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PHASE I PILOT STUDY OF MULTIPLE CYCLES OF HIGH DOSE CHEMOTHERAPY WITH PERIPHERAL BLOOD STEM CELL INFUSIONS IN ADVANCED STAGE NEUROBLASTOMA


Phase 1
1 Year
21 Years
Open (Enrolling)
Both
Neuroblastoma

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Trial Information

PHASE I PILOT STUDY OF MULTIPLE CYCLES OF HIGH DOSE CHEMOTHERAPY WITH PERIPHERAL BLOOD STEM CELL INFUSIONS IN ADVANCED STAGE NEUROBLASTOMA


OBJECTIVES: I. Estimate the maximum tolerated dose of carboplatin that can be given in
combination with cyclophosphamide (CTX) and etoposide following high dose CTX, doxorubicin,
and vincristine in patients with newly diagnosed stage IV neuroblastoma. II. Determine the
hematologic and nonhematologic toxic effects of this regimen in this patient population.
III. Determine the change in neuroblastoma tumor cell content in peripheral blood stem cells
(PBSC) collected following chemotherapy. IV. Assess the feasibility of repetitive
collection, storage, and infusion of PBSC with multicycle high-dose chemotherapy in
pediatric patients. V. Assess hematopoietic recovery following PBSC infusion as well as the
CD34 content and CFU-GM yield of the PBSC products. VI. Assess the response rate and
disease-free survival in the context of a phase I pilot study. VII. Determine the
feasibility of administering twice-daily radiotherapy fractions to post-chemotherapy
residual tumor volumes in neuroblastoma patients.

OUTLINE: This is a dose escalation study of carboplatin. Patients receive induction
chemotherapy consisting of vincristine IV over 24 hours, cyclophosphamide IV over 4 hours,
and doxorubicin IV over 24 hours on days 0, 1, 21, and 22. Patients receive filgrastim
(G-CSF) subcutaneously (SQ) or IV beginning on days 3 and 24 and continuing until blood
counts recover. Patients undergo peripheral blood stem cell (PBSC) collection after course 2
of induction chemotherapy. Patients receive G-CSF SQ or IV for 2 days prior to and during
collection. PBSC are collected daily for 1-3 days. Patients may undergo autologous bone
marrow collection after course 1 of consolidation therapy (after PBSC collection). Following
mobilization, patients receive consolidation chemotherapy consisting of etoposide IV over 4
hours on days 0, 1, and 2 and carboplatin IV over 1 hour and cyclophosphamide IV over 4
hours on days 0 and 1. Patients receive G-CSF SQ or IV beginning on day 3 (within 4 hours of
PBSC infusion) and continuing until blood counts recover. Patients receive PBSC reinfusion
at 48-72 hours following completion of each chemotherapy course. Treatment repeats every 3
weeks for 3 courses in the absence of disease progression or unacceptable toxicity. Upon
recovery from consolidation chemotherapy, patients with no disease progression undergo tumor
resection with or without radiotherapy. Patients undergoing radiotherapy receive therapy
twice daily over 7 days. Patients with no disease progression, less than 2% detectable bone
marrow disease, and adequate bone marrow cellularity may undergo additional therapy
consisting of autologous bone marrow transplantation per appropriate transplant protocol.
Cohorts of 6-12 patients receive escalating doses of carboplatin until the maximum tolerated
dose (MTD) is determined. The MTD is defined as the dose preceding that at which 3 of 6 or 4
of 12 patients experience dose limiting toxicity. Patients are followed every 3 months for 2
years, every 6 months for 3 years, and then annually thereafter.

PROJECTED ACCRUAL: A total of 24-30 patients will be accrued for this study within
approximately 2 years.

Inclusion Criteria


DISEASE CHARACTERISTICS: Newly diagnosed stage IV neuroblastoma by one of the following:
Histologic verification Demonstration of tumor cell clumps in bone marrow with elevated
urinary catecholamine metabolites Initial presentation with low-stage disease allowed if
followed by progression to stage IV disease

PATIENT CHARACTERISTICS: Age: 1 to 21 Performance status: Not specified Hematopoietic:
(unless bone marrow involvement by tumor) Absolute neutrophil count greater than 1,000/mm3
Platelet count greater than 100,000/mm3 Hepatic: Bilirubin less than 3.0 mg/dL Renal:
Creatinine less than 1.5 mg/dL Creatinine clearance or radionuclide GFR greater than 60
mL/min Cardiovascular: EKG normal Ejection fraction at least 55% by radionuclide MUGA OR
Fractional shortening at least 28% by echocardiogram Other: No other significant organ
dysfunction that precludes study treatment Body weight at least 10 kg Not pregnant or
nursing Effective contraception required of fertile patients

PRIOR CONCURRENT THERAPY: No prior systemic chemotherapy No prior radiotherapy except as
emergency treatment

Type of Study:

Interventional

Study Design:

Primary Purpose: Treatment

Principal Investigator

Susan G. Kreissman, MD

Investigator Role:

Study Chair

Investigator Affiliation:

Duke Cancer Institute

Authority:

United States: Federal Government

Study ID:

CDR0000064656

NCT ID:

NCT00002740

Start Date:

May 1996

Completion Date:

Related Keywords:

  • Neuroblastoma
  • disseminated neuroblastoma
  • Neuroblastoma

Name

Location

Indiana University Cancer CenterIndianapolis, Indiana  46202-5265
University of Minnesota Cancer CenterMinneapolis, Minnesota  55455
UCSF Cancer Center and Cancer Research InstituteSan Francisco, California  94115-0128
Children's Hospital Los AngelesLos Angeles, California  90027-0700
Children's Hospital Medical Center - CincinnatiCincinnati, Ohio  45229-3039
Children's Hospital of ColumbusColumbus, Ohio  43205-2696
Children's Hospital and Regional Medical Center - SeattleSeattle, Washington  98105