Combination Chemotherapy Plus Peripheral Stem Cell Transplantation in Treating Children With Newly Diagnosed Neuroblastoma

NCT00017368 | Completed Phase 2 DMC

• 3 other identifiers: ANBL00P1COG-ANBL00P1CDR0000068681
• Study Type: interventional
• Target: 42
• Locations: 2 countries
• Sites: 9

Brief Summary

RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining more than one drug may kill more tumor cells. Peripheral stem cell transplantation may allow the doctor to give higher doses of chemotherapy drugs and kill more tumor cells. PURPOSE: Phase II trial to study the effectiveness of combination chemotherapy followed by peripheral stem cell transplantation in treating children who have newly diagnosed neuroblastoma.

Conditions

Neuroblastoma

Keywords

regional neuroblastoma; disseminated neuroblastoma; localized unresectable neuroblastoma; stage 4S neuroblastoma

Outcome Measures

Primary Outcomes (1)

• Transplant-related mortality

  The endpoint used for early stopping rule 9.51 will be transplant-related mortality (TRM). A TRM is defined as any death occurring within 30 days after either the first or second HDC/SCR. The acceptable TRM rate is 7.5%. This rate is based on TRM rates previously observed in the prior CCG study 594, CCG study 3891, and POG study 9640 of 7%, 6%, and 0%, respectively.

Secondary Outcomes (2)

• Incidence of symptomatic CMV, disseminated adenovirus infection, or EBV-LPD

• Event-free Survival

  1 year

Study Arms (1)

All Patients

EXPERIMENTAL

Biological: filgrastim; Biological: sargramostim; Drug: carboplatin; Drug: cisplatin; Drug: cyclophosphamide; Drug: doxorubicin hydrochloride; Drug: etoposide; Drug: etoposide phosphate; Drug: ifosfamide; Drug: isotretinoin; Drug: melphalan; Drug: thiotepa; Drug: vincristine sulfate; Procedure: conventional surgery; Procedure: peripheral blood stem cell transplantation; Radiation: radiation therapy

Interventions

filgrastim BIOLOGICAL

All Patients

sargramostim BIOLOGICAL

All Patients

carboplatin DRUG

All Patients

cisplatin DRUG

All Patients

cyclophosphamide DRUG

All Patients

doxorubicin hydrochloride DRUG

All Patients

etoposide DRUG

All Patients

etoposide phosphate DRUG

All Patients

ifosfamide DRUG

All Patients

isotretinoin DRUG

All Patients

melphalan DRUG

All Patients

thiotepa DRUG

All Patients

vincristine sulfate DRUG

All Patients

conventional surgery PROCEDURE

All Patients

peripheral blood stem cell transplantation PROCEDURE

All Patients

radiation therapy RADIATION

All Patients

Eligibility Criteria

• Age: Up to 30 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

DISEASE CHARACTERISTICS: * Newly diagnosed high-risk neuroblastoma * Histologically proven AND/OR * Bone marrow specimen showing clumps of tumor cells accompanied by elevated urinary catecholamines * Age 1-30: * Must meet one of the following INSS staging criteria: * Stage IV regardless of biologic factors * Stage IIa/IIb with MYCN oncogene amplification (greater than 10) and unfavorable pathology * Stage III with MYCN oncogene amplification (greater than 10) or unfavorable pathology * Initially stage I, II, or IVS, that has progressed without interval chemotherapy * Under age 1: * INSS stage III, IV, or IVS with MYCN amplification (greater than 10) * Must enter neuroblastoma biology study COG-ANBL00B1 within 2 weeks of diagnosis and before entry on this study PATIENT CHARACTERISTICS: Age: * 30 and under at original diagnosis Performance status: * Not specified Life expectancy: * Not specified Hematopoietic: * Not specified Hepatic: * Not specified Renal: * Not specified Other: * Not pregnant or nursing * Fertile patients must use effective contraception PRIOR CONCURRENT THERAPY: Biologic therapy: * Not specified Chemotherapy: * See Disease Characteristics * No more than 1 prior course of chemotherapy on the intergroup low- or intermediate-risk neuroblastoma studies prior to determination of MYCN status and Shimada histology Endocrine therapy: * Not specified Radiotherapy: * Prior emergent radiotherapy to sites of function- or life-threatening neuroblastoma allowed Surgery: * Not specified Other: * No other prior systemic therapy for neuroblastoma

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• Children's Oncology Group: lead
• National Cancer Institute (NCI): collaborator

Study Sites (9)

AFLAC Cancer Center and Blood Disorders Service of Children's Healthcare of Atlanta - Scottish RiteCampus

Atlanta, Georgia, 30342, United States

Location

Floating Hospital for Children

Boston, Massachusetts, 02111, United States

Location

Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute

Boston, Massachusetts, 02115, United States

Location

CCOP - Columbia River Oncology Program

Portland, Oregon, 97225, United States

Location

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, 19104, United States

Location

Baylor College of Medicine

Houston, Texas, 77030, United States

Location

CCOP - Scott and White Hospital

Temple, Texas, 76508, United States

Location

CCOP - Marshfield Clinic Research Foundation

Marshfield, Wisconsin, 54449, United States

Location

Princess Margaret Hospital for Children

Perth, Western Australia, 6001, Australia

Location

Related Publications (5)

• Marcus KJ, Shamberger R, Litman H, von Allmen D, Grupp SA, Nancarrow CM, Goldwein J, Grier HE, Diller L. Primary tumor control in patients with stage 3/4 unfavorable neuroblastoma treated with tandem double autologous stem cell transplants. J Pediatr Hematol Oncol. 2003 Dec;25(12):934-40. doi: 10.1097/00043426-200312000-00005.

  PMID: 14663275 BACKGROUND

• Kletzel M, Katzenstein HM, Haut PR, Yu AL, Morgan E, Reynolds M, Geissler G, Marymount MH, Liu D, Kalapurakal JA, Shore RM, Bardo DM, Schmoldt J, Rademaker AW, Cohn SL. Treatment of high-risk neuroblastoma with triple-tandem high-dose therapy and stem-cell rescue: results of the Chicago Pilot II Study. J Clin Oncol. 2002 May 1;20(9):2284-92. doi: 10.1200/JCO.2002.06.060.

  PMID: 11980999 BACKGROUND

• Donovan J, Temel J, Zuckerman A, Gribben J, Fang J, Pierson G, Ross A, Diller L, Grupp SA. CD34 selection as a stem cell purging strategy for neuroblastoma: preclinical and clinical studies. Med Pediatr Oncol. 2000 Dec;35(6):677-82. doi: 10.1002/1096-911x(20001201)35:63.0.co;2-h.

  PMID: 11107145 BACKGROUND

• Grupp SA, Stern JW, Bunin N, Nancarrow C, Adams R, Gorlin JB, Griffin G, Diller L. Rapid-sequence tandem transplant for children with high-risk neuroblastoma. Med Pediatr Oncol. 2000 Dec;35(6):696-700. doi: 10.1002/1096-911x(20001201)35:63.0.co;2-0.

  PMID: 11107149 BACKGROUND

• Grupp SA, Stern JW, Bunin N, Nancarrow C, Ross AA, Mogul M, Adams R, Grier HE, Gorlin JB, Shamberger R, Marcus K, Neuberg D, Weinstein HJ, Diller L. Tandem high-dose therapy in rapid sequence for children with high-risk neuroblastoma. J Clin Oncol. 2000 Jul;18(13):2567-75. doi: 10.1200/JCO.2000.18.13.2567.

  PMID: 10893288 BACKGROUND

MeSH Terms

Conditions

Neuroblastoma

Interventions

Filgrastim; sargramostim; Carboplatin; Cisplatin; Cyclophosphamide; Doxorubicin; Etoposide; etoposide phosphate; Ifosfamide; Isotretinoin; Melphalan; Thiotepa; Vincristine; Peripheral Blood Stem Cell Transplantation; Radiotherapy

Condition Hierarchy (Ancestors)

Neuroectodermal Tumors, Primitive, Peripheral; Neuroectodermal Tumors, Primitive; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Intervention Hierarchy (Ancestors)

Granulocyte Colony-Stimulating Factor; Colony-Stimulating Factors; Glycoproteins; Glycoconjugates; Carbohydrates; Hematopoietic Cell Growth Factors; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors; Coordination Complexes; Organic Chemicals; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Phosphoramides; Organophosphorus Compounds; Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Polycyclic Compounds; Aminoglycosides; Glycosides; Podophyllotoxin; Tetrahydronaphthalenes; Naphthalenes; Glucosides; Oxazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Retinoids; Carotenoids; Polyenes; Alkenes; Hydrocarbons, Acyclic; Cyclohexenes; Cyclohexanes; Cycloparaffins; Hydrocarbons, Alicyclic; Terpenes; Pigments, Biological; Phenylalanine; Amino Acids, Aromatic; Amino Acids, Cyclic; Amino Acids; Triethylenephosphoramide; Aziridines; Azirines; Vinca Alkaloids; Secologanin Tryptamine Alkaloids; Indole Alkaloids; Alkaloids; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Indolizidines; Indolizines; Hematopoietic Stem Cell Transplantation; Stem Cell Transplantation; Cell Transplantation; Cell- and Tissue-Based Therapy; Biological Therapy; Therapeutics; Transplantation; Surgical Procedures, Operative

Study Officials

• Stephan A. Grupp, MD, PhD

  Children's Hospital of Philadelphia

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 6, 2001
• First Posted: October 9, 2003
• Study Start: April 1, 2001
• Primary Completion: September 1, 2005
• Study Completion: January 1, 2012
• Last Updated: February 13, 2014

Record last verified: 2014-02

Locations

US (8); AU (1)