithine (DFMO) at a dose of 750 mg/m2 ± 250 mg/m2 BID (strata 1, 2, 3, and 4) OR 2500 mg/m2 BID (stratum 1B) on each day of study. |
|
Recruiting Locations
Kentucky Children's Hospital
Lexington 4297983, Kentucky 6254925
Lexington 4297983, Kentucky 6254925
University of Alabama, Children's of Alabama
Birmingham 4049979, Alabama 4829764
Birmingham 4049979, Alabama 4829764
Arkansas Children's Hospital
Little Rock 4119403, Arkansas 4099753 72202
Little Rock 4119403, Arkansas 4099753 72202
UCSF Benioff Children's Hospital Oakland-
Oakland 5378538, California 5332921
Oakland 5378538, California 5332921
Rady Children's Hospital
San Diego 5391811, California 5332921 92123
San Diego 5391811, California 5332921 92123
Rocky Mountain Pediatric Hematology
Denver 5419384, Colorado 5417618
Denver 5419384, Colorado 5417618
Connecticut Children's Hospital
Hartford 4835797, Connecticut 4831725 06106
Hartford 4835797, Connecticut 4831725 06106
University of Florida
Gainesville 4156404, Florida 4155751 32611
Gainesville 4156404, Florida 4155751 32611
Arnold Palmer Hospital for Children
Orlando 4167147, Florida 4155751 32806
Orlando 4167147, Florida 4155751 32806
All Children's Hospital Johns Hopkins Medicine
St. Petersburg 4171563, Florida 4155751 33701
St. Petersburg 4171563, Florida 4155751 33701
St. Joseph's Children's Hospital
Tampa 4174757, Florida 4155751 33614
Tampa 4174757, Florida 4155751 33614
Augusta University Health
Augusta 4180531, Georgia 4197000
Augusta 4180531, Georgia 4197000
Kapiolani Medical Center for Women and Children
Honolulu 5856195, Hawaii 5855797 96813
Honolulu 5856195, Hawaii 5855797 96813
University of Louisville
Louisville 4299276, Kentucky 6254925
Louisville 4299276, Kentucky 6254925
Helen DeVos Children's Hospital
Grand Rapids 4994358, Michigan 5001836 49503
Grand Rapids 4994358, Michigan 5001836 49503
Children's Hospital and Clinics of Minnesota
Minneapolis 5037649, Minnesota 5037779 55404
Minneapolis 5037649, Minnesota 5037779 55404
Children's Mercy Hospitals and Clinics
Kansas City 4393217, Missouri 4398678 64108
Kansas City 4393217, Missouri 4398678 64108
Gina Martin
St Louis 4407066, Missouri 4398678 63104
St Louis 4407066, Missouri 4398678 63104
Hackensack University Medical Center
Hackensack 5098706, New Jersey 5101760
Hackensack 5098706, New Jersey 5101760
Levine Children's Hospital
Charlotte 4460243, North Carolina 4482348 28204
Charlotte 4460243, North Carolina 4482348 28204
Penn State Milton S. Hershey Medical Center and Children's Hospital
Hershey 5193342, Pennsylvania 6254927 17033
Hershey 5193342, Pennsylvania 6254927 17033
Hasbro Children's Hospital
Providence 5224151, Rhode Island 5224323
Providence 5224151, Rhode Island 5224323
Medical University of South Carolina
Charleston 4574324, South Carolina 4597040 29425
Charleston 4574324, South Carolina 4597040 29425
Monroe Carrell Jr. Children's Hospital at Vanderbilt
Nashville 4644585, Tennessee 4662168 37232
Nashville 4644585, Tennessee 4662168 37232
Dell Children's Blood and Cancer Center
Austin 4671654, Texas 4736286 78723
Austin 4671654, Texas 4736286 78723
Children's Medical Center
Dallas 4684888, Texas 4736286 75235
Dallas 4684888, Texas 4736286 75235
Texas Children's Cancer and Hematology Centers
Houston 4699066, Texas 4736286 77030
Houston 4699066, Texas 4736286 77030
Primary Children's Hospital
Salt Lake City 5780993, Utah 5549030 84113
Salt Lake City 5780993, Utah 5549030 84113
Children's Hospital of The King's Daughters
Norfolk 4776222, Virginia 6254928
Norfolk 4776222, Virginia 6254928
Virginia Commonwealth University
Richmond 4781708, Virginia 6254928
Richmond 4781708, Virginia 6254928
Medical College of Wisconsin
Milwaukee 5263045, Wisconsin 5279468 53226
Milwaukee 5263045, Wisconsin 5279468 53226
More Details
- NCT ID
- NCT02679144
- Status
- Recruiting
- Sponsor
- Giselle Sholler