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Combination Chemotherapy and Peripheral Stem Cell Transplantation in Treating Patients With Neuroblastoma

This study has been completed.
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Children's Oncology Group
ClinicalTrials.gov Identifier:
NCT00004188
First received: January 21, 2000
Last updated: May 16, 2013
Last verified: May 2013
History of Changes
  Purpose

RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining chemotherapy with peripheral stem cell transplantation may allow the doctor to give higher doses of chemotherapy drugs and kill more tumor cells.

PURPOSE: This randomized phase III trial is studying peripheral stem cell transplantation with treated peripheral stem cells following combination chemotherapy to see how well it works compared to peripheral stem cell transplantation with untreated peripheral stem cells following combination chemotherapy in treating patients with neuroblastoma.


Condition Intervention Phase
Neuroblastoma
 Biological: filgrastim
Drug: carboplatin
Drug: cisplatin
Drug: cyclophosphamide
Drug: doxorubicin hydrochloride
Drug: etoposide
Drug: isotretinoin
Drug: melphalan
Drug: topotecan hydrochloride
Drug: vincristine sulfate
Procedure: autologous bone marrow transplantation
Procedure: bone marrow ablation with stem cell support
Procedure: conventional surgery
Procedure: peripheral blood stem cell transplantation
Radiation: radiation therapy
 Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Randomized Study of Purged Versus Unpurged Peripheral Blood Stem Cell Transplant Following Dose Intensive Induction Therapy for High Risk Neuroblastoma

Resource links provided by NLM:

U.S. FDA Resources

Further study details as provided by Children's Oncology Group:

Primary Outcome Measures:
  • Event-free survival rate [ Time Frame: Time from study registration until the time of the first occurrence of either relapse, progression, secondary malignancy, or death, or until the time of last contact with the patient if none of these events occurs, assessed up to 6 years ] [ Designated as safety issue: No ]
  • Rate of occurrence of toxic (non disease-related) deaths where a toxic death will be "counted" if it occurs prior to the initiation of the immunotherapy [ Time Frame: Up to day 42 ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Time to engraftment [ Time Frame: Up to 6 years ] [ Designated as safety issue: No ]
    Engraftment is defined as three consecutive measurements of ANC > 500.

  • CD34 content [ Time Frame: Up to 6 years ] [ Designated as safety issue: No ]
  • Tumor content as measured by reverse transcriptase polymerase chain reaction [ Time Frame: Up to 6 years ] [ Designated as safety issue: No ]

Enrollment: 495
Study Start Date: February 2001
Primary Completion Date: October 2007 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm I (unpurged PBSC collection)
Induction-3 wks (cyclophosphamide day 0&1, doxorubicin hydrochloride & vincristine sulfate day 0-2 & filgrastim(G-CSF) day 3 crs 1,2,4 & 6.) Crs 3 & 5 (etoposide day 0-2, cisplatin day 0-3, G-CSF day 4). Pts undergo unpurged PBSC collection until the target cell count is reached. Surgical resection of the tumor after crs 5 of induct. CR, VGPR, PR after induct receive consolidation (melphalan day -7 to -5, carboplatin & etoposide day -7 to -4. purged peripheral blood stem cell transplantation infusion day 0, G-CSF 4 hrs post transplant. Day 66, isotretinoin 2x day/14 days. Isotretinoin every 4 wks 6 crs. After consol (28 days from stem cell infusion), radiation therapy 1x day/7 days. Not undergoing autologous bone marrow transplantation receive maintenance(cyclophosphamide 30 mins, topotecan hydrochloride days 0-4, G-CSF day 5). Maint every 3 wks/3 crs. Radiation therapy and Isotretinoin 2x day/14 days then every 4 wks for 6 crs.
 Biological: filgrastim
Given IV
Other Names:
  • GRANULOCYTE COLONY-STIMULATING FACTOR
  • r-metHuG-CSF
  • G-CSF
  • Neupogen
  • NSC 614629
Drug: carboplatin
Given IV
Other Names:
  • Paraplatin
  • NSC #241240
Drug: cisplatin
Given IV
Other Names:
  • Cis-diamminedichloroplatinum II
  • Platinol-AQ
  • NSC #11987
Drug: cyclophosphamide
Given IV
Other Names:
  • CTX
  • Cytoxan
  • NSC #026271
Drug: doxorubicin hydrochloride
Given IV
Other Names:
  • Adriamycin
  • NSC #123127
  • IND #7038
Drug: etoposide
Given IV
Other Names:
  • VP-16
  • VePesid
  • Etopophos
  • NSC #141540
Drug: isotretinoin
Given IV
Other Names:
  • 13-cis-retinoic acid
  • RO-43
  • 780
  • Accutane
  • Amnesteem
  • Claravis
  • NSC 329481
Drug: melphalan
Given IV
Other Names:
  • L-phenylalanine mustard
  • phenylalanine mustard
  • L-PAM
  • L-sarcolysin
  • NSC 008806
Drug: topotecan hydrochloride
Given IV
Other Names:
  • SKF-104864
  • Hycamtin
  • NSC #609699
Drug: vincristine sulfate
Given IV
Other Names:
  • VCR
  • Oncovin
  • NSC #067574
Procedure: autologous bone marrow transplantation Procedure: bone marrow ablation with stem cell support Procedure: conventional surgery
All patients undergo delayed surgical resection of the residual tumor after course 5 of induction chemotherapy
Procedure: peripheral blood stem cell transplantation Radiation: radiation therapy
After completion of consolidation (at least 28 days from stem cell infusion), all patients receive local radiotherapy daily over 7 days
Experimental: Arm II (unpurged PBSC collection)
Induction-3 wks (cyclophosphamide day 0&1, doxorubicin hydrochloride & vincristine sulfate day 0-2 & filgrastim(G-CSF) day 3 crs 1,2,4 & 6.) Crs 3 & 5 (etoposide day 0-2, cisplatin day 0-3, G-CSF day 4). Immunocytology + PBSC undergo purged autologous bone marrow collection or repeat purged or unpurged PBSC collection. Surgical resection of the tumor after crs 5 of induct. CR, VGPR, PR after induct receive consolidation (melphalan day -7 to -5, carboplatin & etoposide day -7 to -4. Unpurged peripheral blood stem cell transplantation infusion day 0, G-CSF 4 hrs post transplant. Day 66, isotretinoin 2x day/14 days. Isotretinoin every 4 wks 6 crs. After consol (28 days from stem cell infusion), radiation therapy 1x day/7 days. Not undergoing autologous bone marrow transplantation receive maintenance(cyclophosphamide 30 mins, topotecan hydrochloride days 0-4, G-CSF day 5). Maint every 3 wks/3 crs. Radiation therapy and Isotretinoin 2x day/14 days then every 4 wks for 6 crs.
 Drug: carboplatin
Given IV
Other Names:
  • Paraplatin
  • NSC #241240
Drug: cisplatin
Given IV
Other Names:
  • Cis-diamminedichloroplatinum II
  • Platinol-AQ
  • NSC #11987
Drug: cyclophosphamide
Given IV
Other Names:
  • CTX
  • Cytoxan
  • NSC #026271
Drug: doxorubicin hydrochloride
Given IV
Other Names:
  • Adriamycin
  • NSC #123127
  • IND #7038
Drug: etoposide
Given IV
Other Names:
  • VP-16
  • VePesid
  • Etopophos
  • NSC #141540
Drug: isotretinoin
Given IV
Other Names:
  • 13-cis-retinoic acid
  • RO-43
  • 780
  • Accutane
  • Amnesteem
  • Claravis
  • NSC 329481
Drug: melphalan
Given IV
Other Names:
  • L-phenylalanine mustard
  • phenylalanine mustard
  • L-PAM
  • L-sarcolysin
  • NSC 008806
Drug: topotecan hydrochloride
Given IV
Other Names:
  • SKF-104864
  • Hycamtin
  • NSC #609699
Drug: vincristine sulfate
Given IV
Other Names:
  • VCR
  • Oncovin
  • NSC #067574
Procedure: autologous bone marrow transplantation Procedure: bone marrow ablation with stem cell support Procedure: conventional surgery
All patients undergo delayed surgical resection of the residual tumor after course 5 of induction chemotherapy
Procedure: peripheral blood stem cell transplantation Radiation: radiation therapy
After completion of consolidation (at least 28 days from stem cell infusion), all patients receive local radiotherapy daily over 7 days

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   up to 30 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

DISEASE CHARACTERISTICS:

  • Histologically confirmed newly diagnosed neuroblastoma OR ganglioneuroblastoma, and/or evidence of clumps of tumor cells in bone marrow with elevated urinary catecholamine metabolites, meeting 1 of the following criteria:

    • Age greater than 18 months with stage IV disease, regardless of biologic factors

    • Age 12-18 months with stage IV disease meeting one of the following criteria:

      • Any unfavorable biologic feature (e.g., MYCN amplification, unfavorable pathology, and/or DNA index = 1)
      • Any biologic feature that is indeterminate, unsatisfactory, or unknown

  • At least 1 year old with the following:

    • Stage IIa/IIb with MYCN amplification (> 10) AND unfavorable pathology
    • Stage III with MYCN amplification (> 10) OR unfavorable pathology

    • Stage I, II, or IVS with disease progression to stage IV without interval chemotherapy

      • No more than 3 weeks since progression
      • Must have been enrolled on protocol CCG-B973, COG-ANBL00B1, or POG-9047

  • Less than 1 year old with the following:

    • Stage III, IV, or IVS disease with MYCN amplification (> 10)
  • Registration on protocol COG-ANBL00B1 required within 14 days of diagnosis

PATIENT CHARACTERISTICS:

Age:

  • See Disease Characteristics
  • 30 and under at time of diagnosis

Performance status:

  • Not specified

Life expectancy:

  • Not specified

Hematopoietic:

  • Absolute neutrophil count ≥ 1,000/mm^3
  • Platelet count ≥ 100,000/mm^3
  • Inadequate hematopoiesis secondary to bone marrow involvement with > 10% tumor infiltration allowed

Hepatic:

  • Bilirubin ≤ 1.5 mg/dL
  • ALT ≤ 300 units/L

Renal:

  • Creatinine ≤ 1.5 mg/dL
  • Creatinine clearance or glomerular filtration rate ≥ 60 mL/min

Cardiovascular:

  • ECG normal
  • Ejection fraction ≥ 55% by echocardiogram or MUGA OR
  • Fractional shortening ≥ 28% by echocardiogram

Other:

  • Able to tolerate peripheral blood stem cell collection
  • HIV negative
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception for at least 1 month prior to, during, and for 1 month after study participation

PRIOR CONCURRENT THERAPY:

Biologic therapy:

  • Not specified

Chemotherapy:

  • See Disease Characteristics
  • No more than 1 prior course of chemotherapy on the Intergroup low/intermediate risk neuroblastoma study (P9641, A3961)

Endocrine therapy:

  • Not specified

Radiotherapy:

  • Prior localized emergency radiotherapy to sites of life-threatening or function-threatening disease allowed

Surgery:

  • Not specified

Other

  • No other prior systemic therapy
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00004188

  Show 96 Study Locations
Sponsors and Collaborators
Children's Oncology Group
National Cancer Institute (NCI)
Investigators
Study Chair: Susan G. Kreissman, MD Duke Cancer Institute
  More Information

Additional Information:
Clinical trial summary from the National Cancer Institute's PDQ® database  This link exits the ClinicalTrials.gov site

Publications:
Yanik GA, Parisi MT, Naranjo A, et al.: MIBG scoring as a prognostic indicator in patients with stage IV neuroblastoma: A COG study. [Abstract] J Clin Oncol 28 (Suppl 15): A-9516, 2010.
Kreissman SG, Villablanca JG, Diller L, et al.: Response and toxicity to a dose-intensive multi-agent chemotherapy induction regimen for high risk neuroblastoma (HR-NB): a Children's Oncology Group (COG A3973) study. [Abstract] J Clin Oncol 25 (Suppl 18): A-9505, 527s, 2007.

Responsible Party: Children's Oncology Group
ClinicalTrials.gov Identifier: NCT00004188     History of Changes
Other Study ID Numbers: A3973, COG-A3973, CCG-A3973, POG-A3973, CCG-39703, FHCRC-1631.00, CDR0000067429
Study First Received: January 21, 2000
Last Updated: May 16, 2013
Health Authority: United States: Federal Government

Keywords provided by Children's Oncology Group:
localized resectable neuroblastoma
regional neuroblastoma
disseminated neuroblastoma
stage 4S neuroblastoma
localized unresectable neuroblastoma

Additional relevant MeSH terms:
Neuroblastoma
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
Etoposide phosphate
Cisplatin
Cyclophosphamide
Doxorubicin
Etoposide
 Melphalan
Tretinoin
Vincristine
Carboplatin
Topotecan
Lenograstim
Isotretinoin
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Radiation-Sensitizing Agents
Physiological Effects of Drugs
Immunosuppressive Agents
Immunologic Factors
Antirheumatic Agents

ClinicalTrials.gov processed this record on May 23, 2013