Comparing Two Different Myeloablation Therapies in Treating Young Patients Who Are Undergoing a Stem Cell Transplant for High-Risk Neuroblastoma

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Children's Oncology Group
ClinicalTrials.gov Identifier:
NCT00567567
First received: December 4, 2007
Last updated: May 13, 2013
Last verified: May 2013
  Purpose

RATIONALE: Drugs used in chemotherapy work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving combination chemotherapy before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed. Radiation therapy uses high-energy x-rays to kill tumor cells. Giving radiation therapy after surgery may kill any tumor cells that remain after surgery. It is not yet known which regimen of myeloablation chemotherapy is more effective for patients with high-risk neuroblastoma undergoing a peripheral blood stem cell transplant.

PURPOSE: This randomized phase III trial is comparing two different myeloablation therapies followed by a stem cell transplant in treating young patients with high-risk neuroblastoma.


Condition Intervention Phase
Neuroblastoma
Drug: carboplatin
Drug: cyclophosphamide
Drug: etoposide
Drug: melphalan
Drug: thiotepa
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase III Randomized Trial of Single vs. Tandem Myeloablative Consolidation Therapy for High-Risk Neuroblastoma

Resource links provided by NLM:


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

Primary Outcome Measures:
  • Event-free survival rate [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]
    Intent-to-treat log-rank test comparison of EFS curves, starting from the time of randomization, by treatment group (AT-CEM vs. AT1-TC & AT2-CEM). Kaplan-Meier curves will be generated starting from a) the time of randomization (this is the definitive analysis); b) the time of transplant; c) the time of completion of the last transplant (for descriptive purposes); and d) the time of diagnosis (for descriptive purposes).

  • Response after induction therapy [ Time Frame: 126 days ] [ Designated as safety issue: No ]
    Chi-square test of proportions in all patients to compare the proportion of responders (CR+VGPRs) at the end of induction in this study to the analogous proportion in A3973. There is no reason to believe that the characteristics of the induction cohort on this study will differ from that of the induction cohort on A3973, so this will be a fair and appropriate comparison.

  • Incidence rate of local recurrence [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]
    Log-rank test to compare the risk for local recurrence within the subset of patients who obtain a pre-transplant primary site < CR, i.e., comparing ANBL0532 patients randomized to get one transplant versus the historical A3973 patients who were randomized to unpurged transplant.


Secondary Outcome Measures:
  • Duration of ≥ grade 3 neutropenia during course one [ Time Frame: 21 days ] [ Designated as safety issue: No ]
    A logistic regression model will be used to test the ability of the number of days of neutropenia to predict the presence of a polymorphism.

  • Duration of ≥ grade 3 thrombocytopenia during course one [ Time Frame: 21 days ] [ Designated as safety issue: No ]
    A logistic regression model will be used to test the ability of the number of days of thrombocytopenia to predict the presence of a polymorphism.

  • Response rate after two courses of induction therapy [ Time Frame: 42 days ] [ Designated as safety issue: No ]
    A chi-square test of association will be used to compare the proportion of responders with versus without a polymorphism


Enrollment: 665
Study Start Date: November 2007
Estimated Primary Completion Date: December 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Consolidation therapy arm A
(Single myeloablative consolidation): Patients receive melphalan IV over 15-30 minutes on days -7 to -5, etoposide IV over 24 hours and carboplatin IV over 24 hours on days -7 to -4. Patients undergo autologous PBSCT on day 0.
Drug: carboplatin
Given IV
Other Names:
  • Paraplatin
  • NSC #241240
Drug: etoposide
Given IV
Other Names:
  • VePesid
  • Etopophos
  • VP-16
  • NSC #141540
Drug: melphalan
Given IV
Other Names:
  • L-phenylalanine mustard
  • phenylalanine mustard
  • L-PAM
  • L-sarcolysin
  • Alkeran
  • NSC #0088
Experimental: Consolidation therapy arm B
(Tandem myeloablative consolidation): Patients receive thiotepa IV over 2 hours on days -7 to -5, cyclophosphamide IV over 1 hour on days -5 to -2. Following recover from this therapy, patients also receive melphalan, etoposide, and carboplatin as in arm A. Patients undergo autologous PBSCT on day 0.
Drug: carboplatin
Given IV
Other Names:
  • Paraplatin
  • NSC #241240
Drug: cyclophosphamide
Given IV
Other Names:
  • Cytoxan
  • NSC #26271
Drug: etoposide
Given IV
Other Names:
  • VePesid
  • Etopophos
  • VP-16
  • NSC #141540
Drug: melphalan
Given IV
Other Names:
  • L-phenylalanine mustard
  • phenylalanine mustard
  • L-PAM
  • L-sarcolysin
  • Alkeran
  • NSC #0088
Drug: thiotepa
Given IV
Other Names:
  • Tepadina
  • Tespa
  • Thiophosphamide
  • Triethylenethiophosphoramide Tspa
  • WR-45312
  • NSC 6396

  Show Detailed Description

  Eligibility

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

DISEASE CHARACTERISTICS:

  • Diagnosis of neuroblastoma or ganglioneuroblastoma by histology or as evidenced by the presence of clumps of tumor cells in bone marrow and elevated catecholamine metabolites in urine meeting any of the following criteria:

    • Patients with newly diagnosed neuroblastoma with International Neuroblastoma Staging System (INSS) stage 4 disease are eligible with the following:

      • MYCN amplification (i.e., greater than four-fold increase in MYCN signals as compared to reference signals), regardless of age or additional biologic features
      • Age > 18 months (i.e., > 547 days) regardless of biologic features
      • Age 12-18 months (i.e., 365-547 days) with none of the following three favorable biologic features (i.e., non-amplified MYCN, favorable pathology, and DNA index > 1)
    • Patients with newly diagnosed neuroblastoma with INSS stage 3 are eligible with the following:

      • MYCN amplification (i.e., greater than four-fold increase in MYCN signals as compared to reference signals), regardless of age or additional biologic features
      • Age > 18 months (i.e., > 547 days) with unfavorable pathology, regardless of MYCN status
    • Patients with newly diagnosed INSS stage 2a or 2b with MYCN amplification (i.e., greater than four-fold increase in MYCN signals as compared to reference signals), regardless of age or additional biologic features
    • Patients with newly diagnosed INSS stage 4s with MYCN amplification (i.e., greater than four-fold increase in MYCN signals as compared to reference signals), regardless of additional biologic features
    • Patients ≥ 365 days initially diagnosed with INSS stage 1, 2, or 4S and who progressed to a stage 4 without interval chemotherapy

      • Must have been enrolled on COG-ANBL00B1

PATIENT CHARACTERISTICS:

  • Creatinine clearance or radioisotope glomerular filtration rate ≥ 70mL/min OR serum creatinine based on age/gender as follows:

    • 1 month to < 6 months: 0.4 mg/dL
    • 6 months to < 1 year: 0.5 mg/dL
    • 1 to < 2 years: 0.6 mg/dL
    • 2 to < 6 years: 0.8 mg/dL
    • 6 to < 10 years: 1 mg/dL
    • 10 to < 13 years: 1.2 mg/dL
    • 10 to < 16 years: 1.5 mg/dL (male), 1.4 mg/dL (female)
    • ≥ 16 years: 1.7 mg/dL (male), 1.4 mg/dL (female)
  • Total bilirubin ≤ 1.5 times upper limit of normal (ULN) for age
  • AST or ALT < 10 times ULN for age
  • Not pregnant or nursing
  • Negative pregnancy test
  • Shortening fraction ≥ 27% by ECHO OR LVEF ≥ 50% by radionuclide angiogram
  • No known contraindication (e.g., size, weight or physical condition) to peripheral blood stem cell collection

PRIOR CONCURRENT THERAPY:

  • No prior systemic therapy except for localized emergency radiation to sites of life-threatening or function-threatening disease
  • No more than one course of chemotherapy per low- or intermediate-risk neuroblastoma therapy prior to determination of MYCN amplification and histology
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00567567

  Show 170 Study Locations
Sponsors and Collaborators
Children's Oncology Group
Investigators
Study Chair: Julie R. Park, MD Seattle Children's Hospital
  More Information

Additional Information:
No publications provided

Responsible Party: Children's Oncology Group
ClinicalTrials.gov Identifier: NCT00567567     History of Changes
Other Study ID Numbers: ANBL0532, COG-ANBL0532, CDR0000576571
Study First Received: December 4, 2007
Last Updated: May 13, 2013
Health Authority: United States: Federal Government

Keywords provided by Children's Oncology Group:
disseminated neuroblastoma
localized resectable neuroblastoma
localized unresectable neuroblastoma
recurrent neuroblastoma
regional neuroblastoma
stage 4S 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
Cyclophosphamide
Melphalan
Thiotepa
Etoposide phosphate
Etoposide
Carboplatin
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antirheumatic Agents
Therapeutic Uses
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists
Antineoplastic Agents, Phytogenic

ClinicalTrials.gov processed this record on April 16, 2014