Neuroblastoma Maintenance Therapy Trial

Neuroblastoma Clinical Trial

— NMTT  

Official title:

NMTT- Neuroblastoma Maintenance Therapy Trial Using Difluoromethylornithine (DFMO)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02679144
• Other study ID #: NMTRC014
• Status: Recruiting
• Phase: Phase 2
• Start date: February 2016
• Est. completion date: February 2033

Study information

• Verified date: April 2024
• Source: Milton S. Hershey Medical Center
• Contact: Genevieve Bergendahl, MSN
• Phone: 7175310003
• Email: gbergendahl[@]pennstatehealth.psu.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 258
• Est. completion date: February 2033
• Est. primary completion date: February 2028
• Accepts healthy volunteers: No
• Gender: All
• Age group: 1 Year to 30 Years

Eligibility

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.

Related Conditions & MeSH terms

• Neuroblastoma

Intervention

Drug:
• 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.

Locations

Country	Name	City	State
Canada	Alberta Children's Hospital	Calgary	Alberta
Canada	Montreal Children's Hospital	Montreal	Quebec
Canada	UHC Sainte-Justine	Montréal	Quebec
Canada	CHUQ	Quebec City	Quebec
Canada	Janesway Children's Health and Rehabilitation Centre	Saint John's	Newfoundland and Labrador
Canada	CIUSSS de l'Estrie-CHUS	Sherbrooke	Quebec
Canada	CancerCare Manitoba	Winnipeg	Manitoba
United States	Augusta University Health	Augusta	Georgia
United States	Dell Children's Blood and Cancer Center	Austin	Texas
United States	University of Alabama, Children's of Alabama	Birmingham	Alabama
United States	St. Lukes	Boise	Idaho
United States	Tufts Medical Center	Boston	Massachusetts
United States	Medical University of South Carolina	Charleston	South Carolina
United States	Levine Children's Hospital	Charlotte	North Carolina
United States	Rebecca McFall	Chicago	Illinois
United States	Cleveland Clinic Children's	Cleveland	Ohio
United States	Nationwide Children's Hospital	Columbus	Ohio
United States	Children's Medical Center	Dallas	Texas
United States	Rocky Mountain Pediatric Hematology	Denver	Colorado
United States	Duke University	Durham	North Carolina
United States	University of Florida	Gainesville	Florida
United States	Helen DeVos Children's Hospital	Grand Rapids	Michigan
United States	Hackensack University Medical Center	Hackensack	New Jersey
United States	Connecticut Children's Hospital	Hartford	Connecticut
United States	Penn State Milton S. Hershey Medical Center and Children's Hospital	Hershey	Pennsylvania
United States	Kapiolani Medical Center for Women and Children	Honolulu	Hawaii
United States	Texas Children's Cancer and Hematology Centers	Houston	Texas
United States	Children's Mercy Hospitals and Clinics	Kansas City	Missouri
United States	Kentucky Children's Hospital	Lexington	Kentucky
United States	Arkansas Children's Hospital	Little Rock	Arkansas
United States	University of Louisville	Louisville	Kentucky
United States	Medical College of Wisconsin	Milwaukee	Wisconsin
United States	Children's Hospital and Clinics of Minnesota	Minneapolis	Minnesota
United States	Monroe Carrell Jr. Children's Hospital at Vanderbilt	Nashville	Tennessee
United States	New York University	New York	New York
United States	Children's Hospital of The King's Daughters	Norfolk	Virginia
United States	UCSF Benioff Children's Hospital Oakland-	Oakland	California
United States	Arnold Palmer Hospital for Children	Orlando	Florida
United States	Randall Children's Hospital	Portland	Oregon
United States	Hasbro Children's Hospital	Providence	Rhode Island
United States	Virginia Commonwealth University	Richmond	Virginia
United States	Gina Martin	Saint Louis	Missouri
United States	All Children's Hospital Johns Hopkins Medicine	Saint Petersburg	Florida
United States	Primary Children's Hospital	Salt Lake City	Utah
United States	Rady Children's Hospital	San Diego	California
United States	St. Joseph's Children's Hospital	Tampa	Florida
United States	University of Massachusetts Medical School Worcester	Worcester	Massachusetts

Sponsors (3)

Lead Sponsor	Collaborator
Giselle Sholler	Beat NB Cancer Foundation, Team Parker for Life

Countries where clinical trial is conducted

United States,  Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of participants with event free survival (EFS) during study.		2 years
Secondary	Length of time that participants experience Overall Survival (OS)		7 years
Secondary	Number of Participants with Adverse Events as a Measure of Safety and Tolerability		2 years
Secondary	Peak Plasma Concentration (Cmax)	Pharmacokinetic assay	1 year
Secondary	Area under the plasma concentration versus time curve (AUC)	Pharmacokinetic assay	1 year
Secondary	Time to reach Peak Plasma Concentration (Tmax)	Pharmacokinetic assay	1 year
Secondary	Number of participants with ODC (Ornithine decarboxylase) single nucleotide polymorphisms.		1 year

External Links

•   Beat Childhood Cancer Consortium Website