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Clinical Trials (PDQ®)

Busulfan, Melphalan, and Stem Cell Transplant After Chemotherapy in Treating Patients With Newly Diagnosed High-Risk Neuroblastoma

Basic Trial Information
Trial Description
     Summary
     Further Trial Information
     Eligibility Criteria
Trial Contact Information

Basic Trial Information

PhaseTypeStatusAgeSponsorProtocol IDs
No phase specifiedBiomarker/Laboratory analysis, TreatmentTemporarily closed30 and underNCI, OtherANBL12P1
NCI-2012-02211, COG-ANBL12P1, U10CA098543, U10CA180886, NCT01798004

Trial Description

Summary

This pilot clinical trial studies busulfan, melphalan, and stem cell transplant after chemotherapy in treating patients with newly diagnosed neuroblastoma. 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.

Further Study Information

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.

SECONDARY 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.

Eligibility Criteria

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

Trial Contact Information

Trial Lead Organizations/Sponsors

Children's Oncology Group

National Cancer Institute

Mary Meaghan Granger, MDPrincipal Investigator

Trial Sites

U.S.A.
Alabama
  Birmingham
 Children's Hospital of Alabama at University of Alabama at Birmingham
 Alyssa T Reddy Ph: 205-934-0309
California
  Downey
 Southern California Permanente Medical Group
 Robert M Cooper Ph: 626-564-3455
  Duarte
 City of Hope Comprehensive Cancer Center
 Anna B Pawlowska Ph: 800-826-4673
  Email: becomingapatient@coh.org
  Loma Linda
 Loma Linda University Cancer Institute at Loma Linda University Medical Center
 Antranik A Bedros Ph: 909-558-3375
  Los Angeles
 Children's Hospital Los Angeles
 Leo Mascarenhas Ph: 323-361-4110
  Oakland
 Children's Hospital and Research Center Oakland
 Carla B Golden Ph: 510-450-7600
 Kaiser Permanente-Oakland
 Steven K Bergstrom Ph: 626-564-3455
  Orange
 Children's Hospital of Orange County
 Violet Shen Ph: 714-997-3000
  Palo Alto
 Lucile Packard Children's Hospital at Stanford University Medical Center
 Neyssa M Marina Ph: 650-498-7061
  Email: clinicaltrials@med.stanford.edu
  Sacramento
 University of California Davis Cancer Center
 Jay Michael S Balagtas Ph: 916-734-3089
  San Diego
 Rady Children's Hospital - San Diego
 William D Roberts Ph: 858-966-5934
  San Francisco
 UCSF Helen Diller Family Comprehensive Cancer Center
 Steven G DuBois Ph: 877-827-3222
Colorado
  Aurora
 Children's Hospital Colorado Center for Cancer and Blood Disorders
 Brian S Greffe Ph: 720-777-6672
Connecticut
  Hartford
 Connecticut Children's Medical Center
 Michael S Isakoff Ph: 860-545-9981
District of Columbia
  Washington
 Children's National Medical Center
 Jeffrey S Dome Ph: 202-884-2549
 Lombardi Comprehensive Cancer Center at Georgetown University Medical Center
 Aziza T Shad Ph: 202-444-0381
Florida
  Fort Myers
 Children's Hospital of Southwest Florida
 Emad K Salman Ph: 239-343-5333
  Hollywood
 Joe DiMaggio Children's Hospital
 Iftikhar Hanif Ph: 954-265-2234
  Miami
 University of Miami Sylvester Comprehensive Cancer Center - Miami
 Julio C Barredo Ph: 866-574-5124
  Email: Sylvester@emergingmed.com
  Orlando
 Florida Hospital Cancer Institute at Florida Hospital Orlando
 Fouad M Hajjar Ph: 407-303-5623
  Saint Petersburg
 All Children's Hospital
 Gregory A Hale Ph: 727-767-2423
  Email: HamblinF@allkids.org
Georgia
  Atlanta
 AFLAC Cancer Center and Blood Disorders Service of Children's Healthcare of Atlanta - Egleston Campus
 Glen Lew Ph: 404-785-1112
  Augusta
 Medical College of Georgia Cancer Center
 Colleen H McDonough Ph: 706-721-1663
  Email: cancer@georgiahealth.edu
Illinois
  Chicago
 Ann and Robert H. Lurie Children's Hospital of Chicago
 Yasmin C Gosiengfiao Ph: 773-880-4562
 University of Illinois Cancer Center
 Mary L Schmidt Ph: 312-355-3046
  Maywood
 Cardinal Bernardin Cancer Center at Loyola University Medical Center
 Ricarchito B Manera Ph: 708-226-4357
  Springfield
 Simmons Cooper Cancer Institute
 Gregory P Brandt Ph: 217-545-7929
Indiana
  Indianapolis
 Riley's Children Cancer Center at Riley Hospital for Children
 Robert J Fallon Ph: 317-274-2552
 St. Vincent Indianapolis Hospital
 Bassem I Razzouk Ph: 317-338-2194
Iowa
  Des Moines
 Blank Children's Hospital
 Wendy L Woods-Swafford Ph: 515-241-6729
Kentucky
  Lexington
 University of Kentucky Chandler Medical Center
 Lars M Wagner Ph: 859-257-3379
  Louisville
 Kosair Children's Hospital
 Alexandra C Cheerva Ph: 866-530-5516
Louisiana
  New Orleans
 Children's Hospital of New Orleans
 Lolie C Yu Ph: 504-894-5377
Maine
  Scarborough
 Maine Children's Cancer Program at Barbara Bush Children's Hospital
 Eric C Larsen Ph: 207-396-8090
  Email: wrighd@mmc.org
Maryland
  Baltimore
 Alvin and Lois Lapidus Cancer Institute at Sinai Hospital
 Joseph M Wiley Ph: 410-601-6120
  Email: pridgely@lifebridgehealth.org
 Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
 Allen R. Chen Ph: 410-955-8804
  Email: jhcccro@jhmi.edu
  Bethesda
 National Naval Medical Center
 Anne B Warwick Ph: 301-319-2100
Massachusetts
  Boston
 Dana-Farber/Harvard Cancer Center at Dana-Farber Cancer Institute
 Carlos Rodriguez-Galindo Ph: 866-790-4500
 Floating Hospital for Children at Tufts - New England Medical Center
 Michael J Kelly Ph: 617-636-5000
  Email: ContactUsCancerCenter@TuftsMedicalCenter.org
 Massachusetts General Hospital
 Howard J Weinstein Ph: 877-726-5130
Michigan
  Ann Arbor
 C.S. Mott Children's Hospital at University of Michigan Medical Center
 Rajen Mody Ph: 800-865-1125
  Detroit
 Wayne State University
 Roland L Chu Ph: 313-576-9363
  Kalamazoo
 Bronson Methodist Hospital
 Katharina E Elliott Ph: 800-227-2345
Minnesota
  Minneapolis
 Children's Hospitals and Clinics of Minnesota - Minneapolis
 Bruce C Bostrom Ph: 612-813-5193
 Masonic Cancer Center at University of Minnesota
 Emily G Greengard Ph: 612-624-2620
  Rochester
 Mayo Clinic Cancer Center
 Carola A. S. Arndt Ph: 507-538-7623
Missouri
  Kansas City
 Children's Mercy Hospital
 Maxine L Hetherington Ph: 816-234-3265
  Saint Louis
 David C. Pratt Cancer Center at St. John's Mercy
 Bethany G. Sleckman Ph: 913-948-5588
 Siteman Cancer Center at Barnes-Jewish Hospital - Saint Louis
 Shalini Shenoy Ph: 800-600-3606
  Email: info@siteman.wustl.edu
Nebraska
  Omaha
 Children's Hospital
 Minnie Abromowitch Ph: 402-955-3949
 UNMC Eppley Cancer Center at the University of Nebraska Medical Center
 Peter F Coccia Ph: 800-999-5465
Nevada
  Las Vegas
 Cancer Institute of Nevada at Summerlin Hospital Medical Center
 Jonathan Bernstein Ph: 702-384-0013
 CCOP - Nevada Cancer Research Foundation
 Jonathan Bernstein Ph: 702-384-0013
 Children's Specialty Center of Nevada
 Jonathan Bernstein Ph: 702-384-0013
New Hampshire
  Lebanon
 Norris Cotton Cancer Center at Dartmouth-Hitchcock Medical Center
 Sara Chaffee Ph: 800-639-6918
  Email: cancer.research.nurse@dartmouth.edu
New Jersey
  Hackensack
 Hackensack University Medical Center Cancer Center
 Burton E Appel Ph: 201-996-2879
  Morristown
 Carol G. Simon Cancer Center at Morristown Memorial Hospital
 Steven L Halpern Ph: 973-971-5900
  New Brunswick
 Cancer Institute of New Jersey at UMDNJ - Robert Wood Johnson Medical School
 Richard A Drachtman Ph: 732-235-8675
  Newark
 Newark Beth Israel Medical Center
 Peri Kamalakar Ph: 973-926-7230
  Paterson
 St. Joseph's Hospital and Medical Center
 Mary A Bonilla Ph: 973-754-2909
New Mexico
  Albuquerque
 University of New Mexico Cancer Center
 Koh B Boayue Ph: 505-272-6972
New York
  Bronx
 Montefiore Medical Center
 Peter D Cole Ph: 718-904-2730
  Email: aecc@aecom.yu.edu
  Mineola
 Winthrop University Hospital
 Mark E Weinblatt Ph: 866-946-8476
  New Hyde Park
 Schneider Children's Hospital
 Jonathan D Fish Ph: 718-470-3470
  New York
 Herbert Irving Comprehensive Cancer Center at Columbia University Medical Center
 Alice Lee Ph: 212-305-8615
  Rochester
 James P. Wilmot Cancer Center at University of Rochester Medical Center
 Jeffrey R Andolina Ph: 585-275-5830
  Syracuse
 SUNY Upstate Medical University Hospital
 Karol H Kerr Ph: 315-464-5476
North Carolina
  Asheville
 Mission Hospitals - Memorial Campus
 Douglas J Scothorn Ph: 828-213-4150
  Chapel Hill
 Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel Hill
 Stuart H Gold Ph: 877-668-0683
  Email: cancerclinicaltrials@med.unc.edu
Ohio
  Cleveland
 Cleveland Clinic Taussig Cancer Center
 Margaret C Thompson Ph: 866-223-8100
 Seidman Cancer Center at University Hospitals/Case Medical Center
 Yousif (Joe) H Matloub Ph: 216-844-5437
  Columbus
 Nationwide Children's Hospital
 Mark A Ranalli Ph: 614-722-2708
  Dayton
 Dayton Children's - Dayton
 Emmett H Broxson Ph: 800-228-4055
  Toledo
 Toledo Hospital
 Jamie L Dargart Ph: 419-824-1842
Oklahoma
  Oklahoma City
 Oklahoma University Cancer Institute
 Rene Y McNall-Knapp Ph: 405-271-4272
  Email: julie-traylor@ouhsc.edu
Pennsylvania
  Bethlehem
 Lehigh Valley Hospital - Muhlenberg
 Philip M Monteleone Ph: 484-884-2201
  Philadelphia
 Children's Hospital of Philadelphia
 Rochelle Bagatell Ph: 215-590-2810
  Pittsburgh
 Children's Hospital of Pittsburgh of UPMC
 Jean M Tersak Ph: 412-692-5573
South Carolina
  Charleston
 Hollings Cancer Center at Medical University of South Carolina
 Jacqueline M Kraveka Ph: 843-792-9321
  Columbia
 Palmetto Health South Carolina Cancer Center
 Ronnie W. Neuberg Ph: 803-434-3680
Texas
  Dallas
 Simmons Comprehensive Cancer Center at University of Texas Southwestern Medical Center - Dallas
 Tanya C Watt Ph: 214-648-7097
  Houston
 Dan L. Duncan Cancer Center at Baylor College of Medicine
 Timothy C Griffin Ph: 800-284-7370
  San Antonio
 University of Texas Health Science Center at San Antonio
 Anne-Marie R Langevin Ph: 210-450-3800
  Email: CTO@uthscsa.edu
Virginia
  Portsmouth
 Naval Medical Center - Portsmouth
 Bethany M Mikles Ph: 757-953-5939
  Richmond
 Virginia Commonwealth University Massey Cancer Center
 Christina M Wiedl Ph: 804-628-1939
Washington
  Seattle
 Children's Hospital and Regional Medical Center - Seattle
 Douglas S Hawkins Ph: 866-987-2000
  Spokane
 Providence Cancer Center at Sacred Heart Medical Center
 Judy L Felgenhauer Ph: 800-228-6618
  Email: HopeBeginsHere@providence.org
Wisconsin
  Madison
 University of Wisconsin Paul P. Carbone Comprehensive Cancer Center
 Kenneth B DeSantes Ph: 608-262-5223
  Marshfield
 Marshfield Clinic - Marshfield Center
 Michael J McManus Ph: 715-389-4457
Canada
British Columbia
  Vancouver
 Children's and Women's Hospital of British Columbia
 Caron Strahlendorf Ph: 604-875-2345ext6477
Nova Scotia
  Halifax
 IWK Health Centre
 Conrad V Fernandez Ph: 902-470-8394

Link to the current ClinicalTrials.gov record.
NLM Identifer NCT01798004
ClinicalTrials.gov processed this data on October 20, 2014

Note: Information about this trial is from the ClinicalTrials.gov database. The versions designated for health professionals and patients contain the same text. Minor changes may be made to the ClinicalTrials.gov record to standardize the names of study sponsors, sites, and contacts. Cancer.gov only lists sites that are recruiting patients for active trials, whereas ClinicalTrials.gov lists all sites for all trials. Questions and comments regarding the presented information should be directed to ClinicalTrials.gov.

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