Clinical Trials Logo

Clinical Trial Details — Status: Active, not recruiting

Administrative data

NCT number NCT01798004
Other study ID # ANBL12P1
Secondary ID NCI-2012-02211AN
Status Active, not recruiting
Phase Phase 1
First received
Last updated
Start date April 8, 2013

Study information

Verified date March 2024
Source Children's Oncology Group
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial Summary

This pilot clinical trial studies busulfan, melphalan, and stem cell transplant after chemotherapy in treating patients with newly diagnosed neuroblastoma that is likely to come back or spread. Giving chemotherapy to the entire body before a stem cell transplant stops the growth of tumor cells by stopping them from dividing or killing them. After treatment, stem cells are collected from the patient's blood and stored. More chemotherapy or radiation therapy is given to prepare the bone marrow for the stem cell transplant. The stem cells are then returned to the patient to replace the blood-forming cells that were destroyed by the chemotherapy.


Description:

PRIMARY OBJECTIVES: I. To determine if the acute toxicity of an autologous stem cell transplant with a busulfan-melphalan (BuMel) based regimen is tolerable when given as consolidation therapy for high-risk neuroblastoma. EXPLORATORY OBJECTIVES: I. To determine the incidence of non-hematologic organ toxicity (grade 3 and higher) and all cause mortality in patients undergoing autologous stem cell transplant with a BuMel based regimen followed by local radiotherapy for the treatment of high-risk neuroblastoma. II. To describe response rates, event-free survival (EFS), and overall survival (OS) for patients undergoing induction therapy followed by consolidation with myeloablative BuMel preparative regimen and local radiotherapy for the treatment of high-risk neuroblastoma. III. To correlate busulfan pharmacokinetics with non-hematologic toxicity following a BuMel based autologous transplant regimen and event-free survival and overall survival. IV. To determine the feasibility of performing Curie scores in "real time," as assessed by central scan committee review of a 123 I-meta-iodobenzylguanidine (MIBG) scan obtained after cycle 4 of induction therapy. V. To examine the concordance between central reviewers and institutional reviewers in performing Curie scoring at diagnosis and after cycle 4 of induction therapy. VI. To determine the feasibility of detecting aberrations in the anaplastic lymphoma kinase (ALK) gene in tumors obtained at the time of diagnosis in patients with high-risk neuroblastoma. VII. To determine the feasibility of performing molecular profiling of neuroblastoma tumors obtained at the time of diagnosis in patients with high-risk neuroblastoma. VIII. To correlate melphalan pharmacokinetics with non-hematologic toxicity following a BuMel based autologous transplant regimen and event-free survival and overall survival. OUTLINE: INDUCTION THERAPY: COURSES 1-2: Patients receive cyclophosphamide intravenously (IV) over 15-30 minutes, topotecan hydrochloride IV over 30 minutes on days 1-5 and filgrastim subcutaneously (SC) or IV once daily (QD) beginning on day 6. Treatment repeats every 3 weeks for 2 courses. COURSES 3 AND 5: Patients receive cisplatin IV over 1 hour on days 1-4 and etoposide IV over 1-2 hours on days 1-3. Treatment repeats every 3 weeks for 2 courses. COURSE 4: Patients receive cyclophosphamide IV over 1-6 hours on days 1-2, vincristine sulfate IV over 1 minute on days 1-3, doxorubicin hydrochloride IV over 24 hours on days 1-3 and mesna IV over 15-30 minutes on days 1-2. Treatment repeats every 3 weeks for 1 course. Treatment continues in the absence of disease progression or unacceptable toxicity. CONSOLIDATION THERAPY: Beginning 4-8 weeks following the 5th course of induction therapy, patients receive busulfan IV over 3 hours on days -6 to -3 and melphalan IV on day -1. Patients undergo autologous stem cell transplant (ASCT) on day 0 and filgrastim SC or IV beginning on day 0. Some patients also undergo external beam radiation therapy (EBRT) after induction and consolidation. After completion of study treatment, patients are followed up every 3 months for 1 year, and then every 6 months for 4 years.


Recruitment information / eligibility

Status Active, not recruiting
Enrollment 150
Est. completion date
Est. primary completion date July 28, 2015
Accepts healthy volunteers No
Gender All
Age group N/A to 30 Years
Eligibility Inclusion Criteria: - Patients must have a diagnosis of neuroblastoma (International Classification of Diseases for Oncology [ICD-O] morphology 9500/3) or ganglioneuroblastoma (nodular or intermixed) verified by histology or demonstration of clumps of tumor cells in bone marrow with elevated urinary catecholamine metabolites; patients with the following disease stages at diagnosis are eligible, if they meet the other specified criteria - Patients with newly diagnosed neuroblastoma with International Neuroblastoma Staging System (INSS) stage 4 are eligible with the following: - V-myc avian myelocytomatosis viral oncogene neuroblastoma derived homolog (MYCN) amplification (> 4-fold increase in MYCN signals as compared to reference signals), regardless of age or additional biologic features or - Age > 18 months (> 547 days) regardless of biologic features or - Age 12-18 months (365-547 days) with any of the following 3 unfavorable biologic features (MYCN amplification, unfavorable pathology and/or deoxyribonucleic acid [DNA] index = 1) or any biologic feature that is indeterminate/unsatisfactory/unknown - Patients with newly diagnosed neuroblastoma with INSS stage 3 are eligible with the following: - MYCN amplification (> 4-fold increase in MYCN signals as compared to reference signals), regardless of age or additional biologic features or - Age > 18 months (> 547 days) with unfavorable pathology, regardless of MYCN status - Patients with newly diagnosed neuroblastoma with INSS stage 2A/2B with MYCN amplification (> 4-fold increase in MYCN signals as compared to reference signals), regardless of age or additional biologic features - Patients with newly diagnosed neuroblastoma with INSS stage 4S with MYCN amplification (> 4-fold increase in MYCN expression signals as compared to reference signals), regardless of additional biologic features - Patients >= 365 days initially diagnosed with neuroblastoma INSS stage 1, 2, 4S who progressed to a stage 4 without interval chemotherapy; these patients must have been enrolled on ANBL00B1; study enrollment on ANBL12P1 must occur within 4 weeks of progression to stage 4 for INSS stage 1, 2, 4S - Patients must not have had prior systemic therapy except for localized emergency radiation to sites of life-threatening or function-threatening disease and/or no more than 1 cycle of chemotherapy per a low or intermediate risk neuroblastoma regimen (as per P9641, A3961, ANBL0531, or similar) prior to determination of MYCN amplification status and histology - Creatinine clearance or radioisotope glomerular filtration rate (GFR) >= 70 mL/min/1.73 m^2 or a serum creatinine based on age/gender as follows: - Age 1 month to < 6 months: 0.4 mg/dL - Age 6 months to < 1 year: 0.5 mg/dL - Age 1 to < 2 years: 0.6 mg/dL - Age 2 to < 6 years: 0.8 mg/dL - Age 6 to < 10 years: 1 mg/dL - Age 10 to < 13 years: 1.2 mg/dL - Age 13 to < 16 years: 1.5 mg/dL (males), 1.4 mg/dL (females) - Age >= 16 years: 1.7 mg/dL (males), 1.4 mg/dL (females) - Total bilirubin =< 1.5 x upper limit of normal (ULN) for age, and - Serum glutamic oxaloacetic transaminase (SGOT) (aspartate aminotransferase [AST]) or serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) < 10 x ULN for age - Shortening fraction of >= 27% by echocardiogram, or - Ejection fraction of >= 50% by radionuclide evaluation - No known contraindication to peripheral blood stem cell (PBSC) collection; examples of contraindications might be a weight or size less than that determined to be feasible at the collecting institution, or a physical condition that would limit the ability of the child to undergo apheresis catheter placement (if necessary) and/or the apheresis procedure - All patients and/or their parents or legal guardians must sign a written informed consent - All institutional, Food and Drug Administration (FDA), and National Cancer Institute (NCI) requirements for human studies must be met Exclusion Criteria: - Patients that are 12-18 months of age with INSS stage 4 and all 3 favorable biologic features (ie, nonamplified MYCN, favorable pathology, and DNA index > 1) are not eligible - Female patients who are pregnant are ineligible - Lactating females are not eligible unless they have agreed not to breastfeed their infants - Female patients of childbearing potential are not eligible unless a negative pregnancy test result has been obtained - Sexually active patients of reproductive potential are not eligible unless they have agreed to use an effective contraceptive method for the duration of their study participation

Study Design


Intervention

Procedure:
Autologous Hematopoietic Stem Cell Transplantation
Undergo autologous peripheral blood stem cell transplant
Drug:
Busulfan
Given IV
Cisplatin
Given IV
Cyclophosphamide
Given IV
Doxorubicin Hydrochloride
Given IV
Etoposide
Given IV
Radiation:
External Beam Radiation Therapy
Undergo EBRT
Biological:
Filgrastim
Given SC or IV
Other:
Laboratory Biomarker Analysis
Optional correlative studies
Drug:
Melphalan
Given IV
Mesna
Given IV
Procedure:
Peripheral Blood Stem Cell Transplantation
Undergo autologous peripheral blood stem cell transplant
Other:
Pharmacological Study
Correlative studies
Drug:
Topotecan Hydrochloride
Given IV
Vincristine Sulfate
Given IV

Locations

Country Name City State
Australia Princess Margaret Hospital for Children Perth Western Australia
Canada IWK Health Centre Halifax Nova Scotia
Canada McMaster Children's Hospital at Hamilton Health Sciences Hamilton Ontario
Canada Centre Hospitalier Universitaire Sainte-Justine Montreal Quebec
Canada The Montreal Children's Hospital of the MUHC Montreal Quebec
Canada CHU de Quebec-Centre Hospitalier de l'Universite Laval (CHUL) Quebec
Canada Hospital for Sick Children Toronto Ontario
Canada British Columbia Children's Hospital Vancouver British Columbia
Canada CancerCare Manitoba Winnipeg Manitoba
New Zealand Starship Children's Hospital Grafton Auckland
United States University of New Mexico Cancer Center Albuquerque New Mexico
United States C S Mott Children's Hospital Ann Arbor Michigan
United States Mission Hospital Asheville North Carolina
United States Children's Healthcare of Atlanta - Egleston Atlanta Georgia
United States Augusta University Medical Center Augusta Georgia
United States Children's Hospital Colorado Aurora Colorado
United States Johns Hopkins University/Sidney Kimmel Cancer Center Baltimore Maryland
United States Sinai Hospital of Baltimore Baltimore Maryland
United States Walter Reed National Military Medical Center Bethesda Maryland
United States Lehigh Valley Hospital - Muhlenberg Bethlehem Pennsylvania
United States Children's Hospital of Alabama Birmingham Alabama
United States Dana-Farber Cancer Institute Boston Massachusetts
United States Massachusetts General Hospital Cancer Center Boston Massachusetts
United States Tufts Children's Hospital Boston Massachusetts
United States Montefiore Medical Center - Moses Campus Bronx New York
United States UNC Lineberger Comprehensive Cancer Center Chapel Hill North Carolina
United States Medical University of South Carolina Charleston South Carolina
United States T C Thompson Children's Hospital Chattanooga Tennessee
United States Lurie Children's Hospital-Chicago Chicago Illinois
United States University of Chicago Comprehensive Cancer Center Chicago Illinois
United States University of Illinois Chicago Illinois
United States Cincinnati Children's Hospital Medical Center Cincinnati Ohio
United States Cleveland Clinic Foundation Cleveland Ohio
United States Rainbow Babies and Childrens Hospital Cleveland Ohio
United States Columbia Regional Columbia Missouri
United States Prisma Health Richland Hospital Columbia South Carolina
United States Nationwide Children's Hospital Columbus Ohio
United States UT Southwestern/Simmons Cancer Center-Dallas Dallas Texas
United States Dayton Children's Hospital Dayton Ohio
United States Blank Children's Hospital Des Moines Iowa
United States Wayne State University/Karmanos Cancer Institute Detroit Michigan
United States Kaiser Permanente Downey Medical Center Downey California
United States City of Hope Comprehensive Cancer Center Duarte California
United States Duke University Medical Center Durham North Carolina
United States Golisano Children's Hospital of Southwest Florida Fort Myers Florida
United States Lee Memorial Health System Fort Myers Florida
United States Cook Children's Medical Center Fort Worth Texas
United States University of Florida Health Science Center - Gainesville Gainesville Florida
United States BI-LO Charities Children's Cancer Center Greenville South Carolina
United States Hackensack University Medical Center Hackensack New Jersey
United States Connecticut Children's Medical Center Hartford Connecticut
United States Memorial Regional Hospital/Joe DiMaggio Children's Hospital Hollywood Florida
United States Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center Houston Texas
United States Ascension Saint Vincent Indianapolis Hospital Indianapolis Indiana
United States Riley Hospital for Children Indianapolis Indiana
United States University of Mississippi Medical Center Jackson Mississippi
United States Nemours Children's Clinic-Jacksonville Jacksonville Florida
United States Bronson Methodist Hospital Kalamazoo Michigan
United States Children's Mercy Hospitals and Clinics Kansas City Missouri
United States East Tennessee Childrens Hospital Knoxville Tennessee
United States Alliance for Childhood Diseases/Cure 4 the Kids Foundation Las Vegas Nevada
United States Nevada Cancer Research Foundation NCORP Las Vegas Nevada
United States Summerlin Hospital Medical Center Las Vegas Nevada
United States Dartmouth Hitchcock Medical Center/Dartmouth Cancer Center Lebanon New Hampshire
United States University of Kentucky/Markey Cancer Center Lexington Kentucky
United States Saint Barnabas Medical Center Livingston New Jersey
United States Loma Linda University Medical Center Loma Linda California
United States Children's Hospital Los Angeles Los Angeles California
United States Norton Children's Hospital Louisville Kentucky
United States University of Wisconsin Carbone Cancer Center Madison Wisconsin
United States Marshfield Medical Center-Marshfield Marshfield Wisconsin
United States Loyola University Medical Center Maywood Illinois
United States Miami Cancer Institute Miami Florida
United States University of Miami Miller School of Medicine-Sylvester Cancer Center Miami Florida
United States NYU Winthrop Hospital Mineola New York
United States Children's Hospitals and Clinics of Minnesota - Minneapolis Minneapolis Minnesota
United States University of Minnesota/Masonic Cancer Center Minneapolis Minnesota
United States Morristown Medical Center Morristown New Jersey
United States Vanderbilt University/Ingram Cancer Center Nashville Tennessee
United States Rutgers Cancer Institute of New Jersey-Robert Wood Johnson University Hospital New Brunswick New Jersey
United States The Steven and Alexandra Cohen Children's Medical Center of New York New Hyde Park New York
United States Children's Hospital New Orleans New Orleans Louisiana
United States NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center New York New York
United States Newark Beth Israel Medical Center Newark New Jersey
United States Kaiser Permanente-Oakland Oakland California
United States UCSF Benioff Children's Hospital Oakland Oakland California
United States University of Oklahoma Health Sciences Center Oklahoma City Oklahoma
United States Children's Hospital and Medical Center of Omaha Omaha Nebraska
United States University of Nebraska Medical Center Omaha Nebraska
United States Children's Hospital of Orange County Orange California
United States AdventHealth Orlando Orlando Florida
United States Nemours Children's Hospital Orlando Florida
United States Lucile Packard Children's Hospital Stanford University Palo Alto California
United States Saint Joseph's Regional Medical Center Paterson New Jersey
United States Nemours Children's Clinic - Pensacola Pensacola Florida
United States Saint Jude Midwest Affiliate Peoria Illinois
United States Children's Hospital of Philadelphia Philadelphia Pennsylvania
United States Children's Hospital of Pittsburgh of UPMC Pittsburgh Pennsylvania
United States Naval Medical Center - Portsmouth Portsmouth Virginia
United States Virginia Commonwealth University/Massey Cancer Center Richmond Virginia
United States Mayo Clinic in Rochester Rochester Minnesota
United States University of Rochester Rochester New York
United States University of California Davis Comprehensive Cancer Center Sacramento California
United States Mercy Hospital Saint Louis Saint Louis Missouri
United States Washington University School of Medicine Saint Louis Missouri
United States Johns Hopkins All Children's Hospital Saint Petersburg Florida
United States Methodist Children's Hospital of South Texas San Antonio Texas
United States University of Texas Health Science Center at San Antonio San Antonio Texas
United States Rady Children's Hospital - San Diego San Diego California
United States UCSF Medical Center-Mission Bay San Francisco California
United States UCSF Medical Center-Parnassus San Francisco California
United States Memorial Health University Medical Center Savannah Georgia
United States Maine Children's Cancer Program Scarborough Maine
United States Seattle Children's Hospital Seattle Washington
United States Providence Sacred Heart Medical Center and Children's Hospital Spokane Washington
United States Southern Illinois University School of Medicine Springfield Illinois
United States State University of New York Upstate Medical University Syracuse New York
United States Saint Joseph's Hospital/Children's Hospital-Tampa Tampa Florida
United States Mercy Children's Hospital Toledo Ohio
United States ProMedica Toledo Hospital/Russell J Ebeid Children's Hospital Toledo Ohio
United States Children's National Medical Center Washington District of Columbia
United States MedStar Georgetown University Hospital Washington District of Columbia
United States Alfred I duPont Hospital for Children Wilmington Delaware

Sponsors (2)

Lead Sponsor Collaborator
Children's Oncology Group National Cancer Institute (NCI)

Countries where clinical trial is conducted

United States,  Australia,  Canada,  New Zealand, 

Outcome

Type Measure Description Time frame Safety issue
Other Incidence of Non-hematologic Organ Toxicity (Grade 3 and Higher) and All Cause Mortality Graded According to CTC v4.0 Assessed by a descriptive analysis of the incidence of grade 3-5 non-hematologic toxicities (CTC v4.0) and all-cause mortality during consolidation therapy. In addition, a descriptive analysis of "late" onset grade 4-5 pulmonary and hepatic complications that occur within 180 days of the start of consolidation therapy will be examined, regardless if the patient has proceeded to other therapy (including chimeric antibody) during that 180 day period. Up to 180 days
Other Response Rate Determined Using the International Response Criteria Up to 5 years
Other EFS Up to 5 years
Other Overall Survival Up to 5 years
Other First Dose Area Under the Curve (AUC) and Average Daily AUC for Busulfan Relationship with occurrence of non-hematologic toxicities assessed by a descriptive analysis. Association between busulfan exposure levels as measured by the area under the curve (AUC) and event-free survival and overall survival will be examined using Cox proportional hazards models. Within 28 days following consolidation
Other Percentage of Centrally Reviewed Post-course 4 MIBG Scans Reporting a Curie Score Considered to Have Been Determined in "Real Time" Up to week 12 (course 4 of induction therapy)
Other Percentage of MIBG Scans Receiving Institutionally and Centrally Reviewed and Automated Advanced Assisted Scoring Platform Curie Scores Within 1 Unit of Each Other Cohen's kappa will be calculated to evaluate the concordance in Curie scores between each of the scoring methods at each time point. Up to 160 MIBG scans are expected at diagnosis and up to 144 MIBG scans from the 90% of patients estimated to be MIBG avid are projected post-course 4 of induction therapy, for a total of up to 304 MIBG scans. Up to week 12 (course 4 of induction therapy)
Other Proportion of High-risk Neuroblastoma Patients for Whom ALK Status Can be Obtained Within 6 weeks of diagnosis
Other Proportion of High-risk Neuroblastoma Patients With MYCN Non-amplified Tumors for Whom Molecular Profiling Results Can be Obtained Within 8 weeks of diagnosis
Other Melphalan Pharmacokinetics and the Combination of Busulfan and Melphalan AUC (Optional) A descriptive analysis of the relationship between melphalan pharmacokinetics and the combination of busulfan and melphalan AUC with the occurrence of non-hematologic toxicities within 28 days following completion of consolidation will be assessed. In addition, the association between melphalan exposure levels as measured by the AUC and event-free survival and overall survival will be examined using Cox proportional hazards models. Within 28 days post-consolidation
Primary The Tolerability of BuMel Regimen Number of patients who experience one or more unacceptable toxicities (severe sinusoidal obstruction syndrome [SOS] or Grade 4-5 pulmonary toxicity per Common Toxicity Criteria [CTC] v.4.0) during the Consolidation phase of therapy. Up to 28 days post-consolidation therapy, up to 1 year
See also
  Status Clinical Trial Phase
Recruiting NCT04040088 - An Investigational Scan (68Ga-DOTATATE PET/CT) in Diagnosing Pediatric Metastatic Neuroendocrine Tumors Early Phase 1
Recruiting NCT06071897 - Induction Chemoimmunotherapy for Patients With High-risk Neuroblastoma Phase 3
Active, not recruiting NCT01175356 - Induction Therapy Including 131 I-MIBG and Chemotherapy in Treating Patients With Newly Diagnosed High-Risk Neuroblastoma Undergoing Stem Cell Transplant, Radiation Therapy, and Maintenance Therapy With Isotretinoin Phase 1
Recruiting NCT06296732 - Abdominal Neuroblastoma Laparoscopic Surgery Risk Factors Stratification
Recruiting NCT00904241 - Biomarkers in Tumor Tissue Samples From Patients With Newly Diagnosed Neuroblastoma or Ganglioneuroblastoma
Active, not recruiting NCT02311621 - Engineered Neuroblastoma Cellular Immunotherapy (ENCIT)-01 Phase 1
Recruiting NCT05192980 - SIOPEN BIOPORTAL, An International Registry Linked to a Virtual Biobank for Patients With Peripheral Neuroblastic Tumours N/A
Active, not recruiting NCT03126916 - Testing the Addition of 131I-MIBG or Lorlatinib to Intensive Therapy in People With High-Risk Neuroblastoma (NBL) Phase 3
Active, not recruiting NCT03786783 - Dinutuximab, Sargramostim, and Combination Chemotherapy in Treating Patients With Newly Diagnosed High-Risk Neuroblastoma Phase 2
Recruiting NCT02112617 - Phase II Study of Proton Radiation Therapy for Neuroblastoma N/A
Completed NCT01767194 - Irinotecan Hydrochloride and Temozolomide With Temsirolimus or Dinutuximab in Treating Younger Patients With Refractory or Relapsed Neuroblastoma Phase 2
Active, not recruiting NCT02176967 - Response and Biology-Based Risk Factor-Guided Therapy in Treating Younger Patients With Non-high Risk Neuroblastoma Phase 3